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1.
J Am Soc Nephrol ; 29(10): 2510-2517, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30206141

RESUMO

BACKGROUND: Renal flow abnormalities are believed to play a central role in the pathogenesis of nephropathy and in primary and secondary hypertension, but are difficult to measure in humans. Handgrip exercise is known to reduce renal arterial flow (RAF) by means of increased renal sympathetic nerve activity. METHODS: To monitor medullary and cortical oxygenation under handgrip exercise-reduced perfusion, we used contrast- and radiation-free magnetic resonance imaging (MRI) to measure regional changes in renal perfusion and blood oxygenation in ten healthy normotensive individuals during handgrip exercise. We used phase-contrast MRI to measure RAF, arterial spin labeling to measure perfusion, and both changes in transverse relaxation time (T2*) and dynamic blood oxygenation level-dependent imaging to measure blood oxygenation. RESULTS: Handgrip exercise induced a significant decrease in RAF. In the renal medulla, this was accompanied by an increase of oxygenation (reflected by an increase in T2*) despite a significant drop in medullary perfusion; the renal cortex showed a significant decrease in both perfusion and oxygenation. We also found a significant correlation (R2=0.8) between resting systolic BP and the decrease in RAF during handgrip exercise. CONCLUSIONS: Renal MRI measurements in response to handgrip exercise were consistent with a sympathetically mediated decrease in RAF. In the renal medulla, oxygenation increased despite a reduction in perfusion, which we interpreted as the result of decreased GFR and a subsequently reduced reabsorptive workload. Our results further indicate that the renal flow response's sensitivity to sympathetic activation is correlated with resting BP, even within a normotensive range.


Assuntos
Força da Mão , Córtex Renal/irrigação sanguínea , Córtex Renal/metabolismo , Medula Renal/irrigação sanguínea , Medula Renal/metabolismo , Adulto , Velocidade do Fluxo Sanguíneo/fisiologia , Exercício Físico/fisiologia , Feminino , Voluntários Saudáveis , Humanos , Córtex Renal/inervação , Medula Renal/inervação , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Oxigênio/sangue , Artéria Renal/fisiologia , Circulação Renal/fisiologia , Sistema Nervoso Simpático/fisiologia , Adulto Jovem
2.
Nephron Physiol ; 120(3): p17-31, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22833057

RESUMO

BACKGROUND: Medullary blood flow is via vasa recta capillaries, which possess contractile pericytes. In vitro studies using isolated descending vasa recta show that pericytes can constrict/dilate descending vasa recta when vasoactive substances are present. We describe a live kidney slice model in which pericyte-mediated vasa recta constriction/dilation can be visualized in situ. METHODS: Confocal microscopy was used to image calcein, propidium iodide and Hoechst labelling in 'live' kidney slices, to determine tubular and vascular cell viability and morphology. DIC video-imaging of live kidney slices was employed to investigate pericyte-mediated real-time changes in vasa recta diameter. RESULTS: Pericytes were identified on vasa recta and their morphology and density were characterized in the medulla. Pericyte-mediated changes in vasa recta diameter (10-30%) were evoked in response to bath application of vasoactive agents (norepinephrine, endothelin-1, angiotensin-II and prostaglandin E(2)) or by manipulating endogenous vasoactive signalling pathways (using tyramine, L-NAME, a cyclo-oxygenase (COX-1) inhibitor indomethacin, and ATP release). CONCLUSIONS: The live kidney slice model is a valid complementary technique for investigating vasa recta function in situ and the role of pericytes as regulators of vasa recta diameter. This technique may also be useful in exploring the role of tubulovascular crosstalk in regulation of medullary blood flow.


Assuntos
Capilares/fisiologia , Medula Renal/irrigação sanguínea , Pericitos/fisiologia , Vasoconstrição/fisiologia , Trifosfato de Adenosina/metabolismo , Angiotensina II/metabolismo , Angiotensina II/farmacologia , Animais , Antígenos/metabolismo , Capilares/citologia , Sobrevivência Celular/fisiologia , Endotelina-1/metabolismo , Endotelina-1/farmacologia , Inibidores Enzimáticos/farmacologia , Imuno-Histoquímica , Técnicas In Vitro , Indometacina/farmacologia , Medula Renal/inervação , Medula Renal/metabolismo , Masculino , Microscopia Confocal , NG-Nitroarginina Metil Éster/farmacologia , Norepinefrina/metabolismo , Norepinefrina/farmacologia , Pericitos/citologia , Proteoglicanas/metabolismo , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Sistema Nervoso Simpático/fisiologia , Vasoconstrição/efeitos dos fármacos , Vasoconstritores/metabolismo , Vasoconstritores/farmacologia
3.
Clin Exp Pharmacol Physiol ; 37(2): e58-69, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19566838

RESUMO

1. Angiotensin (Ang) II has multiple actions in the renal medullary circulation. It can induce vasodilatation and blunt the response of medullary blood flow (MBF) to renal nerve activation through AT(1) receptor-mediated release of nitric oxide (NO) and/or vasodilator prostaglandins. These actions require high intravascular and/or intratubular AngII concentrations, so are not apparent under physiological conditions. 2. Nevertheless, these mechanisms blunt the responsiveness of MBF to AT(1) receptor-mediated vasoconstriction. When these protective mechanisms fail, as when oxidative stress reduces NO bioavailability in the medullary circulation, AngII reduces MBF. If sustained, reduced MBF leads to the development of hypertension. 3. Chronic activation of the renin-angiotensin system (RAS) induces oxidative stress in the kidney. Therefore, MBF may be reduced in models of hypertension associated with RAS activation both because AngII levels per se are increased and because of increased responsiveness of MBF to AngII-induced vasoconstriction. 4. Endogenous AngII enhances the responsiveness of MBF to renal nerve stimulation, whereas NO blunts it. Chronic RAS activation and/or oxidative stress should therefore be expected to enhance MBF responses to renal nerve stimulation. Consistent with this, reductions in MBF induced by renal nerve stimulation are enhanced in rabbits with AngII-induced hypertension, renovascular hypertension or after 9 weeks of fat feeding. 5. We conclude that the ability of endogenous AngII to reduce MBF and enhance the response of MBF to activation of the renal nerves could contribute to the development of hypertension under conditions of RAS activation, especially if accompanied by increased renal sympathetic nerve activity.


Assuntos
Angiotensina II/fisiologia , Hipertensão Renal/fisiopatologia , Medula Renal/irrigação sanguínea , Medula Renal/fisiologia , Circulação Renal/fisiologia , Animais , Cães , Medula Renal/inervação , Camundongos , Óxido Nítrico/fisiologia , Estresse Oxidativo/fisiologia , Prostaglandinas/fisiologia , Coelhos , Ratos , Circulação Renal/efeitos dos fármacos , Sistema Renina-Angiotensina/fisiologia , Sistema Nervoso Simpático/fisiologia , Vasoconstrição/efeitos dos fármacos , Vasoconstritores/farmacologia , Vasodilatadores/farmacologia
4.
Hypertension ; 52(5): 938-44, 2008 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18809793

RESUMO

The N-methyl-D-aspartate (NMDA) subtype of the ionotropic glutamate receptor is found in the periphery. The present study tested whether NMDA receptors (NMDARs) are present in the ends of afferent renal nerves in the renal pelvis, an area concerned mainly with transmitting sensation and the to reflex regulation of body fluid. The main NMDAR subunit, NMDAzeta1, was found to be more abundant in the renal pelvis than the renal cortex and medulla, and was mainly colocalized with the pan-neuronal marker PGP9.5 or the sensory nerve marker, the neurokinin-1 receptor. However, NMDAzeta1 mRNA was undetectable, suggesting that it might be synthesized outside the renal pelvis. Intrarenal arterial administration of the specific ion channel blocker (+)-MK-801, but not the inactive enantiomer (-)-MK-801, decreased urine output and sodium excretion. High doses of (+)-MK-801 also caused regional vasoconstriction in the renal cortex, as determined by laser-Doppler flowmetry. Intrapelvic administration of the NMDAR ligand D-serine caused a dose-dependent increase in substance P (SP) release and afferent renal nerve activity, but had no effect on arterial pressure. The D-serine-induced sensory activation and SP release were abrogated by (+)-MK-801, the SP receptor blocker L-703,606, or dorsal rhizotomy. Increasing intrapelvic pressure resulted in an increase in afferent renal nerve activity and a diuretic/natriuretic response. Interestingly, these effects were attenuated by prior administration of (+)-MK-801. These results indicate that NMDAR-positive sensory nerves are present in the renal pelvis and contribute to the renorenal reflex control of body fluid.


Assuntos
Rim/inervação , Mecanorreceptores/metabolismo , Neurônios Aferentes/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Animais , Maleato de Dizocilpina/farmacologia , Relação Dose-Resposta a Droga , Antagonistas de Aminoácidos Excitatórios/farmacologia , Feminino , Rim/metabolismo , Córtex Renal/inervação , Córtex Renal/metabolismo , Medula Renal/inervação , Medula Renal/metabolismo , Mecanorreceptores/efeitos dos fármacos , Quinuclidinas/farmacologia , Ratos , Ratos Wistar , Receptores de N-Metil-D-Aspartato/efeitos dos fármacos , Serina/farmacologia , Substância P/antagonistas & inibidores , Substância P/metabolismo
5.
Exp Lung Res ; 33(5): 259-75, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17620187

RESUMO

Increasing the extravascular fluid of the airways acutely by obstructing pulmonary lymph drainage causes a reflex diuresis mediated by neuronal nitric oxide synthase in the renal medulla. The authors examined this reflex in rabbits with a chronic increase in extravascular fluid of the airways resulting from surgically induced mitral regurgitation. Intact rabbits served as controls. Renal neuronal (nNOS) and endothelial (eNOS) nitric oxide synthase expressions were also examined. The reflex was absent in rabbits with mitral regurgitation. There were significant increases in medullary and cortical nNOS mRNA compared to controls. The observed changes in mRNA levels correlated with nNOS protein levels. eNOS mRNA was unaffected.


Assuntos
Obstrução das Vias Respiratórias/fisiopatologia , Diurese/fisiologia , Água Extravascular Pulmonar/fisiologia , Sistema Linfático/fisiopatologia , Insuficiência da Valva Mitral/fisiopatologia , Reflexo/fisiologia , Animais , Regulação Enzimológica da Expressão Gênica , Córtex Renal/irrigação sanguínea , Córtex Renal/enzimologia , Córtex Renal/inervação , Medula Renal/irrigação sanguínea , Medula Renal/enzimologia , Medula Renal/inervação , Valva Mitral/fisiopatologia , Óxido Nítrico Sintase Tipo I/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , RNA Mensageiro/metabolismo , Coelhos , Fluxo Sanguíneo Regional/fisiologia , Sistema Renina-Angiotensina/fisiologia
6.
Kidney Blood Press Res ; 30(3): 129-44, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17446713

RESUMO

BACKGROUND/METHODS: We have examined the hypothesis that cyst formation is key in the pathogenesis of cardiovascular disease in a Lewis polycystic kidney (LPK) model of autosomal-recessive polycystic kidney disease (ARPKD), by determining the relationship between cyst development and indices of renal function and cardiovascular disease. RESULTS: In the LPK (n = 35), cysts appear at week 3 (1.1 +/- 0.1 mm) increasing to week 24 (2.8 +/- 2 mm). Immunostaining for nephron-specific segments indicate cysts develop predominantly from the collecting duct. Cyst formation preceded hypertension (160 +/- 22 vs. Lewis control 105 +/- 20 mm Hg systolic blood pressure (BP), n = 12) at week 6, elevated creatinine (109 +/- 63 vs. 59 +/- 6 micromol/l, n = 16) and cardiac mass (0.7 vs. 0.4% bodyweight, n = 15) at week 12, and left ventricular hypertrophy (2,898 +/- 207 vs. 1,808 +/- 192 mum, n = 14) at week 24 (all p < or = 0.05). Plasma-renin activity and angiotensin II were reduced in 10- to 12-week LPK (2.2 +/- 2.9 vs. Lewis 11.9 +/- 4.9 ng/ml/h, and 25.0 +/- 19.1 vs. 94.9 +/- 64.4 pg/ml, respectively, n = 26, p < or = 0.05). Ganglionic blockade (hexamethonium 3.3 mg/kg) significantly reduced mean BP in the LPK (52 vs. Lewis 4%, n = 9, p < or = 0.05). CONCLUSION: Cyst formation is a key event in the genesis of hypertension while the sympathetic nervous system is important in the maintenance of hypertension in this model of ARPKD.


Assuntos
Modelos Animais de Doenças , Hipertensão Renal/patologia , Hipertrofia Ventricular Esquerda/patologia , Rim Policístico Autossômico Recessivo/patologia , Ratos Mutantes , Animais , Anticorpos Monoclonais , Biomarcadores/metabolismo , Creatinina/sangue , Feminino , Hipertensão Renal/etiologia , Hipertensão Renal/genética , Hipertrofia Ventricular Esquerda/etiologia , Hipertrofia Ventricular Esquerda/genética , Imuno-Histoquímica , Córtex Renal/inervação , Córtex Renal/metabolismo , Córtex Renal/patologia , Medula Renal/inervação , Medula Renal/metabolismo , Medula Renal/patologia , Túbulos Renais Distais/inervação , Túbulos Renais Distais/metabolismo , Túbulos Renais Distais/patologia , Túbulos Renais Proximais/inervação , Túbulos Renais Proximais/metabolismo , Túbulos Renais Proximais/patologia , Fígado/metabolismo , Fígado/patologia , Masculino , Miocárdio/metabolismo , Miocárdio/patologia , Rim Policístico Autossômico Recessivo/complicações , Rim Policístico Autossômico Recessivo/genética , Valor Preditivo dos Testes , Ratos , Ratos Endogâmicos Lew , Sistema Renina-Angiotensina/fisiologia , Sistema Nervoso Simpático/efeitos dos fármacos , Sistema Nervoso Simpático/fisiologia , Simpatolíticos/farmacologia , Fatores de Tempo , Ureia/sangue
7.
Exp Physiol ; 90(3): 341-7, 2005 May.
Artigo em Inglês | MEDLINE | ID: mdl-15653715

RESUMO

The role of adrenergic receptors in the reflex diuresis in response to pulmonary lymphatic drainage was examined in anaesthetized, artificially ventilated New Zealand White rabbits. Pulmonary lymphatic drainage was obstructed by raising the pressure in a pouch created from the right external jugular vein. This pulmonary lymphatic obstruction results in a reflex increase in urine flow and sodium excretion. This reflex is abolished by renal denervation and by administration of L-NAME, a non-selective inhibitor of nitric oxide synthase. Also, infusion of the relatively selective neuronal nitric oxide synthase blocker, 7-nitroindazole sodium salt, into the renal medulla abolished the reflex diuresis. In this study the effects of adrenergic receptor antagonists on the reflex increase in urine were observed. Both ureters were cannulated in order to determine urine flow from both kidneys separately. Prazosin, an alpha1 adrenergic receptor antagonist, was infused into the renal medulla of the right kidney, while the left kidney acted as control. Administration of prazosin in this manner did not block the reflex diuresis in response to pulmonary lymphatic obstruction in either kidney. However, rauwolscine, an alpha2 adrenergic receptor antagonist, abolished the reflex increase in urine and sodium excretion in the ipsilateral kidney while preserving it in the contralateral kidney. These findings suggest that the increase in urine flow in rabbits caused by pulmonary lymphatic obstruction is dependent upon activation of alpha2 adrenergic receptors within the renal medulla.


Assuntos
Diurese , Medula Renal/inervação , Medula Renal/fisiopatologia , Pneumopatias/fisiopatologia , Doenças Linfáticas/fisiopatologia , Receptores Adrenérgicos/metabolismo , Reflexo , Animais , Pneumopatias/complicações , Doenças Linfáticas/complicações , Modelos Biológicos , Coelhos
8.
Clin Exp Pharmacol Physiol ; 31(5-6): 387-96, 2004.
Artigo em Inglês | MEDLINE | ID: mdl-15191418

RESUMO

There is strong evidence that the renal medullary circulation plays a key role in long-term blood pressure control. This, and evidence implicating sympathetic overactivity in development of hypertension, provides the need for understanding how sympathetic nerves affect medullary blood flow (MBF). The precise vascular elements that regulate MBF under physiological conditions are unknown, but likely include the outer medullary portions of descending vasa recta and afferent and efferent arterioles of juxtamedullary glomeruli, all of which receive dense sympathetic innervation. Many early studies of the impact of sympathetic drive on MBF were flawed, both because of the methods used for measuring MBF and because single and often intense neural stimuli were tested. Recent studies have established that MBF is less sensitive than cortical blood flow (CBF) to electrical renal nerve stimulation, particularly at low stimulus intensities. Indeed, MBF appears to be refractory to increases in endogenous renal sympathetic nerve activity within the physiological range in all but the most extreme cases. Multiple mechanisms appear to operate in concert to blunt the impact of sympathetic drive on MBF, including counter-regulatory roles of nitric oxide and perhaps even paradoxical angiotensin II-induced vasodilatation. Regional differences in the geometry of glomerular arterioles are also likely to predispose MBF to be less sensitive than CBF to any given vasoconstrictor stimulus. Failure of these mechanisms would promote reductions in MBF in response to physiological activation of the renal nerves, which could, in turn, lead to salt and water retention and hypertension.


Assuntos
Medula Renal/irrigação sanguínea , Medula Renal/inervação , Neurônios/fisiologia , Circulação Renal/fisiologia , Animais , Pressão Sanguínea/fisiologia , Humanos , Medula Renal/fisiologia , Perfusão
9.
Kidney Int ; 65(3): 982-9, 2004 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-14871418

RESUMO

BACKGROUND: As yet, there are only limited data available on the exact role of endothelin (ET) acting through endothelin-A (ETA) receptors in renal sodium and water regulation and the potential functional implications of an interaction of the renal ET system with renal nerves in normotensive and spontaneously hypertensive rats. METHODS: Experiments were carried out in 64 male conscious spontaneously hypertensive rats and in 56 normotensive Wistar-Kyoto (WKY) rats. Bilateral renal denervation (BRD) was performed in 32 spontaneously hypertensive rats and 28 WKY rats 7 days before the experiments. The ETA receptor antagonist, BQ-123 (16.4 nmol/kg x min intravenously) or the endothelin-B (ETB) receptor antagonist, BQ-788 (25 nmol/kg x min intravenously) were infused at a rate of 25 microL/min for 50 minutes. RESULTS: Renal papillary ET-1 concentration in intact spontaneously hypertensive rats was 67.8% lower than in intact WKY rats (154 +/- 40 fmol/mg protein vs. 478 +/- 62 fmol/mg protein, P < 0.01). BRD decreased papillary ET-1 by 73.5% in WKY rats to 127 +/- 19 fmol/mg protein (P < 0.001), but had no effect in spontaneously hypertensive rats (122 +/- 37 fmol/mg protein). BRD, BQ-123, or BQ-788 did not affect glomerular filtration rate (GFR) or renal blood flow (RBF) in any of the groups. In intact WKY, BQ-123 decreased urine flow rate (V) from 4.65 +/- 0.44 microL/min.100 g body weight to 2.44 +/- 0.35 microL/min.100 g body weight (P < 0.01), urinary excretion of sodium (UNaV) from 238.2 +/- 27.4 to 100.2 +/- 17.0 (P < 0.01) and potassium (UKV) from 532.1 +/- 62.6 nmol/min.100 g body weight to 243.0 +/- 34.2 nmol/min.100 g body weight (P < 0.001), whereas BQ-788 decreased only V and UNaV. In renal denervated WKY, BQ-123 or BQ-788 did not alter V, UNaV, or UKV. In intact spontaneously hypertensive rats BQ-123 but not BQ-788 decreased V from 3.94 +/- 0.48 microL/min.100 g body weight to 2.55 +/- 0.44 microL/min.100 g body weight (P < 0.05). In renal denervated spontaneously hypertensive rats neither BQ-123 nor BQ-788 affected V, UNaV, or UKV. CONCLUSION: An interaction between ET and renal nerves is involved in the control of renal function. Moreover, renal nerves participate in the regulation of ET-1 production within the kidney. Finally, decreased synthesis of ET-1 in the renal papilla of spontaneously hypertensive rats may contribute to development and/or maintenance of hypertension due to modulation of renal excretory function.


Assuntos
Antagonistas do Receptor de Endotelina A , Hipertensão Renal/metabolismo , Córtex Renal/inervação , Medula Renal/inervação , Receptor de Endotelina A/metabolismo , Animais , Anti-Hipertensivos/farmacologia , Pressão Sanguínea , Denervação , Endotelina-1/sangue , Hipertensão Renal/tratamento farmacológico , Córtex Renal/efeitos dos fármacos , Córtex Renal/metabolismo , Medula Renal/efeitos dos fármacos , Medula Renal/metabolismo , Masculino , Natriurese/efeitos dos fármacos , Oligopeptídeos/farmacologia , Peptídeos Cíclicos/farmacologia , Piperidinas/farmacologia , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Urina
10.
Am J Physiol Regul Integr Comp Physiol ; 280(1): R62-8, 2001 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-11124135

RESUMO

The role of renal sympathetic nerve activity (RSNA) in the physiological regulation of medullary blood flow (MBF) remains ill defined, yet regulation of MBF may be crucial to long-term arterial pressure regulation. To investigate the effects of reflex increases in RSNA on intrarenal blood flow distribution, we exposed pentobarbital sodium-anesthetized, artificially ventilated rabbits (n = 7) to progressive hypoxia while recording RSNA, cortical blood flow (CBF), and MBF using laser-Doppler flowmetry. Another group of animals with denervated kidneys (n = 6) underwent the same protocol. Progressive hypoxia (from room air to 16, 14, 12, and 10% inspired O(2)) significantly reduced arterial oxygen partial pressure (from 99 +/- 3 to 65 +/- 2, 51 +/- 2, 41 +/- 1, and 39 +/- 2 mmHg, respectively) and significantly increased RSNA (by 8 +/- 3, 44 +/- 25, 62 +/- 21, and 76 +/- 37%, respectively, compared with room air) without affecting mean arterial pressure. There were significant reductions in CBF (by 2 +/- 1, 5 +/- 2, 11 +/- 3, and 14 +/- 2%, respectively) in intact but not denervated rabbits. MBF was unaffected by hypoxia in either group. Thus moderate reflex increases in RSNA cause renal cortical vasoconstriction, but not at vascular sites regulating MBF.


Assuntos
Córtex Renal/fisiologia , Medula Renal/fisiologia , Reflexo/fisiologia , Circulação Renal/fisiologia , Sistema Nervoso Simpático/fisiologia , Anestesia , Animais , Pressão Sanguínea , Taxa de Filtração Glomerular/fisiologia , Frequência Cardíaca , Hipóxia/fisiopatologia , Córtex Renal/irrigação sanguínea , Córtex Renal/inervação , Medula Renal/irrigação sanguínea , Medula Renal/inervação , Oxigênio/sangue , Coelhos , Sódio/urina , Simpatectomia , Urina , Vasoconstrição/fisiologia
11.
Am J Physiol Regul Integr Comp Physiol ; 279(3): R907-16, 2000 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-10956248

RESUMO

To test whether renal sympathetic nerve activity (RSNA) can differentially regulate blood flow in the renal medulla (MBF) and cortex (CBF) of pentobarbital sodium-anesthetized rabbits, we electrically stimulated the renal nerves while recording total renal blood flow (RBF), CBF, and MBF. Three stimulation sequences were applied 1) varying amplitude (0.5-8 V), 2) varying frequency (0.5-8 Hz), and 3) a modulated sinusoidal pattern of varying frequency (0. 04-0.72 Hz). Increasing amplitude or frequency of stimulation progressively decreased all flow variables. RBF and CBF responded similarly, but MBF responded less. For example, 0.5-V stimulation decreased CBF by 20 +/- 9%, but MBF fell by only 4 +/- 6%. The amplitude of oscillations in all flow variables was progressively reduced as the frequency of sinusoidal stimulation was increased. An increased amplitude of oscillation was observed at 0.12 and 0.32 Hz in MBF and to a lesser extent RBF, but not CBF. MBF therefore appears to be less sensitive than CBF to the magnitude of RSNA, but it is more able to respond to these higher frequencies of neural stimulation.


Assuntos
Córtex Renal/irrigação sanguínea , Córtex Renal/inervação , Medula Renal/irrigação sanguínea , Medula Renal/inervação , Sistema Nervoso Simpático/fisiologia , Anestesia , Animais , Pressão Sanguínea/fisiologia , Estimulação Elétrica , Frequência Cardíaca/fisiologia , Fluxometria por Laser-Doppler , Coelhos , Circulação Renal/fisiologia
12.
Brain Res ; 834(1-2): 196-9, 1999 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-10407115

RESUMO

Sympathetic activity was recorded from the renal nerve and the ventral tail artery of anesthetized rats while neurons in three sympathetic premotor groups, the rostroventrolateral medulla (RVLM), rostroventromedial medulla (RVMM) and medullary raphe, were activated by microinjections of sodium glutamate (1-15 nl, 50 mM). RVLM activation increased renal nerve activity by 27+/-3% but caused small, inconsistent effects on the tail outflow (+15+/-10%). Raphe neuron stimulation had little effect on the renal nerve (+8+/-3%), but strongly increased tail sympathetic unit activity (+125+/-28%). RVMM neurons had little effect on either outflow. These results indicate that different premotor cell groups have different sympathetic actions.


Assuntos
Medula Renal/inervação , Bulbo/fisiologia , Neurônios Motores/fisiologia , Células-Tronco/fisiologia , Sistema Nervoso Simpático/fisiologia , Cauda/irrigação sanguínea , Animais , Artérias/inervação , Masculino , Bulbo/citologia , Núcleos da Rafe/citologia , Núcleos da Rafe/fisiologia , Ratos , Ratos Sprague-Dawley , Estimulação Química
13.
J Am Soc Nephrol ; 10(4): 704-13, 1999 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-10203353

RESUMO

Chronic renal failure is associated with disturbances in nitric oxide (NO) production. This study was conducted to determine the effect of 5/6 nephrectomy (5/6 Nx) on expression of intrarenal neuronal nitric oxide synthase (nNOS) in the rat. In normal rat kidney, nNOS protein was detected in the macula densa and in the cytoplasm and nuclei of cells of the inner medullary collecting duct by both immunofluorescence and electron microscopy. Western blot analysis revealed that 2 wk after 5/6 Nx, there were significant decreases in nNOS protein expression in renal cortex (sham: 95.42+/-15.60 versus 5/6 Nx: 47.55+/-12.78 arbitrary units, P<0.05, n = 4) and inner medulla (sham: 147.70+/-26.96 versus 5/6 Nx: 36.95+/-17.24 arbitrary units, P<0.005, n = 8). Losartan treatment was used to determine the role of angiotensin II (AngII) AT1 receptors in the inhibition of nNOS expression in 5/6 Nx. Losartan had no effect on the decreased expression of nNOS in the inner medulla, but partially increased nNOS protein expression in the cortex of 5/6 Nx rats. In contrast, in sham rats losartan significantly inhibited nNOS protein expression in the cortex (0.66+/-0.04-fold of sham values, P<0.05, n = 6) and inner medulla (0.74+/-0.12-fold of sham values, P<0.05, n = 6). nNOS mRNA was significantly decreased in cortex and inner medulla from 5/6 Nx rats, and the effects of losartan on nNOS mRNA paralleled those observed on nNOS protein expression. These data indicate that 5/6 Nx downregulates intrarenal nNOS mRNA and protein expression. In normal rats, AngII AT1 receptors exert a tonic stimulatory effect on expression of intrarenal nNOS. These findings suggest that the reduction in intrarenal nNOS expression in 5/6 Nx may play a role in contributing to hypertension and altered tubular transport responses in chronic renal failure.


Assuntos
Córtex Renal/inervação , Medula Renal/inervação , Neurônios/enzimologia , Óxido Nítrico Sintase/metabolismo , RNA Mensageiro/análise , Análise de Variância , Antagonistas de Receptores de Angiotensina , Animais , Western Blotting , Núcleo Celular/ultraestrutura , Técnicas de Cultura , Citoplasma/ultraestrutura , Modelos Animais de Doenças , Regulação para Baixo/fisiologia , Imunofluorescência , Córtex Renal/patologia , Medula Renal/patologia , Losartan/farmacologia , Masculino , Nefrectomia , Óxido Nítrico Sintase/análise , Óxido Nítrico Sintase/genética , Reação em Cadeia da Polimerase , RNA Mensageiro/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Receptor Tipo 1 de Angiotensina , Receptor Tipo 2 de Angiotensina , Sensibilidade e Especificidade
14.
J Hypertens ; 15(9): 1041-8, 1997 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-9321753

RESUMO

BACKGROUND: Hypertension features an exaggerated natriuresis after acute volume expansion. In humans, the degree of exaggerated natriuresis appears to be correlated inversely to the level of angiotensin (Ang) II. OBJECTIVE: To test the hypothesis that the degree of exaggerated natruresis is correlated to the level of Ang II by studying two rat models, transgenic rats (TGR) with and extra renin gene (TGR mRen2)27 and desoxycorticosterone acetate (DOCA)-salt rats, in comparison with Sprague-Dawley Hannover (SDH) rat controls. METHODS: All of the rats were uninephrectomized for 1 month. DOCA-salt rats were implanted with a DOCA pallet and drank 1% saline. Rats were anesthetized and their left kidneys were instrumented with renal sympathetic nerve activity (RSNA) electrodes and laser-Doppler cortical and medullary flow probes. The glomerular filtration rate, diuresis, and natriuresis were measured for 120 min after sodium loading (5% body weight 0.9% saline administered during 3 min). Kidneys were examined histologically. RESULTS: The blood pressure in TGR and DOCA-salt rats was 40-50 mmHg higher than that in SDH rats, and decreased briefly after volume expansion for all groups. The diuresis and natriuresis of TGR and DOCA-salt rats were greater than those of SDH rats. The medullary blood flow increased and the cortical blood flow in SDH decreased, whereas the cortical blood flow in TGR and DOCA-salt rats remained high. The RSNA in rats of all groups decreased; however, this decrease was greater in SDH than it was in TGR and DOCA-salt rats. The histology was affected most severely for the DOCA-salt rats. CONCLUSIONS: Exaggerated natriuresis occurred in hypertensive rats regardless of their Ang II status. Both strains were characterized by a smaller decrease in RSNA and a preserved cortical blood flow in the face of volume expansion. These data do not support the notion that exaggerated natriuresis is a function of renin-level suppression for rats.


Assuntos
Angiotensina II/fisiologia , Hipertensão/fisiopatologia , Natriurese , Renina/fisiologia , Animais , Animais Geneticamente Modificados , Pressão Sanguínea/efeitos dos fármacos , Córtex Renal/irrigação sanguínea , Córtex Renal/inervação , Córtex Renal/patologia , Testes de Função Renal , Medula Renal/irrigação sanguínea , Medula Renal/inervação , Medula Renal/patologia , Fluxometria por Laser-Doppler , Masculino , Natriurese/efeitos dos fármacos , Ratos , Ratos Endogâmicos , Circulação Renal/efeitos dos fármacos , Renina/genética , Sódio/farmacologia , Sistema Nervoso Simpático/efeitos dos fármacos
15.
J Auton Nerv Syst ; 45(2): 125-38, 1993 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-7904276

RESUMO

Indirect immunohistochemical methods were used to visualize nerves immunoreactive for tyrosine hydroxylase (TH), dopamine beta hydroxylase (DBH), neuropeptide Y, (NPY) and calcitonin gene-related peptide (CGRP) in sections of the kidneys of cats of different ages. Nerve terminals immunoreactive for TH, DBH and NPY innervated interlobar veins and the renal arterial tree including medullary vascular bundles of cats of each age studied. Most nerve terminals immunoreactive for CGRP innervated interlobar arteries. In kidneys of cats 2 to 10 weeks old, TH- and DBH-immunoreactive axons formed elaborate plexuses that were distributed throughout much of the outer two thirds of the inner medulla. Inner medullary NPY-immunoreactive nerve terminals formed sparse plexuses by comparison, thus suggesting a large population of TH-immunoreactive nerve terminals not immunoreactive for NPY. Plexuses immunoreactive for CGRP also innervated the inner medullae of young cats. Some inner medullary axons appeared degenerate in 8 and 10 week old cats, and no inner medullary nerve terminal plexuses were visualized in 12 week old or adult cats. Cell death or paring of axons resulting from mechanisms intrinsic to the neuronal population or from a change in trophic factors secreted or expressed by cells in the medulla may effect the loss of inner medullary nerve terminals in the kidneys of young cats.


Assuntos
Rim/inervação , Norepinefrina/fisiologia , Peptídeos/fisiologia , Envelhecimento/fisiologia , Animais , Peptídeo Relacionado com Gene de Calcitonina/imunologia , Peptídeo Relacionado com Gene de Calcitonina/metabolismo , Gatos , Morte Celular/fisiologia , Dopamina beta-Hidroxilase/imunologia , Dopamina beta-Hidroxilase/metabolismo , Feminino , Imuno-Histoquímica , Rim/enzimologia , Rim/crescimento & desenvolvimento , Medula Renal/inervação , Masculino , Fibras Nervosas/enzimologia , Neuropeptídeo Y/imunologia , Neuropeptídeo Y/metabolismo , Tirosina 3-Mono-Oxigenase/imunologia , Tirosina 3-Mono-Oxigenase/metabolismo
16.
Clin Exp Pharmacol Physiol ; 20(5): 351-4, 1993 May.
Artigo em Inglês | MEDLINE | ID: mdl-8100748

RESUMO

1. The effects of local infusion of angiotensin II (AII) into the rostral ventrolateral medulla (RVLM) pressor area on the renal sympathetic baroreflex were compared with the excitatory amino acid glutamate in urethane anaesthetized rabbits with chronically implanted renal nerve electrodes. Baroreflex blood pressure-renal nerve activity curves were obtained by intravenous infusion of phenylephrine and nitroprusside before and after treatments. 2. Infusion of 4 pmol/min of AII into the RVLM increased blood pressure by 12 +/- 2 mmHg and transiently increased resting sympathetic nerve activity. The renal sympathetic baroreflex curves were shifted to the right. The upper plateau of the sympathetic reflex increased by 29 +/- 8% (n = 6, P < 0.025). 3. Infusions of glutamate into the RVLM, at a dose which was equipressor to that of AII, also increased resting renal sympathetic nerve activity. In contrast to AII, this increase was maintained throughout the infusion. Glutamate shifted the reflex curve to the right and increased the upper plateau of the sympathetic reflex by 44 +/- 5% without affecting the lower plateau. 4. These results support the suggestion that AII can act at the level of the RVLM pressor area to facilitate baroreflex control of renal sympathetic activity in a similar fashion to that produced by fourth ventricular administration. 5. Thus the RVLM is a likely candidate site for modulation of the renal sympathetic baroreflex. The similarity of the actions of AII to those of glutamate suggest that it may directly excite sympathetic vasomotor cells in this region.


Assuntos
Angiotensina II/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Medula Renal/efeitos dos fármacos , Pressorreceptores/efeitos dos fármacos , Angiotensina II/administração & dosagem , Animais , Feminino , Glutamatos/farmacologia , Ácido Glutâmico , Medula Renal/inervação , Masculino , Microeletrodos , Pressorreceptores/fisiologia , Coelhos
18.
J Auton Nerv Syst ; 38(2): 97-104, 1992 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-1619214

RESUMO

Renal concentrations of the catecholamine neurotransmitters norepinephrine (NE) and dopamine (DA) in 19 cats were measured by reverse-phase high pressure liquid chromatography (HPLC) with electrochemical detection. Animals of five different age groups (2-4, 6-8, 10-12 and 16-20 weeks and adult animals one year and older) were anesthetized and the kidneys were excised, sectioned into cortical, outer medullary and inner medullary segments, and processed for HPLC. There were no statistical differences in cortical NE concentrations between the 2-4 week and adult age groups, suggesting that peak noradrenergic nerve terminal density in the cortex is achieved at or before 2-4 weeks of age. NE concentration in the outer medulla and DA concentration in the cortex and outer medulla increased from the 2-4 to the 10-12 week age group but did not change significantly in the older animals. There were significant decreases in inner medullary NE and DA concentrations from the 10-12-week to the 16-20 week age group. The decrease in concentration of inner medullary catecholamines in the early postnatal period is consistent with the reported total loss of tyrosine hydroxylase- and dopamine beta hydroxylase-immunoreactive inner medullary nerve terminals at approximately 12 weeks of age.


Assuntos
Envelhecimento/metabolismo , Catecolaminas/metabolismo , Rim/metabolismo , Animais , Gatos , Cromatografia Líquida de Alta Pressão , Eletroquímica , Feminino , Córtex Renal/efeitos dos fármacos , Córtex Renal/metabolismo , Medula Renal/inervação , Medula Renal/metabolismo , Masculino
19.
Am J Physiol ; 261(3 Pt 2): R727-37, 1991 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-1887961

RESUMO

In the present study, we sought to define the extent and source of tonic descending modulation of spinal neurons receiving visceral input from the afferent renal nerve (ARN). Spinal gray neurons responding to stimulation of the ARN in 64 chloralose-anesthetized rats were located primarily in laminae IV and V (70%), with fewer neurons located in laminae I and VII. ARN stimulation excited 76 and inhibited 8 neurons. Analysis of response latencies demonstrated that responses were due to activation of A delta- and/or C-fiber afferents. Reversible spinalization with cervical cold block (2-5 degrees C) affected activity in most neurons excited by ARN stimulation without affecting inhibited neurons. Cervical cold block increased the spontaneous activity of (disinhibited) the majority of neurons (54 of 76 neurons) and disfacilitated the spontaneous activity of 14 neurons. The evoked response to ARN stimulation was disinhibited by cold block in 51% and disfacilitated in 17% of the neurons, and there was a good correlation between neurons with disinhibited spontaneous activity and those with disinhibited evoked activity. Microinjections of muscimol (0.5-1 nmol) into the rostral medial medulla affected spontaneous and ARN-evoked activities similarly to cold block in 14 of 15 neurons, although the responses to muscimol were usually smaller in magnitude. We conclude that ARN input is modulated supraspinally and that the nucleus raphe magnus and adjacent neuropil contain neurons that contribute to tonic supraspinal inhibition of renal input in the rat.


Assuntos
Vias Aferentes/fisiologia , Medula Renal/inervação , Bulbo/fisiologia , Neurônios/fisiologia , Medula Espinal/fisiologia , Animais , Estimulação Elétrica , Potenciais Evocados , Masculino , Bulbo/efeitos dos fármacos , Potenciais da Membrana , Muscimol/farmacologia , Fibras Nervosas/fisiologia , Neurônios/efeitos dos fármacos , Ratos , Ratos Endogâmicos
20.
Neurosci Lett ; 114(2): 173-7, 1990 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-1975658

RESUMO

An indirect immunohistochemical method was used to visualize nerves immunoreactive for tyrosine hydroxylase (THI) and dopamine-beta-hydroxylase (DBHI) in kidney sections of cats 6 weeks and 2 and 3 months of age. THI and DBHI nerve terminals innervate the renal pelvis, interlobar veins and arterial tree including medullary vascular bundles of cats of each age studied. In kidneys of 6-week-old cats, THI and DBHI axons form elaborate plexuses that are distributed throughout much of the inner medulla, whereas some medullary axons appear to degenerate at 2 months and no inner medullary plexuses were visualized in 3-month-old cats. Transitory inner medullary nerves in the cat kidney may influence cellular development and play a role in salt and water balance.


Assuntos
Medula Renal/inervação , Terminações Nervosas/crescimento & desenvolvimento , Sistema Nervoso Simpático/crescimento & desenvolvimento , Envelhecimento , Animais , Axônios/enzimologia , Axônios/ultraestrutura , Gatos , Dopamina beta-Hidroxilase/análise , Feminino , Medula Renal/anatomia & histologia , Medula Renal/crescimento & desenvolvimento , Masculino , Terminações Nervosas/enzimologia , Sistema Nervoso Simpático/anatomia & histologia , Sistema Nervoso Simpático/enzimologia , Tirosina 3-Mono-Oxigenase/análise
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