Effects of angiotensin peptides on colonic motility in rats

Purpose@#Renin-angiotensin system (RAS) is involved in the pathophysiology of colonic inflammation. The aim of this study was to investigate whether small angiotensins (Angs) peptides play a role in the regulation of colonic motility and their roles are modulated in colitis. @*Methods@#Experimental colitis was induced by an intake of 5% dextran sulfate sodium (DSS) dissolved in tap water for 7 days in Sprague-Dawley rats. After sacrifice, plasma hormone concentrations and messenger RNAs (mRNAs) for RAS were measured. Functional analysis of colonic motility in response to Angs peptides was performed using Taenia coli. @*Results@#DSS-treated colon showed an increased necrosis with massive infiltration of inflammatory cells. The mRNA level of colonic angiotensin II receptor type 2 (AT2R) in DSS-treated rats was higher than that in control rats whereas the mRNA levels of angiotensin II converting enzyme (ACE), ACE2, AT1R, AT4R, and Mars receptor were not different from those in control rats. Ang III, Ang IV, and Ang-(1-9) (1, 3 μM) increased the frequency of basal colonic motility. Ang-(1-7) did not cause any significant changes in frequency and amplitude of basal motility. The order of potency for an increased frequency of basal motility seems to be Ang II>>Ang IV>Ang III=Ang-(1-9). The increased frequency of basal motility by Ang-(1-9) but not Ang IV was significantly enhanced in DSS-treated rat colon. @*Conclusion@#In conclusion, these data suggest that small Angs peptides are partly involved in the pathophysiological regulation of colonic motility in experimental colitis.

Carbon monoxide releasing molecule-2 suppresses stretchactivated atrial natriuretic peptide secretion by activating largeconductance calcium-activated potassium channels

Carbon monoxide (CO) is a known gaseous bioactive substance found across a wide array of body systems. The administration of low concentrations of CO has been found to exert an anti-inflammatory, anti-apoptotic, anti-hypertensive, and vaso-dilatory effect. To date, however, it has remained unknown whether CO influences atrial natriuretic peptide (ANP) secretion. This study explores the effect of CO on ANP secretion and its associated signaling pathway using isolated beating rat atria. Atrial perfusate was collected for 10 min for use as a control, after which high atrial stretch was induced by increasing the height of the outflow catheter. Carbon monoxide releasing molecule-2 (CORM-2; 10, 50, 100 µM) and hemin (HO-1 inducer; 0.1, 1, 50 µM), but not CORM-3 (10, 50, 100 µM), decreased high stretch-induced ANP secretion. However, zinc porphyrin (HO-1 inhibitor) did not affect ANP secretion. The order of potency for the suppression of ANP secretion was found to be hemin > CORM-2 >> CORM-3. The suppression of ANP secretion by CORM-2 was attenuated by pretreatment with 5-hydroxydecanoic acid, paxilline, and 1H-[1,2,4] oxadiazolo [4,3-a] quinoxalin-1-one, but not by diltiazem, wortmannin, LY-294002, or NG-nitroL-arginine methyl ester. Hypoxic conditions attenuated the suppressive effect of CORM-2 on ANP secretion. In sum, these results suggest that CORM-2 suppresses ANP secretion via mitochondrial K ATP channels and large conductance Ca 2+ -activated K+ channels.

Angiotensin-(1-9) ameliorates pulmonary arterial hypertension via angiotensin type II receptor

Angiotensin-(1-9) [Ang-(1-9)], generated from Ang I by Ang II converting enzyme 2, has been reported to have protective effects on cardiac and vascular remodeling. However, there is no report about the effect of Ang-(1-9) on pulmonary hypertension. The aim of the present study is to investigate whether Ang-(1-9) improves pulmonary vascular remodeling in monocrotaline (MCT)-induced pulmonary hypertensive rats. Sprague-Dawley rats received Ang-(1-9) (576 µg/kg/day) or saline via osmotic mini-pumps for 3 weeks. Three days after implantation of osmotic mini-pumps, 50 mg/kg MCT or vehicle were subcutaneously injected. MCT caused increases in right ventricular weight and systolic pressure, which were reduced by co-administration of Ang-(1-9). Ang-(1-9) also attenuated endothelial damage and medial hypertrophy of pulmonary arterioles as well as pulmonary fibrosis induced by MCT. The protective effects of Ang-(1-9) against pulmonary hypertension were inhibited by Ang type 2 receptor (AT₂R) blocker, but not by Mas receptor blocker. Additionally, the levels of LDH and inflammatory cytokines, such as TNF-α, MCP-1, IL-1β, and IL-6, in plasma were lower in Ang-(1-9) co-treated MCT group than in vehicle-treated MCT group. Changes in expressions of apoptosis-related proteins such as Bax, Bcl-2, Caspase-3 and -9 in the lung tissue of MCT rats were attenuated by the treatment with Ang-(1-9). These results indicate that Ang-(1-9) improves MCT-induced pulmonary hypertension by decreasing apoptosis and inflammatory reaction via AT₂R.

Comparative effects of angiotensin II and angiotensin-(4-8) on blood pressure and ANP secretion in rats

Angiotensin II (Ang II) is metabolized from N-terminal by aminopeptidases and from C-terminal by Ang converting enzyme (ACE) to generate several truncated angiotensin peptides (Angs). The truncated Angs have different biological effects but it remains unknown whether Ang-(4-8) is an active peptide. The present study was to investigate the effects of Ang-(4-8) on hemodynamics and atrial natriuretic peptide (ANP) secretion using isolated beating rat atria. Atrial stretch caused increases in atrial contractility by 60% and in ANP secretion by 70%. Ang-(4-8) (0.01, 0.1, and 1 µM) suppressed high stretch-induced ANP secretion in a dose-dependent manner. Ang-(4-8) (0.1 µM)-induced suppression of ANP secretion was attenuated by the pretreatment with an antagonist of Ang type 1 receptor (AT₁R) but not by an antagonist of AT₂R or AT₄R. Ang-(4-8)-induced suppression of ANP secretion was attenuated by the pretreatment with inhibitor of phospholipase (PLC), inositol triphosphate (IP₃) receptor, or nonspecific protein kinase C (PKC). The potency of Ang-(4-8) to inhibit ANP secretion was similar to Ang II. However, Ang-(4-8) 10 µM caused an increased mean arterial pressure which was similar to that by 1 nM Ang II. Therefore, we suggest that Ang-(4-8) suppresses high stretch-induced ANP secretion through the AT₁R and PLC/IP₃/PKC pathway. Ang-(4-8) is a biologically active peptide which functions as an inhibition mechanism of ANP secretion and an increment of blood pressure.

Inhibition of Janus activated kinase-3 protects against myocardial ischemia and reperfusion injury in mice

Recent studies have documented that Janus-activated kinase (JAK)-signal transducer and activator of transcription (STAT) pathway can modulate the apoptotic program in a myocardial ischemia/reperfusion (I/R) model. To date, however, limited studies have examined the role of JAK3 on myocardial I/R injury. Here, we investigated the potential effects of pharmacological JAK3 inhibition with JANEX-1 in a myocardial I/R model. Mice were subjected to 45 min of ischemia followed by varying periods of reperfusion. JANEX-1 was injected 1 h before ischemia by intraperitoneal injection. Treatment with JANEX-1 significantly decreased plasma creatine kinase and lactate dehydrogenase activities, reduced infarct size, reversed I/R-induced functional deterioration of the myocardium and reduced myocardial apoptosis. Histological analysis revealed an increase in neutrophil and macrophage infiltration within the infarcted area, which was markedly reduced by JANEX-1 treatment. In parallel, in in vitro studies where neutrophils and macrophages were treated with JANEX-1 or isolated from JAK3 knockout mice, there was an impairment in the migration potential toward interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1), respectively. Of note, however, JANEX-1 did not affect the expression of IL-8 and MCP-1 in the myocardium. The pharmacological inhibition of JAK3 might represent an effective approach to reduce inflammation-mediated apoptotic damage initiated by myocardial I/R injury.

Altered Regulation of Renal Acid Base Transporters in Response to Ammonium Chloride Loading in Rats

The role of the kidney in combating metabolic acidosis has been a subject of considerable interest for many years. The present study was aimed to determine whether there is an altered regulation of renal acid base transporters in acute and chronic acid loading. Male Sprague-Dawley rats were used. Metabolic acidosis was induced by administration of NH4Cl for 2 days (acute) and for 7days (chronic). The serum and urinary pH and bicarbonate were measured. The protein expression of renal acid base transporters [type 3 Na+/H+ exchanger (NHE3), type 1 Na+/HCO3- cotransporter (NBC1), Na-K+ ATPase, H(+)-ATPase, anion exchanger-1 (AE-1)] was measured by semiquantitative immunoblotting. Serum bicarbonate and pH were decreased in acute acid loading rats compared with controls. Accordingly, urinary pH decreased. The protein expression of NHE3, H(+)-ATPase, AE-1 and NBC1 was not changed. In chronic acid loading rats, serum bicarbonate and pH were not changed, while urinary pH was decreased compared with controls. The protein expression of NHE3, H(+)-ATPase was increased in the renal cortex of chronic acid loading rats. These results suggest that unaltered expression of acid transporters combined with acute acid loading may contribute to the development of acidosis. The subsequent increased expression of NHE3, H(+)-ATPase in the kidney may play a role in promoting acid excretion in the later stage of acid loading, which counteract the development of metabolic acidosis.

Decreased Expression of Na+/K+-ATPase, NHE3, NBC1, AQP1 and OAT in Gentamicin-induced Nephropathy

The present study was aimed to determine whether there is an altered regulation of tubular transporters in gentamicin-induced nephropathy. Sprague-Dawley male rats (200~250 g) were subcutaneously injected with gentamicin (100 mg/kg per day) for 7 days, and the expression of tubular transporters was determined by immunoblotting and immunohistochemistry. The mRNA and protein expression of OAT was also determined. Gentamicin-treated rats exhibited significantly decreased creatinine clearance along with increased plasma creatinine levels. Accordingly, the fractional excretion of sodium increased. Urine volume was increased, while urine osmolality and free water reabsorption were decreased. Immunoblotting and immunohistochemistry revealed decreased expression of Na+/K+-ATPase, NHE3, NBC1, and AQP1 in the kidney of gentamicin-treated rats. The expression of OAT1 and OAT3 was also decreased. Gentamicin-induced nephropathy may at least in part be causally related with a decreased expression of Na+/K+-ATPase, NHE3, NBC1, AQP1 and OAT.

Different Regulation of Atrial ANP Release through Neuropeptide Y2 and Y4 Receptors

Neuropeptide Y (NPY) receptors are present in cardiac membranes. However, its physiological roles in the heart are not clear. The aim of this study was to define the direct effects of pancreatic polypeptide (PP) on atrial dynamics and atrial natriuretic peptide (ANP) release in perfused beating atria. Pancreatic polypeptides, a NPY Y4 receptor agonist, decreased atrial contractility but was not dose-dependent. The ANP release was stimulated by PP in a dose-dependent manner. GR 23118, a NPY Y4 receptor agonist, also increased the ANP release and the potency was greater than PP. In contrast, peptide YY (3-36) (PYY), an NPY Y2 receptor agonist, suppressed the release of ANP with positive inotropy. NPY, an agonist for Y1, 2, 5 receptor, did not cause any significant changes. The pretreatment of NPY (18-36), an antagonist for NPY Y3 receptor, markedly attenuated the stimulation of ANP release by PP but did not affect the suppression of ANP release by PYY. BIIE0246, an antagonist for NPY Y2 receptor, attenuated the suppression of ANP release by PYY. The responsiveness of atrial contractility to PP or PYY was not affected by either of the antagonists. These results suggest that NPY Y4 and Y2 receptor differently regulate the release of atrial ANP.

Role of Gap Junction in the Regulation of Renin Release and Intracellular Calcium in As 4.1 Cell Line

Gap junction protein, connexin, is expressed in endothelial cells of vessels, glomerulus, and renin secreting cells of the kidney. The purpose of this study was to investigate the role of gap junction in renin secretion and its underlying mechanisms using As 4.1 cell line, a renin-expressing clonal cell line. Renin release was increased proportionately to incubation time. The specific gap junction inhibitor, 18-beta glycyrrhetinic acid (GA) increased renin release in dose-dependent and time- dependent manners. Heptanol and octanol, gap junction blockers, also increased renin release, which were less potent than GA. GA-stimulated renin release was attenuated by pretreatment of the cells with amiloride, nifedipine, ryanodine, and thapsigargin. GA dose-dependently increased intracellular Ca2+ concentration, which was attenuated by nifedipine, nimodipine, ryanodine, and thapsigargin. However, RP-cAMP, chelerythrine, tyrphostin A23, or phenylarsine oxide did not induced any significant change in GA-stimulated increase of intracellular Ca2+ concentration. These results suggest that gap junction plays an important role on the regulation of renin release and intracellular Ca2+ concentration in As 4.1 cells.

Increased Expression of Endothelin-1 and CYP11B2 in Gentamicin-Induced Nephropathy in Rat Kidney / 대한신장학회지

PURPOSE: An altered activity of vasoactive hormones as well as aldosterone synthase (CYP11B2) in the kidney may involve the pathogenesis of gentamicin-induced nephropathy. The present study was designed to investigate whether there are changes of local renin-angiotensin-aldosterone system (RAAS) and endothelin (ET) in the kidney of gentamicin-induced nephropathy in rats. METHODS: Male Sprague-Dawley rats (180-200 g) were intramuscularly injected with gentamicin (100 mg/kg per day) for 5 days. Vehicle was given for the control rats. The mRNA expression of local renin-angiotensin system, aldosterone synthase (CYP11B2), ET system and transforming grow factor-beta1 (TGF-beta1) was determined in the kidney by real-time polymerase chain reaction. The protein expression of TGF-beta in the kidney was determined by immunoblotting and immunohistochemistry. RESULTS: Following the gentamicin treatment, a renal failure was noted as evidenced by increased serum concentrations of creatinine along with a decrease of its clearance. TGF-beta1 expression was significantly increased in the kidney in gentamicin treated rats compared with that in controls. The abundance of ET-1 mRNA was significantly increased. The endothelin type A receptor expression was decreased while endothelin type B receptor was not changed. The expression of angiotensin converting enzyme 1 (ACE1) and ACE2 was decreased, whereas renin expression was not changed. The CYP11B2 expression was significantly increased in gentamicin treated rats, while mineralocorticoid receptor expression was not changed. CONCLUSION: The expression of ET-1 and CYP11B2 was up-regulated which may play a role in the pathogenesis of gentamicin-induced nephropathy.

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.

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.

Roles of Calcium in Regulation of ANP Secretion / 대한신장학회잡지

No abstract available.

Renal Effects of Intrarenal Norepinephrine in the Nonclipped Kidney of Two-kidney, One Clip Goldblatt Hypertensive Rabbits / 대한신장학회잡지

Roles of the nonclipped kidney in the development and maintenance of the high blood pressure in two- kidney, one clip hypertension remain to be defined. It has been known that the pathophysiology of hypertension is different by the presence or absence of the contralateral kidney in renal hypertension. The present study was undertaken to evaluate the effects of intrarenal norepinephrine in the nonclipped kidney exposed to the high blood pressure. Experiments were performed in 7-day two-kidney, one clip Goldblatt hypertensive and sham-operated normotensive rabbits. The basal levels of renal plasma flow and urine flow, and urinary excretion of electrolytes were higher in the nonclipped kidney of two-kidney, one clip Goldblatt hypertensive than in the corresponding kidney of sham-operated normotensive rabbits. Intrarenal infusion of norepinephrine increased renal perfusion resistance, and decreased renal hemodynamics and renal excretory function in a dose-dependent manner in both hypertensive and normotensive rabbits. The renal hemodynamics and excretory responses to intrarenal norepinephrine infusion were attenuated in two-kidney, one clip Goldblatt hypertensive rabbits. The changes by norepinephrine infusion of the renal excretory function were closely correlated with those in glomerular filtration rate or renal plasma flow. These results suggest that the impaired vascular reactivity in the nonclipped kidney is one of the early changes appeared in the course of multifactorial derangements in renal hypertension and that the impairment may be an adaptive response of the kidney to high blood pressure.

Characteristics of Norepinephrine Induced Natriuresis in Rabbits / 대한신장학회잡지

No abstract available.

Postnatal changes in atrial compliance and stretch-induced ANP secretion in rabbits

To define the postnatal changes in ANP secretion in response to mechanical stretch and atrial compliance, experiments have been done in perfused nonbeating rabbit atria with different ages: 1-day, 1-, 2-, 3-, 4-, and 8-wk-old. In 1-day-old-rabbits, an increase in intraatrial pressure resulted in an increase in atrial volume, which was higher than that in 1-wk-old rabbits. Increases in atrial volume stimulated the secretion of ANP with concomitant translocation of extracellular fluid (ECF) into the atrial lumen. However, mechanically stimulated ECF translocation was lower in 1-day-old rabbits than that in 1-wk-old rabbits. Therefore, positive relationship between mechanically stimulated ECF translocation and ANP secretion was shifted upward in 1-day-old rabbits, as compared to 1-wk-old rabbits. Changes in atrial volume and ECF translocation were gradually increased with aging and reached the peak value at 4 wk. The stretch-induced ANP secretion in terms of ECF translocation (the interstitial ANP concentration) was also increased with aging and reached the peak value at 4 wk. The interstitial ANP concentration was dependent on the atrial content of ANP. These data suggest that the higher level of atrial ANP secretion is related to the postnatal changes in atrial volume and unidentified factor.

Effect of Arginine Vasotocin on the Rabbit Renal Function / 대한신장학회잡지

Arginine vasotocin has long been known as an antidiuretic hormone in non-mammalian vertebrates. The peptide has also been found in mammalian tissues. The physiological significance of the peptide, however, has not yet been clarified in mammals. To define the effect of arginine vasotocin on the water and electrolyte balance in mammalian vertebrates, experiments have been done. Intrarenal arterial infusion of arginine vasotocin, 0.01-10ng/kg/min resulted in dose-dependent decreases in urine volume and free water clearance and an increase in urinary osmolarity. Arginine vasotocin, in a dose of 0.03ng/kg/min, induced an increase in water reabsorption without changes in glomerular filtration rate. Intrarenal infusion of arginine vasotocin in doses ranging from 0.1 to 3.0 or 10.0ng/kg/min resulted in decreases in glomerular filtration rate and renal plasma flow. However, no dose dependence were observed. Intrarenal infusion of arginine vasotocin from 0.3 to 10 ng/kg/min induced dose-dependent natriuretic and kaliuretic effects with concomitant suppression of renin secretion. The renal effects of arginine vasotocin were blocked by arginine vasopressin V2-receptor antagonist [d(CH2)5, D-Phe2, Ile4, Ala9-NH2]-vasopressin but were not blocked by[d(CH2)5, D-Ile2, Ile4, Arg8]- vaso pression. These data suggest that the effect of arginine vasotocin on the renal function are similar to that of vasopressin in mammalian vertebrates. The data also suggest that the renal effects of arginine vasotocin may be coupled to the receptor system which is similar, if not identical, to that of arginine vasopressin.

Effects of Extremely Low Doses of Arginine Vasopressin on the Renal Function in Two-kidney One Clip Goldblatt Hypertensive Rabbit / 대한신장학회잡지

It has been suggested that arginine vasopressin is involved in the acute, but not chronic, regulation of blood pressure. It is still debatable on the role of arginine vasopressin in the development and maintenance of high blood pressure, especially in renal hypertension. This study was performed to examine antidiuretic and renal hemodynamic effects of extremely low doses of arginine vasopressin and the modification of the effects in the early phase of two-kidney one clip Goldblatt hypertensive rabbits. Very low doses(up to 10-20mole/kg/min) of intrarenal arginine vasopressin induced decreases in urine volume, free water clearance, glomerular filteration rate and renal plasma flow(CPAH). The renal effects of arginine vasopressin were dose-dependent. These data indicate that the sensitivity of the kidney to decrease urine volume in response to arginine vasopressin is at least three orders of magnitude higher than previously reported. The renal effects of arginine vasopressin was significantly attenuated by the pretreatment of V2-receptor antagonist. The antidiuretic and renal hemodynamic effects elicited by very low doses of intrarenal arginine vasopressin were suppressed in the contralateral unclipped kidney of two-kidney, one clip Goldblatt hypertensive rabbits. These data suggest that the renal functions can be regulated normally by an extremely low concentration of plasma arginine vasopressin and the regulatory mechanism controlled by the ultralow plasma levels of arginine vasopressin is suppressed in the early phase of two-kidney, one clip Goldblatt hypertension.

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.

Effects of Acetylcholine on the Renal Function in Renal Hypertensive Rabbits / 대한신장학회잡지

It has long been known that acetylcholine infusion resulted in increases in urine volume, urinary excretion of Na and renal plasma flow. Exact mechanism of renal effects of acetylcholine, however, has not yet been clarified. Since the discovery of endothelium-derived relaxing factor/nitric oxide system, the vascular endothelium has been considered as an endocrine gland. The purpose of the present study was to define the effect of acetylcholine on the renal hemodynamic and tubular function, and the modification of the renal effects of acetylcholine in two- kidney one clip Goldblatt hypertensive rabbits. Intrarenal acetylcholine(0.03-0.3ug/kg/min) increased glomerular filtration rate(GFR, CCr), renal plasma flow (RPF, CPAH), urine volume(UV), free water clearance (CH2O), urinary excretion of electrolytes(UNaV, UKV) and nitrate(UNO3V) and fractional excretion of Na+ (FENa) in unanesthetized rabbits. No change in filtration fraction was observed. Pretreatment with N omega- nitro-L-arginine methyl ester(L-NAME) blocked the acetylcholine-induced renal effects. Acetylcholine infused into the contralateral kidney elicited increases in GFR, RPF, UV, CH2O, UNaV, UKV, UNO3V and FENa in hypertensive rabbits. The hemodynamic effect was not different between normotensive sham-operated and unilateral nephrectomized rabbits. Acetylcholine-induced tubular effect, however, was significantly accentuated in hypertensive rabbits. Neither the renal hemodynamic nor tubular effects of acetylcholine were observed with pretreatment of L-NAME. These results suggest that the renal tubular effect as well as hemodynamic effect of acetylcholine is mediated through the NO system and that the tubular effect of acetylcholine is accentuated in the early phase of renal hypertension.