Sodium Excretion and Renin Secretion after Continuous Versus Pulsatile Infusion of Oxytocin in Rats*

Saline administration may change renin-angiotensin-aldosterone system (RAAS) activity and sodium excretion at constant mean arterial pressure (MAP). We hypothesized that such responses are elicited mainly by renal sympathetic nerve activity by β1-receptors (β1-RSNA), and tested the hypothesis by studying RAAS and renal excretion during slow saline loading at constant plasma sodium concentration (Na+ loading; 12 μmol Na+·kg−1·min−1 for 4 h). Normal subjects were studied on low-sodium intake with and without β1-adrenergic blockade by metoprolol. Metoprolol per se reduced RAAS activity as expected. Na+ loading decreased plasma renin concentration (PRC) by one-third, plasma ANG II by one-half, and plasma aldosterone by two-thirds (all P < 0.05); surprisingly, these changes were found without, as well as during, acute metoprolol administration. Concomitantly, sodium excretion increased indistinguishably with and without metoprolol (16 ± 2 to 71 ± 14 μmol/min; 13 ± 2 to 55 ± 13 μmol/min, respectively). Na+ loading did not increase plasma atrial natriuretic peptide, glomerular filtration rate (GFR by 51Cr-EDTA), MAP, or cardiac output (CO by impedance cardiography), but increased central venous pressure (CVP) by ∼2.0 mmHg ( P < 0.05). During Na+ loading, sodium excretion increased with CVP at an average slope of 7 μmol·min−1·mmHg−1. Concomitantly, plasma vasopressin decreased by 30–40% ( P < 0.05). In conclusion, β1-adrenoceptor blockade affects neither the acute saline-mediated deactivation of RAAS nor the associated natriuretic response, and the RAAS response to modest saline loading seems independent of changes in MAP, CO, GFR, β1-mediated effects of norepinephrine, and ANP. Unexpectedly, the results do not allow assessment of the relative importance of RAAS-dependent and -independent regulation of renal sodium excretion. The results are compatible with the notion that at constant arterial pressure, a volume receptor elicited reduction in RSNA via receptors other than β1-adrenoceptors, decreases renal tubular sodium reabsorption proximal to the macula densa leading to increased NaCl concentration at the macula densa, and subsequent inhibition of renin secretion.

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Interaction of renal beta 1-adrenoceptors and prostaglandins in reflex renin release

AJP Renal Physiology ◽

10.1152/ajprenal.1983.244.4.f418 ◽

1983 ◽

Vol 244 (4) ◽

pp. F418-F424 ◽

Cited By ~ 3

Author(s):

U. Kopp ◽

G. F. DiBona

Keyword(s):

Sodium Excretion ◽

Perfusion Pressure ◽

Carotid Sinus ◽

Urinary Sodium Excretion ◽

Renal Perfusion ◽

Prostaglandin Synthesis ◽

Urinary Sodium ◽

Secretion Rate ◽

Renin Secretion ◽

Renal Perfusion Pressure

Anesthetized dogs with isolated carotid sinus preparation were used to examine the mechanisms involved in the increase in renin secretion rate produced by carotid baroreceptor reflex renal nerve stimulation (RNS) at constant renal perfusion pressure. Lowering carotid sinus pressure by 41 +/- 5 mmHg for 10 min increased mean arterial pressure and heart rate, caused no or minimal renal hemodynamic changes, decreased urinary sodium excretion, and increased renin secretion rate. Metoprolol, a beta 1-adrenoceptor antagonist, given in the renal artery, did not affect the decrease in urinary sodium excretion but attenuated the increase in renin secretion rate, from 1,764 +/- 525 to 412 +/- 126 ng/min (70 +/- 8%). Indomethacin or meclofenamate, prostaglandin synthesis inhibitors, did not affect the decrease in urinary sodium excretion but attenuated the increase in renin secretion rate, from 1,523 +/- 416 to 866 +/- 413 ng/min (51 +/- 18%). Addition of metoprolol to indomethacin-pretreated dogs attenuated the increase in renin secretion rate from 833 +/- 327 to 94 +/- 60 ng/min (86 +/- 10%). These results indicate that reflex RNS at constant renal perfusion pressure results in an increase in renin secretion rate that is largely mediated by renal beta 1-adrenoceptors and is partly dependent on intact renal prostaglandin synthesis. The beta 1-adrenoceptor-mediated increase in renin secretion rate is independent of and not in series with renal prostaglandins.

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Control of renin secretion in the anesthetized dog

American Journal of Physiology-Legacy Content ◽

10.1152/ajplegacy.1964.207.3.537 ◽

1964 ◽

Vol 207 (3) ◽

pp. 537-546 ◽

Cited By ~ 231

Author(s):

Arthur J. Vander ◽

Richard Miller

Keyword(s):

Blood Pressure ◽

Arterial Blood Pressure ◽

Sodium Excretion ◽

Blood Pressure Reduction ◽

Renin Secretion ◽

Aortic Clamping ◽

Arterial Blood ◽

Pressor Activity ◽

Intrarenal Pressure ◽

Venous Plasma

Renin concentrations of renal venous plasma were indirectly measured by bio-assaying the pressor activity produced by plasma incubation under standardized conditions. Pressor activity was detectable in 85% of control dogs, was reciprocally related to sodium excretion, but did not correlate with arterial blood pressure. Reduction of mean renal arterial pressure to 90 mm Hg by an aortic clamp decreased sodium excretion and produced sustained increases in renin secretion and arterial blood pressure proximal to the clamp. Release of the aortic clamp resulted in gradual return of these variables toward control values. Induction of diuresis (osmotic diuretics, chlorothiazide, or acetazolamide) prior to aortic clamping minimized or completely prevented the usual clamp-induced rises in renin secretion and proximal blood pressure. Induction of diuresis during aortic clamping returned the elevated renin secretion and proximal blood pressure toward control values. These effects of diuretics could not be explained by changes in renal hemodynamics or plasma composition. Elevation of ureteral pressure in nondiuretic dogs also increased renin secretion and arterial blood pressure. We conclude that renin secretion is not controlled by blood pressure, per se, or intrarenal pressure, but by the flow or composition of intratubular fluid, probably at the level of the macula densa.

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The Relationship between Sodium Excretion and Renin Secretion by the Perfused Kidney

Experimental Biology and Medicine ◽

10.3181/00379727-150-39115 ◽

1975 ◽

Vol 150 (3) ◽

pp. 728-734 ◽

Cited By ~ 5

Author(s):

M. H. Humphreys ◽

I. A. Reid ◽

R. C. Ufferman ◽

R. A. Lieberman ◽

L. E. Earley

Keyword(s):

Sodium Excretion ◽

Renin Secretion ◽

The Relationship ◽

Perfused Kidney

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Interaction between neural and nonneural mechanisms controlling renin secretion rate

AJP Renal Physiology ◽

10.1152/ajprenal.1984.246.5.f620 ◽

1984 ◽

Vol 246 (5) ◽

pp. F620-F626 ◽

Cited By ~ 7

Author(s):

U. C. Kopp ◽

G. F. DiBona

Keyword(s):

Blood Flow ◽

Arterial Pressure ◽

Sodium Excretion ◽

Urinary Sodium Excretion ◽

Neural Mechanisms ◽

Secretion Rate ◽

The Other ◽

Renin Secretion ◽

Renal Nerves ◽

The Right

The interaction between the neural and nonneural mechanisms in the control of renin secretion rate was studied in anesthetized vagotomized dogs at renal arterial pressures of 170, 130, 90, and 50 mmHg. Left renal nerves were stimulated (RNS) at either 0.075, 0.3, or 0.7 Hz and the right kidney was denervated. At spontaneous renal arterial pressure RNS at 0.075, 0.3, and 0.7 Hz decreased renal blood flow 0, 1 +/- 0, and 2 +/- 1%, respectively, and urinary sodium excretion 0, 2 +/- 1, and 22 +/- 3%, respectively. RNS at 0.075 Hz augmented renin secretion rate at 50 mmHg by 1,806 +/- 505 ng/min; there was no augmentation at 90, 130, and 170 mmHg. RNS at 0.3 Hz augmented renin secretion rate at 50 and 90 mmHg by 2,635 +/- 824 and 1,197 +/- 289 ng/min, respectively; there was no augmentation at 130 and 170 mmHg. RNS at 0.7 Hz augmented renin secretion rate at 50, 90, and 130 mmHg by 1,421 +/- 287, 747 +/- 172, and 273 +/- 163 ng/min, respectively; there was no augmentation at 170 mmHg. RNS at 0.075 Hz to one kidney and 0.7 Hz to the other kidney in the same dog demonstrated that the renin secretion rate was greater with RNS at 0.7 Hz than with 0.075 Hz at 50 and 90 mmHg but not at 130 and 170 mmHg. We conclude that the nonneural and neural mechanisms interact in the control of renin secretion rate. The degree of interaction depends on the level of renal arterial pressure and the intensity of RNS.

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Interrelationship between Acetylcholine and Prostaglandins in the Control of Sodium Excretion and Renin Secretion in Anesthetized dogs. I

Nephron ◽

10.1159/000181644 ◽

1979 ◽

Vol 23 (5) ◽

pp. 247-254 ◽

Cited By ~ 3

Author(s):

John C.H. Yun ◽

Frederic C. Bartter ◽

Gerald D. Kelly ◽

Peter Ramwell

Keyword(s):

Sodium Excretion ◽

Renin Secretion ◽

Anesthetized Dogs

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Renal Na+-K+-ATPase in renin release

AJP Renal Physiology ◽

10.1152/ajprenal.1982.243.6.f598 ◽

1982 ◽

Vol 243 (6) ◽

pp. F598-F603

Author(s):

M. A. Cruz-Soto ◽

J. E. Benabe ◽

J. M. Lopez-Novoa ◽

M. Martinez-Maldonado

Keyword(s):

Sodium Excretion ◽

Filtration Rate ◽

Urine Flow ◽

Renin Secretion ◽

Juxtaglomerular Cells ◽

Secretory Rate ◽

Level Of Activity ◽

Anesthetized Dogs ◽

Natriuretic Effect

The effects of ouabain and furosemide on renin secretion, renal function, and renal Na+-K+-ATPase were investigated in anesthetized dogs. Furosemide (2 mg/kg) induced significant diuresis, natriuresis, an increase in renal blood flow (RBF), and a fivefold increase in renin secretory rate (RSR), but no changes in glomerular filtration rate (GFR). Infusion of ouabain (1 microgram . kg-1 . min-1) into one renal artery during furosemide diuresis increased fractional sodium excretion from 22 +/- 2 to 30 +/- 3% from the ipsilateral kidney but did not change urine flow, RBF, or GFR, whereas RSR fell to control values (698 +/- 203 to 137 +/- 43). When ouabain preceded furosemide, the rise in RBF and RSR induced by furosemide was abolished but sodium excretion increased. Ouabain infused in vivo inhibited Na+-K+-ATPase in microsomal fractions from cortex (34%) and medulla (27%) as compared with control. Neither saline nor furosemide exerted any effect on Na+-K+-ATPase. Moreover, the effect of ouabain alone on Na+-K+-ATPase was not different from that of ouabain plus furosemide. No changes in Mg2+-ATPase were detected in any of the experiments. These results indicate that inhibition of renal Na+-K+-ATPase abolishes furosemide-induced renin secretion despite potentiation of the natriuretic effect of the diuretic. It is apparent that the level of activity of Na+-K+-ATPase is of prime importance for renin secretion. In addition, ouabain may act directly on the juxtaglomerular cells to inhibit renin secretion.

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Normotensive sodium loading in conscious dogs: regulation of renin secretion during β-receptor blockade

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.90753.2008 ◽

2009 ◽

Vol 296 (2) ◽

pp. R428-R435 ◽

Cited By ~ 16

Author(s):

Peter Bie ◽

Simon Mølstrøm ◽

Søren Wamberg

Keyword(s):

Sodium Excretion ◽

Renin Secretion ◽

Conscious Dogs ◽

Renal Nerves ◽

Receptor Blockade ◽

Juxtaglomerular Cells ◽

Ang Ii ◽

Low Sodium Diet ◽

Low Sodium ◽

Per Se

Renin secretion is regulated in part by renal nerves operating through β1-receptors of the renal juxtaglomerular cells. Slow sodium loading may decrease plasma renin concentration (PRC) and cause natriuresis at constant mean arterial blood pressure (MAP) and glomerular filtration rate (GFR). We hypothesized that in this setting, renin secretion and renin-dependent sodium excretion are controlled by via the renal nerves and therefore are eliminated or reduced by blocking the action of norepinephrine on the juxtaglomerular cells with the β1-receptor antagonist metoprolol. This was tested in conscious dogs by infusion of NaCl (20 μmol·kg−1·min−1 for 180 min, NaLoad) during regular or low-sodium diet (0.03 mmol·kg−1·day−1, LowNa) with and without metoprolol (2 mg/kg plus 0.9 mg·kg−1·h−1). Vasopressin V2 receptors were blocked by Otsuka compound OPC31260 to facilitate clearance measurements. Body fluid volume was maintained by servocontrolled fluid infusion. Metoprolol per se did not affect MAP, heart rate, or sodium excretion significantly, but reduced PRC and ANG II by 30–40%, increased plasma atrial natriuretic peptide (ANP), and tripled potassium excretion. LowNa per se increased PRC (+53%), ANG II (+93%), and aldosterone (+660%), and shifted the vasopressin function curve to the left. NaLoad elevated plasma [Na+] by 4.5% and vasopressin by threefold, but MAP and plasma ANP remained unchanged. NaLoad decreased PRC by ∼30%, ANG II by ∼40%, and aldosterone by ∼60%, regardless of diet and metoprolol. The natriuretic response to NaLoad was augmented during metoprolol regardless of diet. In conclusion, PRC depended on dietary sodium and β1-adrenergic control as expected; however, the acute sodium-driven decrease in PRC at constant MAP and GFR was unaffected by β1-receptor blockade demonstrating that renin may be regulated without changes in MAP, GFR, or β1-mediated effects of norepinephrine. Low-sodium diet augments vasopressin secretion, whereas ANP secretion is reduced.

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Role of the Renal Nerves in Modulating Renin Release During Pressure Reduction at the Feline Kidney

Clinical Science ◽

10.1042/cs0690185 ◽

1985 ◽

Vol 69 (2) ◽

pp. 185-195 ◽

Cited By ~ 15

Author(s):

Edward J. Johns

Keyword(s):

Blood Flow ◽

Renal Blood Flow ◽

Sodium Excretion ◽

Filtration Rate ◽

Perfusion Pressure ◽

Renal Perfusion ◽

Renin Secretion ◽

Renal Nerves ◽

Pressure Reduction ◽

Renal Perfusion Pressure

1. Experiments were undertaken in pentobarbitone-anaesthetized cats to determine how reflex activation of the renal nerves altered the responsiveness of the kidney to release renin during reductions in renal perfusion pressure. Reflex activation of the renal nerves was achieved by reducing carotid sinus perfusion pressure by 30 mmHg, which increased systemic blood pressure. During this period renal perfusion pressure was regulated at control levels and neither renal blood flow nor glomerular filtration rate changed, but there was a significant decrease in sodium excretion and increase in renin secretion. Renal denervation abolished both these latter responses. 2. Renal perfusion pressure reduction, by 25-30 mmHg, had no effect on renal blood flow or glomerular filtration rate but significantly decreased sodium excretion and increased renin secretion. Simultaneous reduction of carotid sinus and renal perfusion pressures had no effect on renal blood flow or glomerular filtration rate, decreased sodium excretion, and the magnitude of the increase in renin secretion was significantly greater than that obtained with reduction in renal perfusion pressure alone. Renal denervation abolished the increase in renin secretion during these manoeuvres. 3. During atenolol administration, renal haemodynamics and sodium excretion responses to renal pressure reduction were similar to those obtained in the absence of the drug. Renin secretion was increased, but significantly less than in the absence of atenolol. Simultaneous carotid sinus and renal pressure reductions during atenolol administration had no effect on renal haemodynamics, reduced sodium excretion and increased renin secretion, the magnitude of which was significantly greater than that recorded with only renal pressure reduction in the presence of atenolol. 4. Direct electrical stimulation of the renal nerves, at frequencies which caused a 5-10% reduction in renal blood flow, did not change glomerular filtration rate, decreased sodium excretion by 30% and increased the rate of renin secretion twofold. In the presence of atenolol, such renal nerve stimulation reduced renal blood flow to the same degree, did not change filtration rate, decreased sodium excretion by 37% but did not change renin secretion. 5. These results show that the magnitude of the release of renin in response to renal pressure reduction is dependent on activity within the renal nerves, being blunted after denervation, and enhanced during reflex activation of the renal nerves.

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Role of renal alpha-adrenoceptors mediating renin secretion

AJP Renal Physiology ◽

10.1152/ajprenal.1982.242.6.f620 ◽

1982 ◽

Vol 242 (6) ◽

pp. F620-F626 ◽

Cited By ~ 2

Author(s):

J. L. Osborn ◽

G. F. DiBona ◽

M. D. Thames

Keyword(s):

Blood Flow ◽

Renal Blood Flow ◽

Sodium Excretion ◽

Urinary Sodium Excretion ◽

Urinary Sodium ◽

Renin Secretion ◽

Renal Nerve ◽

Alpha Adrenoceptors ◽

Alpha Adrenoceptor

The increase in renin secretion resulting from low-frequency renal nerve stimulation (0.5 Hz) occurs in the absence of changes in urinary sodium excretion or renal blood flow and is apparently derived from a direct effect of renal sympathetic nerves on juxtaglomerular granular cells. We sought to determine the role of renal alpha-adrenoceptors in this neurally evoked renin secretion. The neurally evoked renin secretion was unaffected by renal alpha-adrenoceptor blockade with phentolamine or prazosin; however, two dose levels of phenoxybenzamine equally inhibited the renin secretion. The renal vasoconstrictor response to graded renal nerve stimulation was similarly diminished by phentolamine, prazosin, and the higher phenoxybenzamine dose, whereas the lower phenoxybenzamine dose was significantly less effective. Renal alpha-adrenoceptor stimulation with methoxamine infusion at doses that were just subthreshold for altering renal blood flow and urinary sodium excretion or at doses that just reduced urinary sodium excretion also did not change renin secretion. Higher doses of methoxamine that decreased both renal blood flow and sodium excretion increased renin secretion. Based on the inability of phentolamine and prazosin to prevent neurally mediated renin secretion and on the dose-response relationship between methoxamine and changes in renin secretion, renal blood flow, and urinary sodium excretion, we conclude that renal alpha-adrenoceptors do not mediate renin secretion elicited by direct neural activation of the juxtaglomerular granular cells. The data suggest that phenoxybenzamine inhibits neurally mediated renin secretion by a mechanism other than renal alpha-adrenoceptor blockade.

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