Effects of Bay K 8644 on renal function and renin secretion in anesthetized rats

Our previous study on kidney cortical slices showed that Bay K 8644, a dihydropyridine calcium channel agonist, produced a dose-dependent inhibitory action on the release of renin. The present study was performed to examine the effect of Bay K 8644 on renal function and renin secretion in vivo. When Bay K 8644 was directly infused into the renal artery of anesthetized rats, 2 micrograms/kg/min had no effect on renal blood flow (RBF) and glomerular filtration rate (GFR), but decreased urine flow (UF), urinary sodium excretion (UNaV) and fractional sodium excretion (FENa) by about 30%, 55% and 35%, respectively, thereby suggesting that Bay K 8644 enhanced the tubular reabsorption of water and sodium. When 10 micrograms/kg/min were infused, RBF, GFR, UF, UNaV and FENa decreased to about 95%, 70%, 35%, 35% and 30% of each control value. The administration of Bay K 8644 at 10 micrograms/kg/min did not influence the basal levels of plasma renin activity (PRA) and renin secretion rate (RSR), but did inhibit significantly isoproterenol-induced increasing effects on PRA and RSR. These results indicate that the activation of voltage-dependent calcium channels with Bay K 8644 influences the control of renal function and renin secretion in vivo.     

Effect of parathyroid hormone on renin secretion

The ability of parathyroid hormone (PTH) to increase renin secretion was investigated in pentobarbital-anesthetized dogs. An intravenous infusion of bovine PTH 1-34, at the dose of 0.028 microgram/kg-1 min-1 increased renin secretion by 149% (501 +/- 105 to 1249 +/- 309 ng hr-1 min-1); renin secretion returned to control values during the recovery period. In order to determine whether PTH acted directly on the kidney to increase renin secretion, PTH was infused into the right renal artery at doses of 0.0014 to 0.0028 microgram/kg-1 min-1 and renin secretion from the right kidney was compared to that from the left (control) kidney. Renin secretion from the right (PTH-infused) kidney was not greater than control values for that kidney or different from the renin secretory rate of the left (control) kidney. In contrast, the excretion rates of both phosphate and sodium from the right kidney were greater than control values and from the excretion rates of the left kidney. These data suggest that PTH, while acting directly on the kidney to increase phosphate and sodium excretion, does not elevate renin secretion by a direct renal action.     

Renal and systemic effects of synthetic atrial natriuretic factor

A synthetic peptide corresponding to a sequence of 26 amino acids contained in endogenous rat atrial natriuretic factor (ANF), was infused into one renal artery of anesthetized dogs for a comprehensive in vivo evaluation of the renal and systemic effects of pure ANF. The results proved conclusively that ANF acted directly on the kidney since urine volume and fractional excretion of sodium, potassium, chloride and calcium were elevated in a dose-related manner in the ANF-treated kidney, but were not significantly affected in the contralateral saline-infused organ. The maximum effects achieved with the synthetic ANF were higher than any reported following intravenous administration of crude extracts of rat atria and were similar to those produced by thiazide diuretics. In four of the five dogs studied, renal vascular resistance fell progressively as doses of ANF were increased. Glomerular filtration rate was not significantly elevated during ANF infusion, but was correlated with sodium excretion rates. Even though mean arterial pressure was progressively reduced, there was no significant change in heart rate and no stimulation of renin secretion. Arterial cyclic GMP concentration was higher in the basal state and rose more rapidly than did renal venous levels, indicating that increases in circulating concentrations of arterial cyclic GMP originated from an extrarenal source. Dose-related elevations in urinary cyclic GMP excretion could be explained by increased cyclic GMP filtration, by enhanced production in tubular cells, or by renal tubular secretion. Especially in the saline-infused kidney, there was a clear dissociation between excretion of cyclic GMP and fractional sodium excretion. We conclude that the synthetic ANF increased electrolyte excretion via a direct renal action which was not solely dependent upon changes in renal vasculature, renin secretion or cyclic GMP levels.     

Ca2+ antagonists and db-cAMP sustain a rise in renal blood flow induced by acetylcholine in indomethacin-treated dogs

Renal arterial infusion of acetylcholine (ACh) in the dog normally produces a sustained rise in sodium excretion (UNaV) and in renal plasma flow (RPF). When prostaglandin (PG) synthesis is inhibited, ACh induces only a transient increase in UNaV and RPF followed by a progressive decline in UNaV and RPF, and a rise in renin secretory rate (RSR). Renal arterial infusion of PGE2 but not a vasodilator such as bradykinin restored the response to ACh to normal in indomethacin (Indo)-treated dogs. During renal arterial infusion of dibutyryl cyclic AMP (6 mg/min), ACh also produced a sustained increase in UNaV and RPF despite an inhibition of PG synthesis by Indo. Renal arterial infusion of verapamil (60 micrograms/min) or diltiazem (60 micrograms/min) also prevented the subsequent fall in RPF when ACh was infused; RSR, however, did not show a rise. The results suggest that synthesis of PGE2 with stimulation of cAMP is required for sustained ACh action. When PGE synthesis is inhibited, ACh may produce renal vasoconstriction by increasing intracellular Ca2+ concentration. The partial effect of calcium channel blockers suggests that release of calcium from intracellular stores as well as calcium entry may mediate the response.     

Effects of captopril and enalapril on sodium excretion and blood pressure in sodium-deficient dogs

Inhibition of angiotensin I-converting enzyme (ACE) (kininase II) provides a powerful new method for evaluating the role of the renin-angiotensin-aldosterone and kallikrein-kinin systems in the control of aldosterone secretion, renal function, and arterial blood pressure. This study compares the effects of long-term administration of a sulfhydryl inhibitor, captopril, with a nonsulfhydryl inhibitor, enalapril (1-[N-[1-(ethoxycarbonyl-3-phenylpropyl]-L-alanyl]-L-proline), in conscious sodium-deficient dogs. Plasma aldosterone concentration (PAC), plasma renin activity (PRA), urinary sodium excretion (UNaV), arterial pressure (AP), blood kinins (BK), urinary kinins (UK), and urinary kallikrein activity (UKA) were determined during long-term inhibition of ACE in sodium-deficient dogs. In response to captopril administration (20 mg/(kg . day], PAC decreased from 38.9 +/- 6.7 to 14.3 +/- 2.3 ng/dl, PRA increased from 3.58 +/- 0.53 to 13.7 +/- 1.6 ng/(ml . h), UNaV increased from 0.65 +/- 0.27 to 6.4 +/- 1.2 meq/day, AP decreased from 102 +/- 3 to 65 +/- 2 mm Hg, BK increased from 0.17 +/- 0.02 to 0.41 +/- 0.04 ng/ml, UK increased from 7.2 +/- 1.5 to 31.4 +/- 3.2 micrograms/day, and UKA decreased from 23.6 +/- 3.1 to 5.3 +/- 1.2 EU/day. Quantitatively similar changes in AP, UNaV, and PAC were observed in sodium-deficient dogs in response to long-term enalapril administration (4 mg/(kg X day]. In sodium-deficient dogs maintained on captopril or enalapril for several days, angiotensin II (AngII) infusion (3 ng/(kg X min] restored PAC, UNaV, and AP to levels observed in untreated sodium-deficient dogs. These data indicate that the long-term hypotensive and natriuretic actions of inhibitors of ACE are mediated by inhibition of AngII formation and that the renin-angiotensin system plays an essential role in regulating aldosterone secretion, renal function, and AP during sodium deficiency.     

Effects of substance P on renin release and renal function in anesthetized dogs.

Substance P (SP), a naturally occuring undecapeptide with hypotensive, vasodilatory and smooth muscle stimulating properties, was infused intravenously or intrarenally into anesthetized dogs. Infusions of SP intravenously suppressed renin secretion rate (RSR) from 204±45 to 52±18 ng/min (p < 0.02) at an infusion rate of 0.5 ng/kg/min, and to 50±22 ng/min (p < 0.05) at 5 ng/kg/min. When the concentration of SP was further increased to 50 ng/kg/min, RSR increased to a level above the control value (728±81, p < 0.01). Intrarenal infusion of SP produced similar changes in renin release. At infusion rates of 0.5 ng/kg/min and 5 ng/kg/min, RSR was suppressed from 145±18 to 56±18 ng/min (p < 0.05) and to 26±8 ng/min (p < 0.01) respectively. At 50 ng/kg/min, RSR increased to 251±59 (p > 0.1). Both intravenous and intrarenal administration of the peptide significantly lowered arterial blood pressure at the highest two doses. Intrarenal infusion of SP resulted in a significant dose-related increase in urine volume, sodium and potassium excretion, and renal blood flow. In contrast, intravenous infusions did not alter these parameters. Thus SP suppresses renin release in the presence and in the absence of diuresis, natriuresis, and vasodilation.     

Control of right atrial pressure at constant cardiac output suppresses volume natriuresis in anesthetized rats

The blood volume of anesthetized rats was expanded acutely by 33% with donor blood while a caval snare was gradually tightened so that right atrial pressure (RAP) was prevented from rising (n = 6). In control experiments (n = 5) an aortic snare was used to hold mean arterial blood pressure near the values found in the experimental series. However, RAP was allowed to change freely and increased by 1.6 +/- 0.4 mmHg (1 mmHg = 133.322 Pa) during volume expansion. When the two groups were compared, there were no significant differences between their mean arterial blood pressures (near 110 mmHg) or in their cardiac outputs (near 0.25 mL X min-1 X g body weight-1). There were, however, significant differences between their renal responses to the volume load. When RAP was free to change, the rate of volume excretion (V) increased to 30 +/- 15 (SEM) microL X min-1 X g kidney weight-1 (KW) from its control value of 3.49 +/- 0.31 and the rate of sodium excretion (UNaV) increased to 3.59 +/- 0.20 muequiv X min-1 X g KW-1 from its preinfusion value of 0.42 +/- 0.10. When RAP was not allowed to increase during volume loading, V and UNaV did not change from their respective preinfusion values (2.99 +/- 0.46 microL X min-1 X g KW-1 and 0.35 +/- 0.10 muequiv X min-1 X g KW-1). The results imply that during acute blood volume expansion increased central vascular pressure is a prerequisite for the homeostasis of body water and salt.     

Circulation, kidney function, and volume-regulating hormones during prolonged water immersion in humans.

To investigate whether prolonged water immersion (WI) results in reduction of central blood volume and attenuation of renal fluid and electrolyte excretion, these variables were measured in connection with 12 h of immersion. On separate days, nine healthy males were investigated before, during, and after 12 h of WI to the neck or during appropriate control conditions. Central venous pressure, stroke volume, renal sodium (UNaV) and fluid excretion increased on initiation of WI and thereafter gradually declined but were still elevated compared with control values at the 12th h of WI. Atrial natriuretic peptide (ANP) concentration in plasma initially increased threefold during WI and thereafter declined to preimmersion levels, whereas plasma renin activity, plasma aldosterone, and norepinephrine remained constantly suppressed. It is concluded that, compared with the initial increases, central blood volume (central venous pressure and stroke volume) is reduced during prolonged WI and renal fluid and electrolyte excretion is attenuated. UNaV is still increased at the 12th h of WI, whereas renal water excretion returns to control values within 7 h. The WI-induced changes in ANP, plasma renin activity, plasma aldosterone, and norepinephrine may all contribute to the initial increase in UNaV. The results suggest, however, that the attenuation of UNaV during the later stages of WI is due to the decrease in ANP release.     

Actions of nicotine on renal function in dogs

Renal excretory and circulatory responses to nicotine were investigated in anesthetized dogs under three sets of conditions: (a) infusion of nicotine into the left renal artery (ia) at a dose of 0.5 microgram X min-1 X kg body wt-1 X 15 min; (b) ia nicotine after 1.0 mg/kg ia propranolol; and (c) ia nicotine after bilateral adrenalectomy. Measured and calculated left and right renal excretory variables included sodium, potassium, and chloride excretion rates (UNaV, UKV, and UClV, respectively), total solute excretion (UOsV), glomerular filtration rate (GFR), fractional sodium excretion (FENa), and urine flow rate. Systemic arterial pressure and left renal artery blood flow (RBF) were also measured. In seven intact dogs administered nicotine alone, there were significant increases in UNaV, UClV, UOsV, GFR, and urine flow rates from both kidneys. However, nicotine did not significantly affect UKV, FENa, arterial pressure, or RBF. The lack of circulatory effects of nicotine was also observed after either propranolol or adrenalectomy. However, when nicotine was administered after propranolol, the drug evoked significant decreases in UOsV, UNaV, UClV, and GFR, compared with prenicotine values. When nicotine was administered after bilateral adrenalectomy, the drug evoked decreases in the excretory parameters similar to those observed after propranolol. These findings seem to support several inferences: (a) nicotine stimulates renal excretory functions-the alkaloid is saluretic and diuretic; (b) the action of nicotine on the kidney is mediated mainly by the release of catecholamines from the adrenal medulla; (c) catecholamines released by nicotine act mainly on beta-adrenergic receptors; and (d) the saluresis prompted by the release of catecholamines in response to nicotine is due to a subsequent increase in GFR.     

Effect of captopril on renal vascular resistance, renin, prostaglandins and kinin in the isolated perfused kidney

Vasodilatory and natriuretic effects of captopril were studied in the isolated hog kidney perfused with modified Krebs-Ringer solution. Renal arterial infusion of captopril caused increases in releases of renin, prostaglandins (PGE2, 6-keto-PGF1 alpha and PGF2 alpha) and kinin, and was accompanied by a decrease in the renal vascular resistance and an increase in urinary sodium excretion. Indomethacin administered with captopril diminished the saluretic effect of captopril and evoked an increase in kinin, but was associated with a marked decrease in prostaglandin and renin releases, while renal vascular resistance remained decreased. Indomethacin alone did not alter vascular resistance and kinin; however, renin and prostaglandin releases were decreased. Aprotinin administered with captopril showed a decrease in releases of prostaglandins, renin and kinin without any change in vascular resistance. These results suggest that increased release of kinin induced by captopril contributes to a reduction in renal vascular resistance. Increased prostaglandin release after captopril administration may be caused by an increase in kinin without direct involvement of captopril in prostaglandin synthesis. Renal prostaglandins may enhance sodium excretion and mediate renin secretion in captopril perfusion.     

Effects of brain renin-angiotensin on cardiovascular function and saline intake in awake dogs

Initial studies were undertaken to investigate the effects of prolonged administration of angiotensin II (AII), 1 micrograms twice daily, via the lateral ventricles to mongrel dogs on arterial blood pressure and to determine if sodium intake was essential for the development of hypertension. Increasing AII levels in the cerebrospinal fluid for a prolonged period of time produced a sustained hypertensive state only in those dogs in which the daily intake of sodium was increased. The hypertension appeared to be due to an increase in total peripheral resistance. Central administration of AII increased both fluid intake and urine output. In order to assess the hemodynamic effects of increasing endogenous brain AII, renin was injected in doses of 0.025, 0.05, 0.1 and 0.3 units (from porcine kidney) into the lateral ventricles of chronically instrumented awake dogs. Hemodynamic variables were recorded prior to and one and 2 h after the central administration of renin. Renin produced a dose-dependent increase in mean arterial pressure with no significant change in heart rate or carotid, coronary and renal blood flow velocities. Chronic intraventricular administration of renin, 0.15 units twice daily to awake instrumented dogs receiving saline as the drinking fluid, markedly increased the daily intake of saline and increased diastolic and systolic blood pressure without increasing heart rate or carotid, coronary or renal blood flow velocities. There appears to be a direct significant relationship between the increase in mean blood pressure due to the intraventricular administration of renin and the volume of saline consumed.     

Distinct roles for renal particulate and soluble guanylyl cyclases in preserving renal function in experimental acute heart failure

Worsening renal function in the setting of human acute heart failure (AHF) predicts poor outcomes, such as rehospitalization and increased mortality. Understanding potential renoprotective mechanisms is warranted. The guanylate cyclase (GC) enzymes and their second messenger cGMP are the target of two important circulating neurohumoral systems with renoprotective properties. Specifically, natriuretic peptides (NP) released from the heart with AHF target particulate GC in the kidney, while the nitric oxide (NO) system is an activator of renal soluble GC. We hypothesized that both systems are essential to preserve renal excretory and hemodynamic function in AHF but with distinct roles. We investigated these roles in three groups of anesthetized dogs (6 each) with AHF induced by rapid ventricular pacing. After a baseline AHF clearance, each group received intrarenal vehicle (control), N(G)-monomethyl-l-arginine (l-NMMA), a competitive NO inhibitor (50 microg.kg(-1).min(-1)) or a specific NP receptor antagonist, HS-142-1 (0.5 mg/kg). We observed that intrarenal l-NMMA decreased renal blood flow (RBF) without significant decreases in glomerular filtration rate (GFR), urinary sodium excretion (UNaV), or urinary cGMP. In contrast, HS-142-1 resulted in a decrease in UNaV and cGMP excretion together with a reduction in GFR and an increase in distal fractional tubular sodium reabsorption. We conclude that in AHF, the NP system plays a role in maintaining sodium excretion and GFR, while the function of NO is in the maintenance of RBF. These studies have both physiological and therapeutic implications warranting further research into cardiorenal interactions in this syndrome of AHF.     

Participation of substance P in the control of renin release.

The effect of the hypothalamic undecapeptide substance P on renin secretion rate was studied in the denervated dog kidney. Intrarenal infusion of substance P at a rate of 0.2 ng/kg/min suppressed renin secretion rates from 258.5 ± 28.5 ng/min to 133.1 ± 23.2 ng/min (p<0.001). Substance P infused at this dose neither changed blood pressure nor did it affect renal cortical plasma flow, glomerular filtration rate or sodium excretion. Thus, the suppression of renin release by substance P cannot be explained by any of the known control mechanisms. It is proposed that substance P participates in the control of renin release by a direct effect on the juxtaglomerular cells.     

Is there a role for renal alpha 2-adrenoceptors in the pathogenesis of hypertension?

Current information suggests that alpha 2-adrenoceptors do not directly influence vascular resistance or Na reabsorption in the rat kidney. To reexamine the effects of alpha 2-agonists we used isolated rat kidneys perfused at 37.5 degrees C with precise measurement of renal artery pressure and flow. The recirculating perfusate contained pyruvate as the sole metabolic substrate which enabled us to use gluconeogenesis as an index of proximal tubular alpha 1-responses. Clonidine and guanfacine in 100 nM concentrations decreased phosphate excretion without altering Na, Cl, or K reabsorption or gluconeogenesis; 500 nM concentrations increased vascular resistance and decreased glomerular filtration rate and Na, Cl, and K excretion with no significant effect on gluconeogenesis. Prior thyroparathyroidectomy prevented the antiphosphaturic but not the antinatriuretic or vascular responses. Clonidine, an alpha 2-agonist with some alpha 1-activity, was a more potent vasoconstrictor than methoxamine or guanfacine. In the presence of prazosin (1 microM), norepinephrine (60 nM) stimulated phosphate reabsorption; norepinephrine alone did not stimulate phosphate reabsorption which indicates alpha 1-antagonism of this alpha 2-response to NE. These results and a literature review suggest that increased renal alpha 2-adrenoceptors could raise renal vascular resistance, reduce renin secretion, and antagonize parathyroid hormone effects on Pi, Ca, HCO3, and Na reabsorption to produce a low renin type of hypertension with increased proximal Na reabsorption and abnormal Ca and Pi excretion.     

Nitric oxide synthase and cGMP-mediated stimulation of renin secretion

The interaction between nitric oxide (NO) and renin is controversial. cAMP is a stimulating messenger for renin, which is degraded by phosphodiesterase (PDE)-3. PDE-3 is inhibited by cGMP, whereas PDE-5 degrades cGMP. We hypothesized that if endogenous cGMP was increased by inhibiting PDE-5, it could inhibit PDE-3, increasing endogenous cAMP, and thereby stimulate renin. We used the selective PDE-5 inhibitor zaprinast at 20 mg/kg body wt ip, which we determined would not change blood pressure (BP) or renal blood flow (RBF). In thiobutabarbital (Inactin)-anesthetized rats, renin secretion rate (RSR) was determined before and 75 min after administration of zaprinast or vehicle. Zaprinast increased cGMP excretion from 12.75 +/- 1.57 to 18.67 +/- 1.87 pmol/min (P < 0.003), whereas vehicle had no effect. Zaprinast increased RSR sixfold (from 2.95 +/- 1.74 to 17.62 +/- 5.46 ng ANG I. h(-1) x min(-1), P < 0.024), while vehicle had no effect (from 4.08 +/- 2.02 to 3.87 +/- 1.53 ng ANG I x h(-1) x min(-1)). There were no changes in BP or RBF. We then tested whether the increase in cGMP could be partially due to the activity of the neuronal isoform of NO synthase (nNOS). Pretreatment with the nNOS inhibitor 7-nitroindazole (7-NI; 50 mg/kg body wt) did not change BP or RBF but attenuated the renin-stimulating effect of zaprinast by 40% compared with vehicle. In 7-NI-treated animals, zaprinast-stimulated cGMP excretion was attenuated by 48%, from 9.17 +/- 1.85 to 13.60 +/- 2.15 pmol/min, compared with an increase from 10.94 +/- 1.90 to 26.38 +/- 3.61 pmol/min with zaprinast without 7-NI (P < 0.04). This suggests that changes in endogenous cGMP production at levels not associated with renal hemodynamic changes are involved in a renin-stimulatory pathway. One source of this cGMP may be nNOS generation of NO in the kidney.     

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.     

Renin release from nonclipped kidneys of 2K-1C hypertensive rats

This study examined renin release and renal function of the nonclipped kidney of 2K-1C rats (HYPER) with hypertension of 3 to 4 weeks duration. Kidneys from uninephrectomized rats (UN) served as controls. The kidneys were removed and perfused in vitro and renin release was compared under basal conditions and then under stimulated conditions using (a) a 50 mm Hg reduction in perfusion pressure (LP), (b) beta-receptor stimulation with isoproterenol (ISOP), or (c) perfusion with a low calcium solution (LCa). Basal perfusate flow, glomerular filtration rate, urine flow, sodium excretion, and basal renin release were all lower in HYPER kidneys than UN kidneys. UN kidneys showed striking increases in renin release with all three stimuli employed. HYPER kidneys showed a significant but attenuated response to ISOP and showed no detectable response to LP or LCa. Renin content of HYPER kidneys was found to be 28% of the renin content of UN kidneys. The results show that chronic hypertension leads to increased renal vascular resistance, reduced glomerular filtration, and reduced solute excretion in the nonclipped kidney. The results suggest that a reduction in renin content plays a major role in the reduced rates of basal renin release and the attenuated renin responses to a number of stimuli observed in this experimental model.     

Renal actions of atrial natriuretic peptide on the postischemic kidney

The objective of this study was to evaluate the renal actions of atrial natriuretic peptide (ANP) in the unilateral postischemic kidney of anesthetized dogs with a severe reduction in glomerular filtration rate. The dose of atrial natriuretic peptide (50 ng.kg-1.min-1) we gave did not alter the mean systemic arterial pressure, renal blood flow, and glomerular filtration rate in the normal kidney, as determined in foregoing studies. ANP was infused into the intrarenal artery continuously for 60 min after the release from 45 min of complete renal artery occlusion. In the vehicle-infused group, the glomerular filtration rate fell dramatically (6% of control), the renal blood flow decreased (60% of control), and the mean systemic arterial pressure tended to increase (136% of control). The urine flow rate and urinary excretion of sodium decreased significantly (25 and 25%, respectively) at 30 min after reflow in the postischemic period. Continuous renal artery infusion of ANP resulted in a marked increase in urine flow rate (246% of control) and the urinary excretion of sodium (286% of control). The administration of ANP led to an improvement in renal blood flow (99% of control) and glomerular filtration rate (40% of control), and attenuated the rise in mean systemic arterial pressure (109% of control), compared with findings in the vehicle-infused group. Plasma renin activity and prostaglandin E2 concentration in the renal venous blood were elevated after the release from complete renal artery occlusion in both groups. These results indicate that the vascular effects of ANP on the postischemic kidney were enhanced and that the peptide maintained the natriuretic effect.     

The effects of cardiac denervation on renal function.

Assessment of certain parameters of renal function were carried out before and 1 wk after total denervation of the heart by a method which leaves nerves to other organs intact. No changes in mean blood pressure, central venous pressure, cardiac output, GFR, or RPF were noted after cardiac denervation. UNaV after a low sodium diet was similar during a control period before and after denervation, but in response to expansion of the plasma volume a 3-fold greater natriuresis was seen in the denervated group. Alterations in the filtered load of sodium, the secretion of aldosterone, or most of the recently described physical and compositional factors known to influence sodium excretion cannot adequately explain this natriuresis. Expansion of an already augmented plasma volume after denervation or the possibility of a natriuretic or antinatriuretic factor with afferents interrupted in the process of cardiac denervation must be considered as etiologic factors.     

Renal blood flow, early distal sodium, and plasma renin concentrations during osmotic diuresis

Inconsistencies in previous reports regarding changes in early distal NaCl concentration (ED(NaCl)) and renin secretion during osmotic diuresis motivated our reinvestigation. After intravenous infusion of 10% mannitol, ED(NaCl) fell from 42.6 to 34.2 mM. Proximal tubular pressure increased by 12.6 mmHg. Urine flow increased 10-fold, and sodium excretion increased by 177%. Plasma renin concentration (PRC) increased by 58%. Renal blood flow and glomerular filtration rate decreased, however end-proximal flow remained unchanged. After a similar volume of hypotonic glucose (152 mM), ED(NaCl) increased by 3.6 mM, (P < 0.01) without changes in renal hemodynamics, urine flow, sodium excretion rate, or PRC. Infusion of 300 micromol NaCl in a smaller volume caused ED(NaCl) to increase by 6.4 mM without significant changes in PRC. Urine flow and sodium excretion increased significantly. There was a significant inverse relationship between superficial nephron ED(NaCl) and PRC. We conclude that ED(Na) decreases during osmotic diuresis, suggesting that the increase in PRC was mediated by the macula densa. The results suggest that the natriuresis during osmotic diuresis is a result of impaired sodium reabsorption in distal tubules and collecting ducts.