Intact kidney function during contralateral renal artery clamping in dogs.

Experiments were carried out on 32 Nembutal anaesthetized mongrel dogs from both sexes. After 45 min control period unilateral renal ischemia was achieved by clamping the left renal artery for 90 min. In part of the experiments (n = 8) after clamp removal 3 consecutive 45 min periods were performed. The function of the intact right kidney was investigated. Mean arterial pressure (MAP), heart rate (HR), glomerular filtration rate (GFR), urine flow rate (V), fractional excretions of sodium (FENa), potassium (FEK) and chloride (FECl) and plasma levels of atrial natriuretic peptide, dopamine and antidiuretic hormone were evaluated. During ischemia MAP was elevated from 122.5 +/- 3.1 to 140.2 +/- 2.7 mmHg (p < 0.001), HR decreased from 119 +/- 4 to 102.5 +/- 3.9 beats/min (p < 0.01) as compared to the control period. GFR did not change significantly, while all excretory parameters increased: V from 8.7 +/- 1.2 to 14.5 +/- 1.7 microliters/min/gr kidney tissue (p < 0.05); FENa from 2.3 +/- 0.2 to 3.6 +/- 0.3% (p < 0.01); FEK from 40.0 < 3.5 to 51.2 < 2.8% (p < 0.05); FECl from 1.8 < 0.3 to 2.6 < 0.3% (p < 0.05). MAP remained elevated in the first and the second postischemic periods and was paralleled by the sustained increase in FENa and FECl, while FEK remained higher to the end of the experiment. ANP was significantly elevated during ischemia: on 75 min--p < 0.01 and on 105 min.--p < 0.05. AVP and dopamine showed no statistically significant changes during the investigated periods.(ABSTRACT TRUNCATED AT 250 WORDS)     

Renal effects of atrial natriuretic factor in domestic fowl

The renal hemodynamic and tubular effects of ANF were investigated using the Sperber technique in chickens. This technique takes advantage of the unique portal circulation of the avian kidney and permits direct access to the renal peritubular space independent of renal arterial blood flow and glomerular filtration. Infusion of ANF into the avian renal portal system increased urine flow rate and sodium excretion by as much as 300% and 100%, respectively. These changes occurred in the absence of significant alterations in glomerular filtration rate or renal plasma flow. There was no significant difference in urine flow, sodium excretion or glomerular filtration rate between the ANF-infused kidney and the contralateral, non-infused kidney. We conclude that the diuretic and natriuretic effects of ANF do not depend on changes in glomerular filtration rate and that the site of action of ANF is the renal medulla.     

The effect of dipyridamole on the initiation phase of postischemic acute renal failure in rats

Several previous observations support the hypothesis that increased adenosine production and release mediate, at least in part, the reductions in renal blood flow and glomerular filtration rate in ischemic acute renal failure (ARF). If this hypothesis is correct, dipyridamole should potentiate these changes, since it blocks cellular adenosine uptake, thereby increasing the concentration and potentiating the effects of extracellular adenosine. Moreover, theophylline should block the effects of dipyridamole, since it is an adenosine receptor antagonist. These predictions were tested in three groups of anesthetized rats. All rats were subjected to 30 min of left renal artery occlusion; 30 min after relieving the occlusion, a 45-min clearance period was begun. The control group was given saline i.v.; the two experimental groups received either dipyridamole (24 micrograms X min-1 X kg-1) or dipyridamole plus theophylline i.v. (111 mumol/kg as a prime, 1.1 mumol X min-1 X kg-1 as an infusion). In the control group, the previously ischemic left kidneys exhibited decreased clearances of para-aminohippurate and inulin (CPAH and CIn), filtration fraction (FF), and urine/plasma inulin concentration (U/PIn), and increased urine flow (V), Na excretion (UNaV), and fractional Na excretion (FENa) in comparison with the contralateral right kidney. Dipyridamole pretreatment did not affect the right kidney, but it intensified the reductions in left kidney CPAH, CIn, and FF. Theophylline blocked all these effects of dipyridamole on the left kidney, and increased renal plasma flow (CPAH/PAH extraction), despite a decrease in systemic arterial blood pressure. These results are further support for the hypothesis that adenosine mediates, at least in part, the hemodynamic changes in postischemic ARF in rats.     

Effect of felodipine on renal hemodynamics and excretion in the dog

The effects of felodipine on renal hemodynamics and excretion were evaluated in the anesthetized dog. Unilateral renal arterial infusion of felodipine produced ipsilateral increases in the absolute and fractional excretion of sodium and water which were greater than those of potassium; these effects occurred in the absence of changes in mean arterial pressure, renal blood flow, or glomerular filtration rate. There were no significant effects on renal hemodynamic or excretory function in the contralateral kidney. The unilateral renal arterial infusion of isotonic saline or vehicle produced no significant effects on renal hemodynamic or excretory function in either ipsilateral or contralateral kidney. Felodipine, a calcium antagonist with vasodilator antihypertensive properties, in doses which do not affect systemic or renal hemodynamics in the dog, increased urinary flow rate and sodium excretion by decreasing renal tubular water and sodium reabsorption. As a vasodilator antihypertensive agent, felodipine possesses potentially advantageous diuretic and natriuretic properties.     

Renal effects of dopamine and ANP in high volume expanded rats

Both dopamine (DA) and atrial natriuretic peptide (ANP) have been postulated to exert similar effects on the kidney, participating in the regulation of body fluid and sodium homeostasis. In the present study, experiments were performed in anesthetized and isotonic sodium chloride volume expanded rats. After acute volume expansion at 15 % of body weight during 30 min, glomerular filtration rate, urine output, sodium excretion, fractional sodium excretion, proximal and distal sodium excretion and blood pressure were measured. In additional groups we administered ANP or haloperidol or the combination of both to volume expanded animals. Blockade of DA receptors with haloperidol, attenuated diuretic and natriuretic responses to volume load. Proximal sodium excretion was not modified by haloperidol in all experimental groups of rats. Reduction in distal tubular excretion was induced by haloperidol in saline infusion expanded rat but not in ANP treated expanded animals. In conclusion, when exaggerated volume expansion is provoked, both DA and ANP exert renal tubular events, but ANP have a major central role in the regulation of renal sodium handling.     

Hormonal, renal, hemodynamic responses to acute neutral endopeptidase inhibition in heart transplant patients.

We investigated the hemodynamic, renal, and hormonal responses to neutral endopeptidase (NEP) inhibition during a 6-h, double-blind, randomized, placebo-controlled study in seven chronic, stable heart transplant patients. Baseline characteristics were similar during both experiments, and no significant changes were observed after placebo. NEP inhibition increased circulating endothelin-1 (from 2.01 +/- 0.1 to 2.90 +/- 0.2 pmol/l; P < 0.01), atrial natriuretic peptide (ANP; from 21.5 +/- 2.7 to 29.6 +/- 3.7 pmol/l; P < 0.01), and the ANP second messenger cGMP. Noteworthy, systemic blood pressure did not increase. Renal plasma flow and glomerular filtration rate remained unmodified after NEP inhibition. Filtration fraction (33 +/- 13%), diuresis (196 +/- 62%), and natriuresis (315 +/- 105%) increased significantly in relation to ANP and cGMP. A strong inverse relationship was observed between excreted cGMP and sodium reabsorption (r = -0.71, P < 0.0001). Thus, despite significantly increasing endothelin-1, NEP inhibition did not adversely influence systemic or renal hemodynamics in transplant patients. ANP, possibly through a tubular action, enhances the natriuresis observed after NEP inhibition.     

Vasodilatory and diuretic actions of alpha-human atrial natriuretic polypeptide (alpha-hANP)

Vascular and diuretic actions of synthetic alpha-human atrial natriuretic polypeptide (alpha-hANP) were studied using anesthetized dogs and isolated canine arterial strip preparations. alpha-hANP, when given intra-arterially or intravenously, dilated the renal artery more selectively than the vertebral, femoral, common carotid and coronary arteries. alpha-hANP selectively relaxed the high K+-contracted renal artery strip as compared with the basilar, coronary and femoral arterial strips. Intravenous alpha-hANP also increased urine volume and urinary excretion of electrolytes at doses, at which it increased renal blood flow and lowered systemic blood pressure without changing heart rate. It is concluded that alpha-hANP has a vasodilatory property relatively specific for the renal artery, and that it possesses diuretic, natriuretic, kaliuretic, magnesiuretic, calciuretic and chloruretic activities concomitantly with a definite hypotensive activity.     

Renal effects of administered atrial natriuretic peptide in the conscious, aging rat

Studies were performed in conscious, chronically catheterized male Sprague-Dawley rats to investigate the effect of administered atrial natriuretic peptide (ANP) on blood pressure, renal hemodynamics and urinary electrolyte excretion. Studies were performed on young adult (3-4 month old) rats and on aging rats (18-24 months of age). Low dose ANP (80 ng/kg/min for 60 min) had no effects on renal hemodynamics in either young or old rats and produced only a slight blood pressure reduction in young animals. No effect on urinary electrolyte excretion was evident in young rats whereas in the old animals, low dose ANP produced large rises in the rate of sodium excretion, fractional excretion of sodium and urine flow rate. A four fold higher dose of ANP evoked a moderate natriuretic and a marked antihypertensive response in young rats. Time control studies indicated that time alone had no influence on urinary sodium excretion rate, the fractional excretion of sodium or urine flow rate. These studies indicate a much enhanced sensitivity to the natriuretic effects of administered ANP by the kidneys of old rats.     

Cardiac natriuretic peptides and pancreatic islet blood flow in anesthetized rats.

The aim of the study was to evaluate effects of cardiac natriuretic peptides on splanchnic circulation, especially to the pancreatic islets. Pentobarbital-anesthetized rats were infused intravenously (0.01 ml/min for 20 min) with saline, atrial natriuretic peptide (ANP; 0.25 or 0.5 microg/kg BW/min), brain natriuretic peptide (BNP; 0.5 microg/kg BW/min) or C-type natriuretic peptide (CNP; 0.5 or 2.0 microg/kg BW/min). Splanchnic blood perfusion was then measured with a microsphere technique. Mean arterial blood pressure was decreased by ANP and BNP, but not by CNP. The animals given the highest dose of ANP became markedly hypoglycemic, whilst no such effects were seen in any of the other groups of animals. Total pancreatic blood flow was decreased by the highest dose of CNP, whereas no change was seen after administration of the other peptides. Islet blood flow was increased by the highest dose of ANP. Neither BNP nor CNP affected islet blood flow. None of the natriuretic peptides influenced duodenal, colonic or arterial hepatic blood flow. It is concluded that cardiac natriuretic peptides exert only minor effects on splanchnic blood perfusion in anesthetized rats. However, islet blood perfusion may be influenced by ANP.     

Are prostaglandins involved in atrial natriuretic peptide mechanisms of cardiovascular control?

Atrial natriuretic peptide (ANP) can excite cardiac nerve endings and invoke a decrease in arterial blood pressure and a reduction in renal sympathetic nerve activity. Our laboratory has previously demonstrated that this renal depressor reflex was invoked by systemic injection of ANP and not by the direct application of ANP to the epicardium, a major locus for vagal afferents. We now examine whether inhibition of prostaglandin synthesis impairs reflex responses that are normally associated with ANP injections. Renal sympathetic nerve activity, arterial blood pressure, and heart rate were recorded in anesthetized rats. Indomethacin was used to inhibit prostaglandin synthesis through the cyclooxygenase pathway. The ANP-mediated decrease in arterial blood pressure and renal sympathetic nerve activity, observed when prostaglandin synthesis was inhibited, did not differ significantly from the decreases observed in these parameters when prostaglandin synthesis was not inhibited. Heart rate remained unchanged. Our results suggest that the sympatho-inhibitory effects of ANP do not require prostaglandins as intermediary compounds.     

Age differences in renal response to atrial natriuretic peptide in rabbits

Plasma levels of atrial natriuretic peptide (ANP) and the effect of exogenous ANP on renal function have been studied in newborn and adult rabbits. In order to investigate an age difference in responsiveness to ANP, we studied the renal effects of alpha-human ANP (1-28) administered at the same dose per kg body weight in adult and neonatal rabbits. Plasma basal ANP levels were similar in 18 newborn (4- to 11-day-old) compared to 7 adult rabbits (150 +/- 16 and 151 +/- 28 pg/ml, resp.). Eleven newborn and 11 adult rabbits were anesthetized and mechanically ventilated. After a control period, each animal received an hANP loading dose (3 micrograms/kg i.v.), followed by an infusion of 0.3 micrograms/kg/min. Blood gases remained stable throughout the experiment in both groups. Mean blood pressure decreased in newborn (28.5 +/- 0.8 to 26.2 +/- 1.0 mmHg) and adult (92 +/- 3 to 84 +/- 3 mmHg) animals. Percent hANP-induced changes in renal functions in newborn and adult rabbits were, respectively: urine flow rate: -21 +/- 4% and +57 +/- 8%; urinary sodium excretion: +4 +/- 7% and +81 +/- 11%; glomerular filtration rate (GFR): -19 +/- 4% and -4 +/- 6%; renal blood flow (RBF): -22 +/- 4% and -11 +/- 5%. As expected, diuresis and natriuresis increased in adult rabbits. Failure of hANP to increase natriuresis and diuresis in newborn rabbits could be related to the marked decrease in GFR, receptor immaturity and/or interactions with other hormonal systems.     

The effects of clonidine on the kidney function in the anesthetized dog

Studies were performed to determine the mechanism by which the antihypertensive agent clonidine increased urine flow. The response of the kidney has been examined in four combinations. The parameters of renal function have been compared during volume expansion by 1.5-2.0% body weight Ringer solution. In the control animals, volume expansion by 2% body weight, resulted in a slight increase in sodium excretion and urine flow. In 10 anesthetized dogs 1.0 microgram/kg/min of clonidine infused i.v. during 30 minutes (the total amount of clonidine infused was 30 micrograms/kg) decreased the arterial blood pressure from 136 +/- 13 mmHg to 127 +/- 12 mmHg and elevated urine flow from 2.95 +/- 1.65 ml/min to 4.34 +/- 1.77 ml/min while the urine osmolality diminished from 399 +/- 107 mosm/l to 265 +/- 90 mosm/l and the glomerular filtration remained constant. In 5 animals 0.1 microgram/kg/min of clonidine was infused into the left renal artery (this dose is corresponding to the renal fraction of the cardiac output) without any effects in the left kidney. 1.0 microgram/kg/min of clonidine infused directly into the left renal artery produced vasoconstriction in the ipsilateral kidney, decreased the glomerular filtration rate and the urine flow. By contrast in the right kidney the urine flow rose without hemodynamic changes, and the urine osmolality became hypoosmotic compared to the plasma. In ten dogs 1.0 microgram/kg/min of clonidine and 1 mU/kg/min of arginine-vasopressin were infused intravenously. The vasopressin infusion superimposed on the clonidine could not inhibit the increase of the urine excretion, and the fall of the urine osmolality. The results suggest that the clonidine increases the renal medullary blood flow possibly via a direct mechanism, decreases the sympathetic outflow to the kidney and via an indirect pathway, mediated by the renin-angiotensin system. The renal medullary flow increase produces a washout of the medullary osmotic gradient, and the water reabsorption diminishes.     

Effect of angiotensin converting enzyme inhibition on renal response to atrial natriuretic factor in rats

Previous studies have shown that atrial natriuretic factor (ANF) inhibits renin secretion whereas cilazapril blocks angiotensin II generation via converting enzyme inhibition. Both agents enhance renal excretory function. The present study was conducted to test whether the renin-angiotension system is involved in the ANF-induced renal effects. ANF was administered to anesthetized normal rats (n = 16) with or without a simultaneous infusion of cilazapril. Single bolus injections of ANF at doses of 2.5 micrograms/kg and 5.0 micrograms/kg significantly decreased mean arterial blood pressure by 6.8 +/- 2.3% and 9.4 +/- 2.2%, respectively. The corresponding increases in glomerular filtration rate were 5.6 +/- 3.7% and 8.4 +/- 2.8%, in absolute sodium excretion were 55.0 +/- 18.5% and 105.2 +/- 39.9%, and in urine flow were 24.8 +/- 9.3% and 35.6 +/- 14.6%. Intravenous infusion of cilazapril (33 micrograms/kg.min) reduced the arterial blood pressure, elevated the glomerular filtration rate and increased sodium and water excretion. The corresponding doses of ANF administration during continuous infusion of cilazapril further decreased blood pressure by 8.3 +/- 1.9% and 10.9 +/- 5.4%, respectively. However, there were no significant changes in the glomerular filtration rate and sodium and water excretion. The failure of ANF to exhibit a renal effect was irrelevant to the lowering blood pressure induced by cilazapril. These results suggest that reduced endogenous angiotensin II generation contributes to the renal, but not the hypotensive, effect of ANF.     

Atrial natriuretic peptide administration to normal and salt depleted rats--effects on digoxin-like immunoreactive factor, aldosterone, ACTH, and renal function

In view of the known interrelationships between renin, aldosterone, and atrial natriuretic peptide (ANP), we sought to examine whether there also exists an interaction between ANP and digoxin-like immunoreactive factor (DLIF). We therefore studied the effects of ANP administration on normal and salt-depleted rats, and measured the effects on blood pressure, urine output, glomerular filtration rate, sodium excretion, aldosterone, ACTH, and DLIF levels. ANP administration resulted in a significant elevation of sodium excretion and glomerular filtration rate and a fall in blood pressure. DLIF concentrations in plasma rose significantly, as did urinary DLIF excretion. ANP administration resulted in a fall in aldosterone as well as ACTH. These observations suggest that ANP has a direct inhibitory effect on ACTH secretion. Our findings support the concept of an interrelationship between ANP and DLIF.     

Synthesis and renal function study of Val-Asp-[Arg8]-vasopressin

A new neurohypophyseal hormone analogue, Val-Asp-[Arg⁸]-vasopressin (VAAVP), was synthesized by the stepwise solution techniques and its effect on systemic blood pressure and renal function was examined in nondiuretic Sprague-Dawley rats. Clearance of inulin was used to study glomerular filtration rate. Intravenous administration of 50 pmole/100g. b. wt. VAAVP caused diuresis and increase in urinary excretion of sodium and potassium without significant change of mean arterial blood pressure. The same dose of VAAVP caused a maximal increase infractional excretion of sodium by 80% although it also caused a slight increase of GFR. The present study suggests that VAAVP could be a natriuretic hormone which acts directly on kidney without affecting systemic circulation.     

Lipid peroxidation--an initial event in experimental acute renal failure

A method was developed to monitor the occurrence of lipid peroxidation (LPO) during ischemia and Na-maleate-induced acute renal failure (ARF) on male rats in vivo by measuring malondialdehyde (MDA) levels in arterial and renal venous blood and in urine. No signs of LPO could be detected under control conditions. In ischemic ARF produced by 45 min of renal artery clamping a steep increase of MDA was found in the renal venous effluent immediately after starting reperfusion. This effect was nearly abolished after 5 min of blood reflow while glomerular filtration remained at 5% of control value during a 90-min postischemic observation period. Intoxication with Na-maleate leads to enhanced LPO in combination with an impaired renal function 2 h after administration. These findings would well explain cellular damage and some aspects of renal dysfunction associated with the initiation phase of ARF.     

Dietary sodium,glomerular filtration rate autoregulation,and glomerular size distribution profiles in domestic fowl (Gallus gallus)

Summary Mammalian glomerular filtration rate (GFR) autoregulation can be impaired by protocols that inhibit tubuloglomrular feedback, such as high sodium intake. Domestic fowl were fed diets containing either high sodium (0.39% Na: High-Na Group) or low sodium (0.03% Na: Low-Na Group). An arterial snare was used to reduce renal arterial perfusion pressure (RAPP) in a stepwise fashion to evaluate GFR autoregulation. Absolute sodium excretion, fractional sodium excretion (FE_Na), and ambient systemic arterial blood pressure were significantly elevated in the High-Na Group when compared with the Low-Na Group, and pressure natriuresis was abolished by the Low-Na diet. However, GFR autoregulatory profiles were identical in birds fed High-Na and Low-Na diets, suggesting that tubuloglomerular feed-back does not contribute significantly to avian GFR autoregulation. Filtering glomeruli were stained in vivo with alcian blue dye to determine if RAPP-induced reductions in GFR are associated with cessation of filtration (glomerular intermittency) by a portion of the nephron population. RAPP was held below the GFR autoregulatory range (experimental group) or was at ambient systemic arterial pressure (control group) during glomerular staining. Reducing RAPP below the autoregulatory range reduced GFR by 50%, but similar glomerular size distribution profiles were observed for experimental and control groups. These results indicate that sustained glomerular intermittency does not contribute to the decrease in GFR when RAPP is reduced below the autoregulatory range.Abbreviations BW body weight - C control - E excretion - FE fractional excretion - FF filtration fraction - GFR glomerular filtration rate - PAH p-amino hippuric acid - RAPP renal arterial perfusion pressure - RPF renal plasma flow - RT reptilian-type - SNGFR single nephron glomerular filtration rate - U _OSM urine osmolarity - UFR urine flow rate     

Hemodynamic and renal effects of low-dose brain natriuretic peptide infusion in humans: a randomized,placebo-controlled crossover study

Brain natriuretic peptide (BNP) is a cardiac hormone with natriuretic activity. The aim of this study was to investigate the cardiovascular effects of pathophysiological levels of BNP on central hemodynamics, cardiac function, renal hemodynamics and function, and microvascular hemodynamics in healthy subjects. In this double-blind, placebo-controlled crossover study, we intravenously infused BNP (4 pmol. kg-1. min-1) or placebo for 1 h on two separate days in 12 healthy subjects (mean age, 60 +/- 5 yr). Nailfold and conjunctival capillary density, finger-skin (thermoregulatory) microvascular blood flow, and cardiac output were studied before and after infusion using intravital videomicroscopy, laser-Doppler fluxmetry, and echocardiography, respectively. Furthermore, during infusion, we measured the effective renal plasma flow and glomerular filtration rate using p-aminohippurate and inulin clearances. Blood pressure and heart rate were monitored for all measurements. Compared with placebo, BNP significantly decreased stroke volume with a tendency to decrease cardiac output. With subjects in the sitting position, mean arterial pressure decreased and heart rate increased after BNP infusion, whereas with subjects in the supine position, these variables remained unchanged. BNP increased natriuresis, diuresis, glomerular filtration rate, filtration fraction, and filtered load of Na+ compared with placebo, whereas effective renal plasma flow did not change. BNP did not affect the microvascular capillary density of conjunctiva and skin, microvascular blood flow, total skin oxygen capacity, and postocclusive recruitment. These results suggest that BNP has predominantly central and renal hemodynamic effects; however, it does not influence peripheral microcirculation in skin and conjunctiva.     

C型利钠利尿肽对犬冠脉循环的作用

Ｃ型利钠利尿肽（ＣＮＰ）是新近发现的一种由内皮细胞分泌的利钠利尿肽,本研究采用冠脉内给药方法对比观察了ＣＮＰ、心房利钠尿肽（ＡＮＰ）对犬正常及心肌缺血后冠脉循环的作用,并应用常规离体血管灌流的方法测定了离体冠脉对ＣＮＰ、ＡＮＰ的舒张反应。结果显示：（１）对正常犬,ＣＮＰ、ＡＮＰ均可降低平均动脉压（ＭＡＰ）、远端小冠脉压和大、小冠脉阻力,增加冠脉流量,而不影响心率;（２）心肌缺血后,ＣＮＰ的上述作用依然存在,但ＡＮＰ降低ＭＡＰ的作用基本消失。（３）离体心外膜冠状动脉对ＣＮＰ、ＡＮＰ均呈剂量依赖性舒张反应。结果提示ＣＮＰ、ＡＮＰ均可舒张冠状动脉而改善冠脉循环,并可能对急性心肌缺血的治疗有益