Péptidos natriuréticos en la detección de disfunción ventricular izquierda en población de alto riesgo. Metaanálisis de pruebas diagnósticas / Natriuretic peptides in the detection of left ventricular dysfunction in a high risk population. A meta-analysis of diagnostic tests

Resumen Introducción: Las concentraciones de los péptidos natriuréticos en el plasma se han propuesto como un método de tamización para disfunción ventricular temprana. Objetivo: Comparar las características operativas del péptido natriurético tipo B (BNP) y de la fracción N-terminal (NT-proBNP) en población con factores de riesgo. Método: Metaanálisis de pruebas diagnósticas. Resultados: Se aplicó una estrategia de búsqueda mediante la cual se encontraron 86 referencias, de las cuales se seleccionaron 12 por criterios de inclusión. En 8 de estos estudios se evaluó el desempeño del BNP, en 3 el NT-proBNP y en uno ambas pruebas. Los puntos de corte para el BNP oscilaron entre 8 y 169,5 pg/ml, con una sensibilidad agrupada de 82,1% (IC 95%, 76,7-86,4%), una especificidad agrupada de 69% (IC 95%, 61,5-75,6%), un LR+ 2,65 (IC 95%, 2,17-3,23) y un LR( 0,26 (IC 95%, 0,21-0,32). Cuando solo se analizaron los datos para puntos de corte por debajo de 50 pg/ml la sensibilidad agrupada mejoró a 89,2% (IC 95%, 82,6-94%) y el LR( fue 0,23 (IC 95%, 0,14-0,40). Solo se analizaron 3 estudios sobre NT-proBNP, con puntos de corte entre 125 y 902 pg/ml, con sensibilidad agrupada del 97,2% (IC 95%, 90,2-99,7%), especificidad agrupada del 76,9% (IC 95%, 74,5-79,1%), LR+ 3,39 (IC 95%, 1,67-6,85) y LR( 0,07 (IC 95%, 0,02-0,23). Conclusión: El BNP y el NT-proBNP pueden ser útiles para descartar disfunción ventricular izquierda asintomática en pacientes en riesgo.

Abstract Introduction: The concentration of natriuretic peptides in plasma has been proposed as a screening method for early ventricular dysfunction. Objective: To compare the operative characteristics of B-type natriuretic peptide (BNP) and N-terminal pro b-type natriuretic peptide (NT-proBNP) fraction in a population with risk factors. Method: A meta-analysis of diagnostic tests. Results: A search strategy was applied that found 86 references, of which 12 were selected according to the inclusion criteria. The role of BNP was evaluated in 8 of these studies, that of NT-proBNP in 3, and both tests in one of them. The cut-off points for BNP varied between 8 and 169.5 pg/mL, with a grouped sensitivity of 82.1% (95% CI; 76.7-86.4%), a grouped specificity of 69% (95%CI; 61.5-75.6%), a positive likelihood ratio (LR+) of 2.65 (95% CI; 2.17-3.23) and a negative likelihood ratio (LR() of 0.26 (95% CI; 0.21-0.32). When the data were only analysed for cut-off points below 50 pg/mL, the grouped sensitivity improved to 89.2% (95% CI; 82.6-94%), and the LR( was 0.23 (95% CI; 0.14-0.40). Only 3 studies on NT-proBNP were analysed, with cut-off points between 125 and 902 pg/mL, a grouped specificity of 97.2% (95% CI; 90.2-99.7%), a grouped sensitivity of 76.9% (95% CI; 74.5-79.1%), LR+ 3.39 (95% CI; 1.67-6.85), and LR( 0.07 (95% CI; 0.02-0.23). Conclusion: BNP and NT-proBNP can be useful in ruling out asymptomatic left ventricular dysfunction in patients at risk.

Semiología y diagnóstico diferencial de la insuficiencia cardíaca crónica / Semiology and differential diagnosis of chronic heart failure

Resumen: la insuficiencia cardiaca es un síndrome clínico de etiología multifactorial de alta prevalencia en la población mundial y latinoamericana debido al aumento en la expectativa de vida. Actualmente el diagnóstico de este se basa en los hallazgos de pruebas diagnósticas como el ecocardiograma o pépticos natriuréticos, pero es importante para el personal médico conocer e identificar de manera clara los signos y síntomas que presentan los pacientes con insuficiencia cardiaca, pues es una tendencia actual el desconocer datos semiológicos importantes que fueron descritos y refinados durante los siglos XIX y XX, y que ahora son validados por la medicina basada en la evidencia. Lo anterior cobra importancia pues el papel que debe tener la creciente tecnología no es acabar o desplazar el conocimiento clínico, si no ser una herramienta complementaria para el buen cuidado del paciente y así llegar al mejor desenlace posible. Este artículo pretende brindar datos basados en la evidencia para hacer de la clínica la parte fundamental del proceso diagnóstico y de la relación médico paciente. También intenta ser una guía útil para estudiantes de medicina o médicos que se desenvuelven en sitios con pocos recursos económicos, ya que la elección adecuada de un examen diagnóstico solo puede ser llevada a cabo mediante un buen interrogatorio y examen físico.

Abstract: heart failure is a clinical syndrome with multifactorial etiology of high prevalence in the world and Latin American population due to the increase in life expectancy. Currently the diagnosis of this is based on the findings of diagnostic tests such as echocardiogram or natriuretic peptic, but it is important for the medical staff to know and clearly identify the signs and symptoms that patients with heart failure present, as it is a current trend To ignore important semiological data that were described and refined during the nineteenth and twentieth centuries, and which are now validated by evidence-based medicine. This is important because the role of growing technology is not to end or displace clinical knowledge, if not to be a complementary tool for good patient care and thus reach the best possible outcome. This article aims to provide data based on the evidence to make the clinic the fundamental part of the diagnostic process and the patient medical relationship. It is also intended to be a useful guide for medical students or physicians operating in poorly funded areas, as the proper choice of a diagnostic examination can only be carried out through a thorough examination and physical examination.

Changes in cardiac aldosterone and its synthase in rats with chronic heart failure: an intervention study of long-term treatment with recombinant human brain natriuretic peptide

The physiological mechanisms involved in isoproterenol (ISO)-induced chronic heart failure (CHF) are not fully understood. In this study, we investigated local changes in cardiac aldosterone and its synthase in rats with ISO-induced CHF, and evaluated the effects of treatment with recombinant human brain natriuretic peptide (rhBNP). Sprague-Dawley rats were divided into 4 different groups. Fifty rats received subcutaneous ISO injections to induce CHF and the control group (n=10) received equal volumes of saline. After establishing the rat model, 9 CHF rats received no further treatment, rats in the low-dose group (n=8) received 22.5 μg/kg rhBNP and those in the high-dose group (n=8) received 45 μg/kg rhBNP daily for 1 month. Cardiac function was assessed by echocardiographic and hemodynamic analysis. Collagen volume fraction (CVF) was determined. Plasma and myocardial aldosterone concentrations were determined using radioimmunoassay. Myocardial aldosterone synthase (CYP11B2) was detected by quantitative real-time PCR. Cardiac function was significantly lower in the CHF group than in the control group (P<0.01), whereas CVF, plasma and myocardial aldosterone, and CYP11B2 transcription were significantly higher than in the control group (P<0.05). Low and high doses of rhBNP significantly improved hemodynamics (P<0.01) and cardiac function (P<0.05) and reduced CVF, plasma and myocardial aldosterone, and CYP11B2 transcription (P<0.05). There were no significant differences between the rhBNP dose groups (P>0.05). Elevated cardiac aldosterone and upregulation of aldosterone synthase expression were detected in rats with ISO-induced CHF. Administration of rhBNP improved hemodynamics and ventricular remodeling and reduced myocardial fibrosis, possibly by downregulating CYP11B2 transcription and reducing myocardial aldosterone synthesis.

Diuretic activity of Boswellia serrata Roxb. oleo gum extract in albino rats

The aim of the study was to evaluate the effect of crude aqueous extract of Boswellia serrata Roxb. oleo gum on urinary electrolytes, pH and diuretic activity in normal albino rats. Moreover, acute toxicity of the gum extract was assessed using mice. Albino rats were divided into five groups. Control group received normal saline [10 mg/kg], reference group received furosemide [10 mg/kg] and test groups were given different doses of crude extract [10, 30 and 50 mg/kg] by intra-peritoneal route, respectively. The Graph Pad Prism was used for the statistical analysis and p < 0.05 was considered statistically significant. Significant diuretic, kaliuretic and natriuretic effects were observed in the treated groups in a dose dependent manner. Diuretic index showed good diuretic activity of the crude extract. Lipschitz values indicated that the crude extract, at the dose of 50 mg/kg, showed 44% diuretic activity compared to the reference drug. No lethal effects were observed among albino mice even at the higher dose of 3000 mg/kg. It is concluded that aqueous extract of Boswellia serrata oleo gum, at the dose of 50 mg/kg showed significant effects on urinary volume and concentration of urinary electrolytes with no signs of toxicity

Aminoterminal proBrain Natriuretic Peptide en sangre como marcador de isquemia miocárdica en la evaluación de pacientes con dolor torácico y probabilidad intermedia para síndrome coronario agudo / Natriuretic peptide amino proBrain blood as a marker of myocardial ischemia in the evaluation of patients with chest pain and intermediate risk for acute coronary syndrome

Introducción: lo péptidos natruréticos son una familia de hormonas polipeptídicas sistetizadas, acumuladas en gránulos de reserva y secretadas por los cardiocitos auriculares y ventriculares; ellas regulan el tono vascular y mecanismos renales y metabólicos. Aminoterminal proBrain Natriuretic Peptide (NT.proBNP), es un fragmento inactivo que resulta del clivaje del proBrain Natriuretic Peptide y es un biomarcador de disfunción cardíaca. Los niveles plasmáticos de los péptidos natriuréticos pueden elevarse ante estímulos diversos como insuficiencia cardíaca, isquemia o inflamción. En los síndromes coronarios agudos son marcadores de riesgo y permiten una adecuada estratificación. Hipótesis: los niveles plasmáticos de NT-proBNP medidos antes de una prueba de esfuerzo en pacientes con probabilidad intermedia de síndrome coronario agudo, e inmediatamente después de maximo esfuerzo, detectarán isquemia miocárdica y predecirán eventos cardiovasculares a 30 días y 6 meses.

Introduction: natriuretic peptides are a family of polypeptide hormones synthesized, stored and secreted by atrial and ventricular cardiocytes; they regulate the vascular tone, and renal and metabolic mechanisms. Aminoterminal proBrain Natriuretic Peptide (NT-proBNP) is an inactive fragment thas is cleaved from the proBrain Natriuretic Peptide and it is a biomarker of different stimuli sch as heart failure, ischemia or inflammation. In acute coronary syndromes they are risk markers enabling adequate risk stratification. Hypothesis: plasma levels of NT-proBNP measured before a stress test in patients with an intermediate probability of acute coronary syndrome, and immediately after maximum stress will detect myocardial ischemia and will predict cardiovascular events at 30 days and 6 months.

Peptídeo natriurético na emergência: quando usar? / Natriuretic peptide in the emergency setting: when to use?

JUSTIFICATIVA E OBJETIVOS: O diagnóstico de dispneiana sala de emergência, muitas vezes é desafiador devido à ampla possibilidade de diagnósticos diferenciais. A utilização de um biomarcador como o peptídeo natriurético (PN) pode auxiliar na elucidação diagnóstica, assim como determinar o prognóstico destes pacientes. O objetivo deste estudo foi rever as principais indicações e situações clinicas que o PN pode auxiliar o emergencista. CONTEÚDO: Estudos publicados entre 1990 e 2008 foram selecionados no banco de dados da Medline através das palavras-chave peptídeo natriurético cerebral, emergência, diagnóstico, prognóstico e tratamento, assim como diretrizes internacionais foram buscados no link http://sumsearch.uthscsa.edu. Adicionalmente, referências destes artigos, capítulos de livros e artigos históricos foram avaliados. O Médica peptídeo natriurético cerebral (BNP) é uma molécula sintetizadanas células cardíacas produzindo o peptídeo hormonalativo e seu fragmento biologicamente inativo, o N-terminal-pró-BNP. Sua ativação geralmente ocorre em resposta à sobrecarga volumétrica, pressórica e/ou aumento da tensão de parede ventricular. A liberação deste neuro-hormônio equilibra os efeitos do sistema renina-angiotensina-aldosterona (RAAS), endotelina e ativação simpática; ocasionando vasodilatação e natriurese. CONCLUSÃO: Sua utilização adequada é uma importante ferramenta diagnóstica na sala de emergência, servindo também como elemento prognóstico e de avaliação terapêutica em situações clínicas críticas, tais como insuficiência cardíaca descompensada e embolia pulmonar. Sua praticidade à beira do leito pode auxiliar e até direcionar o tratamento de pacientes atendidos em unidades de emergências, objetivando uma recuperação precoce e reduzindo o ônus dos serviços de saúde.

Proper Use of Diuretics

Diuretics are among the most commonly used drugs. They primarily block active reabsorption of sodium at different sites in the nephron, thereby increasing urinary losses of NaCl and H2O. This ability to induce a negative fluid balance has made these drugs particularly useful in the treatment of a variety of conditions, edematous: congestive heart failure, nephrotic syndrome, liver cirrhosis, chronic renal failure, idiopathic edema, and nonedematous states: hypertension, hypercalcemia, nephrolithiasis, and syndrome of inappropriate antidiuretic hormone secretion. The diuretics are generally divided into three major classes, which are distinguished by the sites at which they impair the sodium reabsorption: loop diuretics at the thick ascending limb of the loop of Henle, thiazide-type diuretics at the distal tubule, and potassium-sparing diuretics at the cortical collecting tubule. The loop diuretics that are generally the most potent are furosemide, torasemide, and ethacrynic acid. The thiazide-type diuretics include chlorothiazide and metolazone. Spironolactone and amiloride are potassium-sparing diuretics. Diuretics should be started at an effective single dose and given intermittently with a subsequent increase in dose or frequency of administration. As a general rule, the rate of diuresis in an edematous patient should not exceed 1 to 2kg weight loss per day. In renal failure patients, loop diuretics at a higher than normal dose are required to get the desired diuretic effect because the diuretic excretion is often limited, in part due to the retention of organic anions. The patients with liver cirrhosis are responsive to spironolactone. After the administration of diuretics, even if a net diuresis is induced, the response is short-lived as a new steady state is rapidly established because the diuretic-induced sodium losses are counterbalanced by neuro-humorally mediated increases in tubular reabsorption at nondiuretic sensitive sites. This process is called compensatory antidiuresis or diuretic tolerance. Therefore sodium restriction is important when a patient is taking loop diuretics, and the concurrent use of a thiazide diuretic can inhibit downstream NaCl reabsorption, resulting in an exaggeration of diuresis. The most common side-effects are those encountered in virtually all the effective drugs: hypovolemia, hypokalemia and potassium depletion, hyperuricemia, and metabolic alkalosis. Other side-effects include hyperglycemia, hyperlipidemia, hyperuricemia, ototoxicity and sexual dysfunction. In addition, diuretics have the potential to increase the toxicity of several other agents. Nonsteroidal antiinflammatory drugs may antagonize the natriuretic effects of diuretics. The combination of potassium-sparing diuretics and angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers may result in severe hyperkalemia.

Neuroendocrine control of body fluid homeostasis

Angiotensin II and atrial natriuretic peptide (ANP) play important and opposite roles in the control of water and salt intake, with angiotensin II promoting the intake of both and ANP inhibiting the intake of both. Following blood volume expansion, baroreceptor input to the brainstem induces the release of ANP within the hypothalamus that releases oxytocin (OT) that acts on its receptors in the heart to cause the release of ANP. ANP activates guanylyl cyclase that converts guanosine triphosphate into cyclic guanosine monophosphate (cGMP). cGMP activates protein kinase G that reduces heart rate and force of contraction, decreasing cardiac output. ANP acts similarly to induce vasodilation. The intrinsic OT system in the heart and vascular system augments the effects of circulating OT to cause a rapid reduction in effective circulating blood volume. Furthermore, natriuresis is rapidly induced by the action of ANP on its tubular guanylyl cyclase receptors, resulting in the production of cGMP that closes Na+ channels. The OT released by volume expansion also acts on its tubular receptors to activate nitric oxide synthase. The nitric oxide released activates guanylyl cyclase leading to the production of cGMP that also closes Na+ channels, thereby augmenting the natriuretic effect of ANP. The natriuresis induced by cGMP finally causes blood volume to return to normal. At the same time, the ANP released acts centrally to decrease water and salt intake

Changes in Hypothalamic Expressions of Natriuretic Peptide mRNA following Head-down Suspension in Rats

BACKGROUND: Head-down suspension (HDS) of rats has been used as a model for simulation of a microgravity environment. C-type natriuretic peptides (CNP) and atrial natriuretic peptide (ANP) are produced in the central nervous system, especially in hypothalamus, to complement their peripheral natriuretic effects. Therefore, this study investigated the changes in the central adaptations of hypothalamic ANP and CNP syntheses to 4 weeks of HDS in rats. METHODS: Unanesthetized, unrestrained, male Sprague-Dawley rats were subjected to either a horizontal position (control rats) or a -45 degrees head-down tilt using the tail-traction technique (HDS rats). We determined the hypothalamic syntheses of natriuretic peptides as an expression of ANP and CNP mRNA. The expression of natriuretic peptide mRNA was measured by reverse transcription-polymerase chain reaction with [32P]-dCTP following 4 weeks of HDS in the hypothalamus of control and HDS rats. RESULTS: After 4 weeks of HDS, the expression of ANP mRNA showed a decreasing trend in the hypothalamus of HDS rats. In contrast with ANP, CNP mRNA expression was significantly (p<0.01) increased in the hypothalamus of HDS rats. There were different changes in the hypothalamic CNP and ANP mRNA expressions of HDS rats compared with that of the control rats.CONCLUSION: These results represent that the hypothalamic syntheses of natriuretic peptides are differently responded and the role of CNP is augmented to compensate for the decrement of ANP action in the central nervous system following 4 weeks of HDS.

Effects of K+ Channel Opener WAY120491 on Renal Function in Rabbits / 대한신장학회잡지

BACKGROUND: K+ channel opener has been considered as a vasorelaxing agent working through hyperpolarization of vascular smooth muscle cells. Renal tubules-proximal, thick ascending limb of Henle and cortical collecting duct-are the site of the diversity of the K+ channel. ATP-sensitive K+ channel has been observed in the apical membranes of the thick ascending limb of Henle and collecting duct, and basolateral membrane of the proximal tubule. It was also shown that K+ channel opener increased renal hemodynamics and elicited diuretic and natriuretic effects. METHODS: To clarify the renal effects of WAY120491, a K+ channel opener, experiments were performed in unanesthetized normotensive and renal hypertensive rabbits allowing unilateral renal arterial infusion of agent. RESULTS: Intrarenal arterial infusion (0.13, 0.32 and 0.64 microgram/kg/min) of WAY120491 increaased CPAH, CCr, urine volume, UNaV, UKV and CH2O. Renal hemodynamic effects and increments of urine volume and free water clearance were completely blocked by glibenclamide (8.2 g/kg/min), while increments of UNaV and FENa were not significantly affected. Renal hemodynamic and tubular effects of WAY120491 were not significantly different in two-kidney one clip Goldblatt hypertensive rabbits from sham-operated rabbits. CONCLUSIONS: These results suggest that WAY120491 elicits renal effects through ATP-sensitive K+ channel in the renal vasculatures and renal tubules and the renal effects of WAT120491 may not be altered in the hypertension.

Presencia de guanilil ciclasas sensibles a los péptidos natriuréticos ANP y CNP en el músculo liso traqueal de bovino / Guanylyl cyclases sensibility to natriuretic peptide ANP and CNP in the tracheal muscle smooth of bovine

La producción de GMP cíclico en el músculo liso traqueobronquial de bovino (MLTB) es catalizada por guanilil ciclasas soluble (sGC) y particulada (mGC). Para la identificación de la mGC involucrada en la regulación muscarínica, via receptores M2 y M3 del tono de MTLB, se amplificó a partir de cDNA obtenido del MLTB una región conservada en el dominio catalítico de todas las GC. La secuenciación de los productos de RT-PCR reveló que el 76 por ciento de los transcriptos codifican para la subunidad ß1 de sGC y el 24 por ciento para la isoforma B (sensible al péptido CNP) de la mGc. RT-PCRs con oligonucléotidos isoforma-específicos mostraron que las isoformas sensibles a los péptidos ANP y guanilina también se expresan en el MLTB. La activación máxima de mGC obtenida con CNP resultó significativamente (p<0.001) superior a la lograda con ANP, indicando que la isoforma B es la mGC predominante en este tejido

Effects of Intrarenal Arterial Infusion of Atrial Natriuretic Peptide Analogs on Renal Function in Unanesthetized Rabbits / 대한신장학회잡지

BACKGROUND: Atrial cardiomyocytes synthesize, store and release atrial natriuretic peptide(ANP) which has potent physiological effects, including natriuresis, diuresis, relaxation of vascular smooth muscle and inhibition of aldosterone and renin secretion. A family of atrial peptides are derived from a precursor proANP. However, the structure-activity relationship of several C-terminal ANPs are not yet well documented. METHODS: The effects of structural difference of ANP analogs on the renal function were studied with a sensitive and reproducible bioassay using intrarenal arterial infusion in unanesthetized rabbits. RESULTS: Rat ANP-(1-28)(rANP, 12-Ile), a-human ANP-(1-28)(hANP, 12-Met), atriopeptin III [APIII, rANP-(5-28)], atriopeptin II[APII, rANP-(5- 27)], atriopeptin I[API, rANP-(5-25)], a-human ANP- (7-28)[hANP-(7-28)], and ANP fragments(13-28) [ANP-(13-28)] and (17-28)[ANP-(17-28)] were infused into left renal artery. No significant differences were observed between rANP and hANP. Diuretic and natriuretic activities of APIII were significantly lower than those of rANP and hANP, but were similar to those of hANP-(7-28). Diuretic and natriuretic effects of APII were similar to rANP and hANP in terms of peak responses. Duration of the effects of APII were longer than those of rANP and hANP. No significant changes were observed by infusions of API, and ANP fragments, ANP-(13-28) and ANP-(17-28). rANP, hANP and APIII decreased active but increased inactive renin secretion. CONCLUSION: These data suggest that substitution of isoleucine to methionine at 12 position of ANP does not affect the renal effects of ANP and that disulfide bond and C-terminal segment of ANP are important for the possession of natriuretic and diuretic activities.

effect of 72 hours' continuous infusion of long acting natriuretic peptide on acute ischemic renal failure in the rat

Atrial natriuretic peptide [ANP1-28] protects the kidneys against acute renal failure in animals; however, its use in humans has been disappointing. Long acting natriuretic peptide [LANP1-30] has natriuretic and diuretic actions similar to ANP1-28, but it has a longer halflife and a diff e rent receptor site of action. These differences comprise this study, specifically, to see if LANP1-30 has better renal protection than ANP1-28, which may make it useful in the treatment of acute renal failure. Subjects/Three groups of male Sprague- Dawley rats were used, each with a body weight between 250-300 gm. Group 1 [ischemia only, n=6] had right nephrectomy followed by 30 minutes of left renal pedicle clamping. Group 2 [LANP Peptide treated, n=7] had renal ischemia similar to Group 1, followed by an intraperitoneal bolus of 10 mg of LANP1-30 and placement of mini-osmotic pumps delivering LANP1-30 at a rate of 1mg/hr for 72 hours. Group 3 [controls, n=6] was used to measure the baseline creatinine level and had no renal ischemia or surgery. 72 hours post renal ischemia, the weight loss in the ischemia group was similar to the peptide treated group [7.65 +/- 1.14% and 10.03 +/- 0.9% body weight loss, re s p e c t i v e l y, p=0.126]. The ischemia group had significantly higher creatinine levels compared to the controls [66.3 +/- 5.3 versus 30.1 +/- 0.9 mmol/l, p=0.002]. The peptide treated group had higher creatinine [174.1 +/- 77.8 versus 66.3 +/- 5.3 mol/l, p=0.035] and LANP1-30 levels [673.14 +/- 69.64 versus 45.83 +/- 8.45 pg/ml, p=0.001] than the ischemia group. Prolonged use of LANP1-30 has no renal protective effect

Effects of Intrarenal Arterial Infusion of Arginine Vasopressin on the Renal Function and Renin Release in Conscious Rabbits / 대한신장학회잡지

Arginine vasopressin(AVP) released from the posterior pituitary gland is well known to cause an increase in blood pressure, antidiuresis, natriuresis and inhibition of renin secretion. However, the mechanism involved in AVP-induced natriuresis is still unknown. To investigate the mechanism of AVP- induced natriuresis, different doses of AVP were infused into the left renal artery for 10 min and renal function and data were obtained in unanesthetized rabbits. Infusion of different doses of AVP (0.3pg/kg/min-10,000pg/kg/min) caused marked decreases in urine volume, renal blood flow, glomerular filtration rate and free water clearance without changes in blood pressure. Changes in renal function by AVP were not dose-dependent but it took more time for the renal function to recover with increasing doses. Infusion of large doses of AVP(3,000, 10,000pg/kg/min) caused increases in sodium excretion in both kidneys without changes in blood pressure. Infusion of AVP caused a decrease in renin secretion rate. In indomethacin-treated rabbits, changes in urine volume and renal hemodynamics by AVP were markedly accentuated whereas natriuretic effects were attenuated. However, a marked natriuresis caused by AVP in control right kidney still persistently existed. These results suggest that the AVP-induced natriuresis may occur in two-different ways: one is indirect hormonal including prostaglandins and the other is tubular.

Studies on the Mechanism of Renal Action of Centrally-administered TFMPP in Rabbits / 대한신장학회잡지

It has been known that central tryptaminergic system is closely related with the regulation of renal function, and that central 5-HT1 receptors mediate diuresis and natriuresis, whereas central 5-HT2 and 5-HT3 receptors mediate antidiuresis and antinatriuresis. Among many subtypes of 5-HT1 receptors, central 5-HT1A subtype has been suggested to exert diuretic and natriuretic effets. Further, it was recently observed that TFMPP, 5-HT1B agonist, elicited profound diuresis and natriuresis when administered intracerebroventricularly(icv). Present study is therefore undertaken to delineate the mechanism involved in the natriuresis and diuresis induced by icv TFMPP, employing the denervated and vagotomized rabbits. The influence of icv TFMPP on the plasma level of ANP was also observed. TFMPP 250 microgram/kg icv produced marked diuresis and natriuresis. Renal hemodynamics showed significant increase only in the first 10-min period after administration and thereafter tended to recover. However, natriuretic action lasted even after the increased renal hemodynamics returned to the control level, suggesting the decreased Na reabsorption in the tubules by humoral natriuretic factors. Systemic blood pressure transiently increased. In rabbits in which one kidney is denervated, with the contralateral intact as the control kidney, the denervated kidney also responded with natriuresis and diuresis like that of the normal rabbit. The contralateral kidney responded with typical diuretic and natriuretic effects, along with the marked increased of renal hemodynamics. The plasma ANP, one of humoral natriuretic factors, increased after administration of icv TFMPP, peaking at about 15min. In bilaterally vagotomized rabbits, the natriuretic and diuretic effects produced by icv TFMPP were greater than that of the normal rabbits. These observations suggest that the natriuresis and diuresis elicited by icv TFMPP result from the inhibition of tubular Na reabsorption mainly through mediation of ANP. It has been also suggested that vagus nerve might exert inhibitory influence on the diuretic action of icv TFMPP, because the renal effects was augmented in the vagotomized rabbits.

Influence of Intracerebroventricular Kallikrein and Lys-bradykinin on the Rabbit Renal Function / 대한신장학회잡지

The renal function is under regulatory influence of central nervous system, in which various neurotransmitter and neuromodulator systems take part, and it has been known that kallikrein-kininogen- kinin system exists also in the brain, but its physiological role remains to be explored. This study was, therefore, undertaken to delineate the possible role of central kinin system in the regulation of renal function. Kallikrein given into a lateral ventricle(icv) of rabbit brain in doses ranging from 3 to 30 microgram/kg icv elicited increases in Na excretion and the fraction of filtered sodium excreted(FENa), as well as in urine flow rate. K excretion, however, did not parallel the Na excretion, but tended to decrease when the natriuresis reached its peak. Renal blood flow and glomerular filtration did not significantly change. Neither did free water reabsorption significantly change, but tended to decrease. The systemic blood pressure slightly increased. When 30 microgram/kg kallikrein was given intravenously, all the parameters of renal function and systemic blood pressure did not show any increase but decrease, primarily by decreased renal hemodynamics, resulting from transient hypotension. In experiments in which the plasma ANP was measured, the ANP level markedly increased, reaching more than 5 times the control value 25min after 30 microgram/kg icv, and lasting until the end of the experiment at 80min. The renal nerve activity increased with kallikrein, 30 microgram/kg icv, peaking at 1 min but it remained slightly increased until about 40 min, and then slightly declined. This indicates that the increased renal nerve activity may have antagonized or ameliorated the natriuretic effect of icv kallikrein. Lys-bradykinin(kallidin), a cleavage product from kallidinogen by kallikrein, when given icv in doses of 0.3 to 30 microgram/kg also produced increased Na excretion and diuresis. When CHA, a kallikrein inhibitor, was given icv in doses of 3-30 microgram/kg, elicited antidiuresis and antinatriuresis. However, pretreatment with CHA tended slightly to suppress the kallikrein effect. These results indicate that the central kallikrein- kinin system is involved in the central regulation of renal function, the activation of the system in the CNS resulting in increased natriuresis and diuresis, which are related to increased plasma ANP level, with the possible antagonistic effects of increased renal nerve activity.