Renin Secretion Rate Research Articles

Serotonin-induced renin release in the dog kidney

The effect of serotonin (5-HT) on renin release was examined in denervated kidney of the pentobarbital-anesthetized dog. The intraternal arterial infusion of a large dose of 5-HT (1 μg/kg per min) increased the renin secretion rate with an initial decrease and a subsequent increase in renal blood flow. Systemic blood pressure or heart rate was unaffected. The renin release induced by 5-HT was suppressed during intrarernal arterial infusion of a 5-HT 1 and 5-HT 2 antagonist, methysergide (30 μg/kg per min), or a selective 5-HT 2 antagonist, ketanserin (3 μg/kg per min). A cyclooxygenase inhibitor, indomethacin (5 mg/kg i.v.), also suppressed the 5-HT-induced renin release. These results suggest that stimulation of renal 5-HT receptors, probably of the 5-HT 2 type, can induce renin release from the dog kidney, which may be dependent on renal prostaglandin production. The present results, however, do not allow us to conclude that the renal 5-HT receptors play a physiological role in the control of renin release.

Calcium-dependent inhibition of renin secretion: TMB-8 is a non-specific antagonist

Intracellular Ca (Ca i) is an inhibitory second messenger in renin secretion, and it has been hypothesized that some first messengers--especially angiotensin II [A-II] and antidiuretic hormone [ADH], and possibly A 1-adenosine receptor antagonists as well--increase Ca 1 and thereby inhibit renin secretion by causing the release or mobilization of Ca from intracellular sites of sequestration. The present experiments were designed to test this hypothesis, by using 3,4,5-trimethoxybenzoic acid 8-(diethylamino)-octyl ester (TMB-8), a putative antagonist of Ca release from intracellular sequestration sites. The rat renal cortical slices preparation was used. Basal renin secretory rate was unaffected by 1 and 10 μM TMB-8, but more than doubled in response to 100 μM TMB-8. Basal renin secretory rate was inhibited by A-II (1 μM), by ADH (200 units/1), by an A 1-adenosine receptor agonist (N 6-cyclohexyladonosine, or CHA; 0.5 μM), and by an α-adrenergic agonist (methoxamine; 10 μM). Only the inhibitory effect of methoxamine was blocked by 1 and 10 μM TMB-8, but these concentrations had no effect on basal secretory rate. At 100 μM, TMB-8 blocked the inhibitory effects of ADH as well as of methoxamine, but failed to block the inhibitory effects of CHA and A-II. However, these observations cannot be taken as evidence that methoxamine and ADH, but not CHA and A-II, inhibit renin secretion by a mechanism involving release of Ca from intracellular sequestration sites, because 100 μM TMB-8 clearly had non-specific effects. Among them, it completely blocked the inhibitory effect of K-depolarization on renin secretion. Collectively, at least three separate actions of TMB-8 must be invoked to explain the present results. Likely candidates are an Na-channel blocking effect and a Ca channel blocking effect in addition to antagonism of the release of Ca 1.

Effect of acute stimulation of renin secretion on renal renin content in vivo

Acute stimulation of renal renin secretion has been reported to increase, not change, or decrease intra-renal renin (IRR) content. However, these effects and the potential mechanisms for acute changes in IRR content have not been studied directly. In this study, the effect of acute stimulation of renin secretion on IRR content was studied directly using a new in vivo blood perfused rabbit kidney preparation. Following removal of the right kidney for determination of IRR content (N = 7) the left kidney was cannulated and perfused for an average of 55 minutes (baseline) at mean arterial blood pressure. Renin secretion by the left kidney was subsequently stimulated by reducing renal perfusion pressure to 60 mm Hg and administering enalapril, 1 mg/kg intravenously. After 38 to 140 minutes (mean 90 min) of stimulation, the left kidney was also removed and IRR content assessed. Renal blood flow and renin secretory rate (RSR) were determined frequently at baseline and following stimulation of renin secretion. The total amount of renin secreted in response to acute stimulation was calculated by integrating the RSR response over time. RSR from the left kidney increased by 515% during acute stimulation. IRR content in the left kidney also increased and averaged 16% greater than the right kidney from the same animal. In order to account for all of the renin secreted as well as the increase in IRR content following acute stimulation, it was calculated that the renin synthesis rate would have been required to increase over 26-fold.(ABSTRACT TRUNCATED AT 250 WORDS)

Characterization of the macula densa stimulus for renin secretion

These studies utilize the isolated perfused rabbit juxtaglomerular apparatus (JGA) to study the macula densa signal for renin secretion in the absence of the confounding influences of intravascular pressure and renal nerve activity. In the first experimental series, JGAs were perfused alternately with high- and low-NaCl solutions to determine the reversibility of the renin response to changes in NaCl concentration. Compared with high-NaCl controls, perfusion with a low-NaCl solution resulted in a fivefold increase in renin secretion rate (RSR) [2.1-10.0 nano-Goldblatt hog units (nGU)/min], and this response was largely reversible. When the solutions were presented in the reverse order, a similar inhibition by high NaCl was observed. In the second series, JGAs were perfused with high-, medium-, and low-NaCl solutions to determine the sensitive range of the renin response to NaCl concentration changes. The full renin response (3.2-16.6 nGU/min), similar in magnitude to that seen in series 1, was found to occur between 80 and 24 mM for Na+ and 61 and 7 mM for Cl-. In the third series, the NaCl concentration and flow rate of the perfusate were altered independently to separate the effects of flow rate, NaCl delivery, and NaCl concentration on RSR. Although a decrease in perfusate flow rate slightly increased RSR (3.4-8.1 nGU/min), a comparable decrease in NaCl concentration resulted in a much higher RSR (26.3 nGU/min). We conclude that in this preparation 1) RSR responds equally to both increases and decreases in macula densa NaCl concentration, and these changes are rapid and largely reversible, 2) the full renin response occurs within the concentration range normally occurring at the macula densa, i.e., below 80 mM Na+ and 61 mM Cl-, and 3) RSR responds with a larger change to alterations in NaCl concentration than in NaCl delivery or fluid flow rate.

Measurement of renin secretion in single perfused rabbit glomeruli

A new technique is presented that allows the measurement of the renin secretion rate of single rabbit glomeruli during in vitro perfusion at controlled afferent arteriolar perfusion pressure. Rabbit glomeruli with intact afferent arteriole and Bowman's capsule are obtained by microdissection and cannulated with a pipette system that allows continuous afferent arteriolar pressure measurement. The renin secretion rate of 10 glomeruli, perfused at 40 mmHg, was measured in 15-min intervals with an antibody-trapping microassay. Renin secretion rate was low relative to total renin content (1.2-2.0% of content/perfusion h) and increased three- to fivefold in response to isoproterenol (10(-5) M). The afferent arteriole contracted to norepinephrine (10(-5) M) in each instance. This novel, although difficult, technique allows the study of renin release in vitro at controlled perfusion pressure, without the interfering effects of the macula densa, arterial angiotensin II, and the adrenergic nervous system. It should allow a new perspective on issues such as the pressure-flow dependence of renin release and the interaction of the afferent arteriolar endothelium with the renin-secreting juxtaglomerular cells.

Effect of adenosine1-receptor blockade on renin release from rabbit isolated perfused juxtaglomerular apparatus.

Adenosine has been proposed to act within the juxtaglomerular apparatus (JGA) as a mediator of the inhibition of renin secretion produced by a high NaCl concentration at the macula densa. To test this hypothesis, we studied the effects of the adenosine1 (A1)-receptor blocker 8-cyclopentyl-1,3-dipropylxanthine (CPX) on renin release from single isolated rabbit JGAs with macula densa perfused. The A1-receptor agonist, N6-cyclohexyladenosine (CHA), applied in the bathing solution at 10(-7) M, was found to inhibit renin secretion, an effect that was completely blocked by adding CPX (10(-5) M) to the bath. Applied to the lumen, 10(-5) M CPX produced a modest stimulation of renin secretion rates suppressed by a high NaCl concentration at the macula densa (P less than 0.05). The effect of changing luminal NaCl concentration on renin secretion rate was examined in the presence of CPX (10(-7) and 10(-5) M) in the bathing solution and in vehicle control experiments. The control response to increasing luminal NaCl concentration was a marked suppression of renin secretion, that was maintained as long as luminal NaCl concentration was high and was promptly reversible when concentration was lowered. CPX did not alter renin release when luminal NaCl was low, but diminished the reduction caused by high NaCl (P less than 0.01). It is concluded that A1-receptors are located within the JGA, and that A1-receptor activation inhibits renin release. A high NaCl concentration at the macula densa appears to influence A1-receptor activation, but a low NaCl concentration does not. The findings support participation of adenosine in macula densa control of renin secretion.

Do Calcium-Activated Chloride Channels Control Renin Secretion?

The rate of renin secretion from renal juxtaglomerular epithelioid cells appears to be inversely correlated to intracellular Ca activity. Such a dependency of renin secretion on Ca activity could be controlled by Ca-activated Cl channels that may be involved in the volume control of juxtaglomerular cells.

Renin secretion by fetal lamb kidneys in vitro

We studied the content and secretion of renin by renal cortical slices obtained from ovine fetuses at 0.62-0.77 gestation (n = 5 immature) and at 0.84-1.00 gestation (n = 5 mature). Renin content of fresh slices and renin secretion after the incubation of slices in Robinson's medium with or without isoproterenol or dibutyryl (DB) adenosine 3',5'-cyclic monophosphate (cAMP) (10(-4)-10(-8) M) were measured. Renin content of immature fetal kidneys (ng.ml homogenate-1.h-1.mg-1) and basal renin secretion rate [ng (ANG I/h).mg tissue-1.h incubation-1] were 24.3 +/- 3.0 and 1.4 +/- 0.4, respectively. Both of these values were significantly lower (P less than 0.02) than the corresponding results obtained with mature fetal kidneys (67.0 +/- 4.5 and 3.4 +/- 0.5). Renin content and basal secretion rates were strongly correlated (r = 0.78, P less than 0.01). The addition of isoproterenol or DBcAMP induced a significant increase in renin secretion only when incubated with slices from mature fetuses. We conclude that there is a deficit in the beta-adrenoceptor-mediated renin release distal to cAMP formation in immature fetuses, which may be related to low renal content of renin at this stage of development.

Vanadate-induced inhibition of renin secretion is unrelated to inhibition Na,K-ATPase activity

There is evidence that three inhibitors of Na,K-ATPase activity--ouabain, K-free extracellular fluid, and vanadate--inhibit renin secretion by increasing Ca 2+ concentration in juxtaglomerular cells, but in the case of vanadate, it is uncertain whether the increase in Ca 2+ is due to a decrease in Ca 2+ efflux (inhibition of Ca-ATPase activity, or inhibition of Na,K-ATPase activity, followed by an increase in intracellular Na + and a decrease in Na-Ca exchange) or to an increase in Ca 2+ influx through potential operated Ca channels (inhibition of electrogenic Na,K transport, followed by membrane depolarization and activation of Ca channels). In the present experiments, the rat renal cortical slice preparation was used to compare and contrast the effects of ouabain, of K-free fluid, and of vanadate on renin secretion, in the absence and presence of methoxyverapamil, a Ca channel blocker. Basal renin secretory rate averaged 7.7 ± 0.3 GU/g/60 min, and secretory rate was reduced to nearly zero by 1mM ouabain, by K-free fluid, by 0.5 mM vanadate, and by K-depolarization (increasing extracellular K + to 60 mM). Although 0.5 μM methoxyverapamil completely blocked the inhibitory effect of K-depolarization, it failed to antagonize the inhibitory effects of ouabain, of K-free fluid, and of vanadate. A concentration of methoxyverapamil two hundred times higher (100 μM) completely blocked the inhibitory effects of vanadate, but still failed to antagonize the effects of ouabain and of K-free fluid. Collectively, these observations demonstrate that vanadate-induced inhibition of renin secretion cannot be attributed entirely to Na,K-ATPase inhibition, since in the presence of methoxyverapamil, the effect of vanadate differed from the effects of either ouabain (a specific Na,K-ATPase inhibitor) or K-free fluid. Moreover, it cannot be attributed entirely to a depolarization-induced influx of Ca 2+ through potential-operated Ca channels, since methoxyverapamil antagonized K-depolarization-induced inhibition of renin secretion much more effectively than it antagonized vanadate-induced inhibition.

Nephron heterogeneity: clue to the pathogenesis of essential hypertension and effectiveness of angiotensin-converting enzyme inhibitor treatment.

It is proposed that in essential hypertension there are two functionally abnormal populations of nephrons. One is ischemic; chronically hypersecreting renin and underexcreting sodium. The other, the larger population, is in adaptive hypernatriuresis with its renin secretion chronically suppressed. Nephrons in these two populations, each with its own detector-effector apparatus for renin secretion and sodium excretion, behave according to their individual needs, producing a physiologic discordance expressed in high blood pressure even with plasma renin levels in the so-called "normal" range. The unsuppressed and inappropriate renin secretion from the ischemic nephrons impairs renal function in ischemic and hyperfiltering nephrons alike, but in very different ways. To maintain glomerular filtration rate and an adequate excretion of sodium, the ischemic nephrons require a higher rate of renin secretion than they are actually receiving, because at low perfusion pressures maximal angiotensin II-induced efferent arteriolar constriction is needed to maintain glomerular filtration rate. On the other hand, the compensating hypernatriuretic nephrons become unable fully to excrete dietary sodium because they are exposed to an unwanted, inappropriately high angiotensin II level coming from the ischemic nephrons. This angiotensin II impairs sodium excretion (adaptive hypernatriuresis) from unaffected, adapting nephrons by promoting proximal sodium reabsorption and by inducing afferent constriction. The net result is that all nephrons are exposed to angiotensin II levels inappropriate for their needs. This leads to impaired ability to excrete sodium by both populations of nephrons, with sodium retention in the presence of abnormal renin secretion and perpetuation of the hypertension. The hypothesis is consistent with the hallmark pathology of multifocal afferent arteriolar narrowing seen in essential hypertension as well as with the characteristic renal hemodynamic pattern of vasoconstriction with reduced renal blood flow but with maintained glomerular filtration rate. The "normal" glomerular filtration rate as well as the often "normal" plasma renin activity may be seen as the sum of effects on the two abnormally acting populations of nephrons. Further, since any circulating renin is inappropriate in the presence of hypertension, the hypothesis helps explain why angiotensin-converting enzyme inhibitors reduce blood pressure even when renin levels are not elevated.

Nephron heterogeneity: Clue to the pathogenesis of essential hypertension and effectiveness of angiotensin-converting enzyme inhibitor treatment

It is proposed that in essential hypertension there are two functionally abnormal populations of nephrons. One is ischemic; chronically hyper-secreting renin and underexcreting sodium. The other, the larger population, is in adaptive hyper-natriuresis with its renin secretion chronically suppressed. Nephrons in these two populations, each with its own detector-effector apparatus for renin secrétion and sodium excretion, behave according to their individual needs, producing a physiologic discordance expressed in high blood pressure even with plasma renin levels in the so-called “normal” range. The unsuppressed and inappropriate renin secretion from the ischemic nephrons impairs renal function in ischemic and hyperfiltering nephrons alike, but in very different ways. To maintain glomerular filtration rate and an adequate excretion of sodium, the ischemic nephrons require a higher rate of renin secretion than they are actually receiving, because at low perfusion pressures maximal angiotensin II-induced efferent arteriolar constriction is needed to maintain glomerular filtration rate. On the other hand, the compensating hyper-natriuretic nephrons become unable fully to excrete dietary sodium because they are exposed to an unwanted, inappropriately high angiotensin II level coming from the ischemic nephrons. This angiotensin II impairs sodium excretion (adaptive hypernatriuresis) from unaffected, adapting nephrons by promoting proximal sodium reabsorption and by inducing afferent constriction. The net result is that all nephrons are exposed to angiotensin II levels inappropriate for their needs. This leads to impaired ability to excrete sodium by both populations of nephrons, with sodium retention in the presence of abnormal renin secretion and perpetuation of the hypertension. The hypothesis is consistent with the hallmark pathology of multifocal afferent arteriolar narrowing seen in essential hypertension as well as with the characteristic renal hemodynamic pattern of vasoconstriction with reduced renal blood flow but with maintained glomerular filtration rate. The “normal” glomerular filtration rate as well as the often “normal” plasma renin activity may be seen as the sum of effects on the two abnormally acting populations of nephrons. Further, since any circulating renin is inappropriate in the presence of hypertension, the hypothesis helps explain why angiotensin-converting enzyme inhibitors reduce blood pressure even when renin levels are not elevated. It is proposed that in essential hypertension there are two functionally abnormal populations of nephrons. One is ischemic; chronically hyper-secreting renin and underexcreting sodium. The other, the larger population, is in adaptive hyper-natriuresis with its renin secretion chronically suppressed. Nephrons in these two populations, each with its own detector-effector apparatus for renin secrétion and sodium excretion, behave according to their individual needs, producing a physiologic discordance expressed in high blood pressure even with plasma renin levels in the so-called “normal” range. The unsuppressed and inappropriate renin secretion from the ischemic nephrons impairs renal function in ischemic and hyperfiltering nephrons alike, but in very different ways. To maintain glomerular filtration rate and an adequate excretion of sodium, the ischemic nephrons require a higher rate of renin secretion than they are actually receiving, because at low perfusion pressures maximal angiotensin II-induced efferent arteriolar constriction is needed to maintain glomerular filtration rate. On the other hand, the compensating hyper-natriuretic nephrons become unable fully to excrete dietary sodium because they are exposed to an unwanted, inappropriately high angiotensin II level coming from the ischemic nephrons. This angiotensin II impairs sodium excretion (adaptive hypernatriuresis) from unaffected, adapting nephrons by promoting proximal sodium reabsorption and by inducing afferent constriction. The net result is that all nephrons are exposed to angiotensin II levels inappropriate for their needs. This leads to impaired ability to excrete sodium by both populations of nephrons, with sodium retention in the presence of abnormal renin secretion and perpetuation of the hypertension. The hypothesis is consistent with the hallmark pathology of multifocal afferent arteriolar narrowing seen in essential hypertension as well as with the characteristic renal hemodynamic pattern of vasoconstriction with reduced renal blood flow but with maintained glomerular filtration rate. The “normal” glomerular filtration rate as well as the often “normal” plasma renin activity may be seen as the sum of effects on the two abnormally acting populations of nephrons. Further, since any circulating renin is inappropriate in the presence of hypertension, the hypothesis helps explain why angiotensin-converting enzyme inhibitors reduce blood pressure even when renin levels are not elevated.

Effects of endothelin on renal function and renin secretion in anesthetized rats

The infusion of endothelin into the renal artery of anesthetized rats at 1 ng/kg per min, a dose with no influence on renal function, had no effect on the basal levels of plasma renin activity (PRA) and renin secretory rate (RSR), but significantly inhibited the isoproterenol-induced increases in PRA and RSR. Endothelin, 2 ng/kg per min, elicited significant decreases in renal hemodynamics and in urine formation but the mean arterial pressure was not affected. The possibility that endothelin may participate in controlling renal function and renin secretion in vivo warrants further attention.

Ontogeny of isoproterenol-stimulated renin secretion from sheep renal cortical slices

The ontogeny of renin secretion from renal cortical slices was studied in two groups of fetal (107-109 days of gestation and 131-136 days of gestation; term is 145 days), newborn (3-9 days old), and adult nonpregnant sheep. Isoproterenol (ISO; 10(-8)-10(-5) M) significantly increased active renin secretion in all age groups (P less than 0.05), with newborns having the highest values at all concentrations. However, the percent changes in active renin secretion were similar among all ages. Inactive renin secretion also increased with ISO stimulation, with newborns having the highest rate of inactive renin secretion. The percent of total renin in the active form differed among ages, ranging at base line from 60 +/- 10% in fetuses at greater than 130 days of gestation to 88 +/- 6% in fetuses at less than 110 days of gestation (P less than 0.05). Propranolol (1 microM) inhibited ISO (10(-6) M)-stimulated active renin secretion at all ages. On the other hand, the prostaglandin (PG) synthase inhibitor aspirin (1.6 x 10(-5) M) did not inhibit ISO (10(-6) M)-mediated increases in active renin secretion in fetal (greater than 130 days of gestation) kidney slices and produced values intermediate between base line and ISO alone in newborns and adults.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine inhibits renin release induced by suprarenal-aortic constriction and prostacyclin

The purpose of this study was to determine whether adenosine can attenuate the renin release response to a reduction in renal perfusion pressure. To this end, the secretion rate of renin was measured in six beta-blocked dogs at ambient arterial blood pressure and after a reduction of renal perfusion pressure to 80 mm Hg. These measurements were made during a control period, an intrarenal infusion of adenosine at 10 and 30 micrograms/min, and a recovery period. During the control and recovery periods renal artery hypotension significantly increased the secretion rate of renin. However, during the intrarenal infusions of adenosine, renin secretion rate did not increase significantly. Analysis of variance indicated that both doses of adenosine reduced the renin response to renal artery hypotension. In another six dogs with a single nonfiltering kidney, we again measured renin secretion during a control period, the intrarenal infusion of adenosine at 10 and 30 micrograms/min, and a recovery period; however, in this study PGI2 was used to stimulate renin release. Adenosine also significantly attenuated the renin release response to PGI2. We conclude that adenosine can inhibit the renin release response to both renal artery hypotension and PGI2 and that this effect is most likely mediated by a direct action of adenosine on juxtaglomerular cells. Also, since PGI2 may be a mediator of the renin response to renal artery hypotension, the data are consistent with the hypothesis that adenosine inhibits the renin response to renal artery hypotension by attenuating the response of juxtaglomerular cells to PGI2.

Role of adrenoceptors in diphenylhydantoin-stimulated renin release.

We have previously shown that diphenylhydantoin (DPH)-stimulated renin release is mediated by, or requires the presence of, the renal nerves. In the present study, we examined the effects of adrenergic blockers in DPH-stimulated renin release in five groups of anesthetized dogs. In vehicle-treated dogs, DPH at a dose of 0.18 mg/kg-min increased renin secretion rate (RSR) from 56 +/- 14 to 269 +/- 60 and returned to 84 +/- 30 ng of angiotensin (ANG) l/hr-min (P less than 0.01, analysis of variance). In metoprolol-treated dogs, DPH produced no significant changes in RSR (90 +/- 28 to 144 +/- 67 to 100 +/- 51 ng of ANG l/hr-min). Likewise, in atenolol-treated dogs, RSR was 34 +/- 10 before, 59 +/- 15 during, and 23 +/- 8 ng of ANG l/hr-min after the infusion of DPH. In contrast, after pretreatment with ICI 118,551 (a beta 2 adrenoceptor antagonist), RSR was 37 +/- 9 before, 151 +/- 57 during, and 47 +/- 12 ng of ANG l/hr-min after the infusion of DPH (P less than 0.01). In phentolamine-treated dogs, RSR was 69 +/- 20 before, 295 +/- 53 during, and 95 +/- 17 ng of ANG l/hr-min after the infusion of DPH (P less than 0.01). Changes in renal blood flow, renal vascular resistance, and UNa V were in the same directions in all groups. These data suggest that DPH-stimulated renin release is mediated by beta 1 adrenoceptors since both beta 2 and alpha adrenoceptor antagonists have no effects on DPH-stimulated renin release.

Renal actions of neuropeptide Y in the primate.

Neuropeptide Y (NPY) is a potent vasoconstrictor peptide contained in sympathetic nerve terminals and is co-released with norepinephrine. Previous studies in the rat have suggested that NPY influences renal sodium reabsorption and renin release. However, little is known about the physiological effects of NPY on the kidney in the human. In the present study NPY was infused intravenously and directly into the renal artery of the primate Macaca fascicularis, an experimental model of the human. Intravenous NPY infusion at doses of 20-1,000 ng.kg-1.min-1 produced dose-dependent rises in renal vascular resistance with minimal changes in arterial pressure. Urine flow and sodium excretion were changed significantly only at doses of NPY that significantly reduced renal blood flow and filtration rate. Arterial plasma renin activity and renin secretion rate were not significantly altered at any dose of NPY. Intrarenal infusion of NPY at doses of 20-400 ng.kg-1.min-1 produced potent dose-dependent renal vasoconstriction with minimal changes in arterial pressure. Under these conditions sodium excretion was significantly reduced concurrent with decreases in renal blood flow and glomerular filtration rate. However, no significant changes in arterial plasma renin activity or renin secretion rate were found at any dose of NPY. These data indicate that in the nonhuman primate NPY is a potent renal vasoconstrictor agent that has variable effects on renal excretory and secretory function, which may be secondary to its vasoconstrictor actions.

Processing of one-chain to two-chain renin in the mouse submandibular gland is influenced by androgen.

In the male CD-1 mouse submandibular gland (SMG) renin activity increases markedly with puberty. We have reported that this is, in part, due to an androgen-mediated increase in renin gene transcription. In this study, we examined whether posttranslational processing is also influenced by androgen. We studied secretion and processing of active renin in the CD-1 male mouse SMG which secretes primarily the Ren-2 renin isozyme before and after puberty and also compared findings with the adult female CD-1 mouse. Maturation increases renin level and secretion rate in the male SMG but much less in the female. In addition, Western blot analysis of molecular forms of renin in SMG tissue and media shows a predominance of 1-chain intermediate form of renin before puberty but of the 2-chain mature form thereafter. Adult female SMG contains and secretes much less active renin than the male organ. Administration of testosterone to the female CD-1 mouse induces an adult male level and pattern of secretion, with high concentrations of active 2-chain renin being secreted. These data suggest that SMG renin is androgen regulated, in part by an androgen-responsive enzyme that processes 1-chain renin to the 2-chain form.

Sympathetic nervous system influences on the kidney. Role in hypertension.

Efferent renal sympathetic nerve activity (ERSNA) is elevated in human essential hypertension as well as several forms of experimental hypertension in animals. In addition, bilateral complete renal denervation delays the development and/or attenuates the magnitude of the hypertension in several different forms of experimental hypertension in animals. Efferent renal sympathetic nerve activity is known to have dose-dependent effects on renal blood flow and glomerular filtration rate, renal tubular sodium and water reabsorption, and renin secretion rate that are capable of contributing, singly or in combination, to the development, maintenance, and exacerbation of the hypertensive state. Of the many factors known to influence the central nervous system integrative regulation of ERSNA, two environmental factors, dietary sodium intake and environmental stress, are capable of significant interaction. This resultant increase in ERSNA and subsequent renal functional alterations can participate in the hypertensive process. This is especially evident in the presence of an underlying genetic predisposition to the development of hypertension. Thus, interactions between environmental and genetic influences can produce alterations in the sympathetic neural control of renal function that play an important role in hypertension.

Neural control of renin release.

Among the major mechanisms controlling the renal release of renin, renal nerves are known to exert a direct stimulating action on juxtaglomerular cells that is mediated by beta-adrenoceptors. Activation of the renal nerves also exerts an important permissive role in order to amplify and possibly accelerate responses to stimuli affecting the vascular and macula densa mechanisms. Reduction of renal perfusion pressure, intravenous infusion of furosemide, and captopril administration cause a greater increase in renin release from innervated kidneys than from denervated kidneys. A complex interaction between neural and non-neural mechanisms in the control of renin secretion is suggested. Efferent renal nerve activity controlling the renin secretion rate is mainly under the inhibitory influence of vagal afferent fibers originating from the cardiopulmonary region. Recent experiments have demonstrated that a similar reflex tonic inhibition of renin secretion is also exerted by renal afferent fibers.

Effects of bay K 8644 on renal functions 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 μg/kg/min had no effect on renal blood flow (RBF) and glomerular filtration rate (GFR), but decreased urine flow (UF), urinary sodium excretion (U NaV) and fractional sodium excretion (FE Na) by about 30%, 55% and 35%, respectively, thereby suggesting that Bay K 8644 enhanced the tubular reabsorption of water and sodium. When 10 μg/kg/min were infused, RBF, GFR, UF, U NaV and FE Na decreased to about 95%, 70%, 35% and 30% of each control value. The administration of Bay K 8644 at 10 μg/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 volatage-dependent calcium channels with Bay K 8644 influences the control of renal function and renin secretion in vivo.