Renin Secretion Rate Research Articles

Ca<sup>2+</sup> 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 atrial natriuretic factor on urinary concentration of catecholamines and renin secretion in dogs

This study evaluated the effects of synthetic atrial natriuretic factor (ANF) on renal hemodynamics, urinary excretion of electrolytes, norepinephrine (NE), and dopamine (DA); and renal production of renin in anesthetized dogs. Following a bolus (1 micrograms/kg body weight) and infusion (0.1 microgram/kg/min) for 30 min, there was significant increase in urine flow (220 +/- 41%), glomerular filtration rate (72 +/- 14%), and urinary sodium excretion (170 +/- 34%). There was a decrease in renin secretory rate and the concentration ratio of urine NE to DA following ANF was decreased (p less than 0.05). These data suggest that ANF decreases renal production of NE and renin.

Renal hemodynamics in response to a kinin analogue antagonist.

The influence of endogenous kinins on renal hemodynamics was studied using a kinin analogue antagonist ([DArg0-Hyp3-Thi5-DPhe7-Thi8]bradykinin) in eight sodium-restricted anesthetized dogs. Clearance periods were run during intrarenal infusion of vehicle or 50 micrograms/min of analogue during normal and reduced renal perfusion pressure within (95 mmHg) and below (65 mmHg) the range of renal autoregulation. During normal renal perfusion, the analogue did not affect arterial pressure, glomerular filtration rate (GFR), or sodium excretion but decreased renal blood flow (RBF) by 20% (6.41 +/- 0.35 vs. 5.61 +/- 0.38 ml.min-1.g kidney wt-1, P less than 0.05) due to increased renal vascular resistance (RVR, 0.44 +/- 0.03 vs. 0.54 +/- 0.04 U, P less than 0.01). The analogue increased renin secretion rate (RSR, 311 +/- 190 vs. 654 +/- 202 ng angiotensin I/min, P less than 0.001). With reduced renal perfusion (95 mmHg), RBF was unchanged, and sodium excretion and RVR decreased. Vehicle did not change GFR, but the analogue abolished autoregulation of GFR (-37%, P less than 0.02) and decreased filtration fraction (24 +/- 4 vs. 34 +/- 4%, P less than 0.05). Renal perfusion pressure of 65 mmHg decreased RBF, GFR, and sodium excretion similarly with vehicle or analogue. Converting-enzyme inhibition eliminated the changes in RVR. Thus kinin antagonism increased RSR and consequently RVR at normal renal perfusion. As renal perfusion pressure decreased, kinin antagonism diminished autoregulation of GFR but not of RBF. These results suggest that kinin antagonism may either modify the arteriolar resistance or alter the coefficient of filtration, resulting in decreased GFR at reduced renal perfusion pressure.

Epinephrine-induced renin secretion is not initiated by cardiac adrenoceptors.

Experiments were designed to test the hypothesis that epinephrine may act directly on cardiac or pulmonary adrenoceptors to alter the release of a humoral substance that in turn influences renin secretion. Accordingly, anesthetized dogs were prepared with catheters for infusion of epinephrine at three sites: 1) into the aorta just distal to the left subclavian artery, 2) into the left ventricle, and 3) near the right atrium. Left renal renin secretion rates were determined before, during, and after 30-min infusions of epinephrine at each site in each animal; the order of the infusions was randomized. At epinephrine infusion rates of 15 and 75 ng.kg-1.min-1, epinephrine-induced changes in renin secretion rates were dose dependent but were independent of the site of infusion. These data do not support the hypotheses that either pulmonary or cardiac adrenoceptors are involved in the initiation of epinephrine-induced renin secretion. In additional experiments, an isolated canine heart was perfused with femoral arterial blood from an experimental dog, and the coronary venous effluent was returned to the experimental dog via the femoral vein. Intravenous epinephrine infusion at 50 ng.kg-1.min-1 increased plasma renin activity nearly 1.5-fold. In contrast, plasma renin activity did not increase during infusion of epinephrine at 5 ng.kg-1.min-1 directly into the coronary perfusate of the isolated heart. Coronary perfusate epinephrine concentration was 699 +/- 71 pg/ml (mean +/- SE) during intravenous infusion and was 851 +/- 121 pg/ml during direct infusion of epinephrine into the coronary perfusate. We conclude that cardiac adrenoceptors do not participate in the initiation of epinephrine-induced renin secretion.

Effects of thromboxane synthase inhibitors on renal function.

In general the effects of thromboxane A2(TXA2) on renal function are opposite those produced by other prostanoids. TXA2 synthase inhibitors decrease the biosynthesis of TXA2 and may increase the production of other prostanoids by causing endoperoxide shunting. Therefore, in situations of increased kidney arachidonate mobilization, inhibition of renal TXA2 synthase might alter renal function by reducing TXA2 production and/or increasing prostaglandin (PG) biosynthesis. This hypothesis was tested by comparing the changes in renal function induced by suprarenal aortic constriction in anesthetized dogs pretreated with either a TXA2 synthase inhibitor (UK38,485; n = 7 or OKY1581; n = 7) or vehicle (0.1 M Na2CO3; n = 9). Several renal function parameters were compared in control versus treated animals by analysis of variance. Neither UK38,485 (1 mg/kg, i.v.) nor OKY1581 (10 mg/kg, i.v.) significantly altered renal artery hypotension-induced changes in mean arterial blood pressure, heart rate, renal blood flow, renal vascular resistance, glomerular filtration, filtration fraction, urine flow rate, sodium excretion rate, fractional sodium excretion, potassium excretion, or fractional potassium excretion. However, both UK38,485 and OKY1581 seemed to attenuate the increase in renal renin secretion rate induced by suprarenal aortic constriction. We conclude that acute administration of TXA2 synthase inhibitors does not modify acute renal artery hypotension-induced changes in either electrolyte excretion or renal hemodynamics. However, acute administration of TXA2 inhibitors attenuates suprarenal aortic constriction-induced increases in renin release in anesthetized dogs by unknown mechanisms.

Cellular mechanisms of renin release.

The renin-angiotensin system plays a central role in salt and water balance and in the regulation of arterial blood pressure. The level of activity of this system is determined primarily by the rate at which the granulated juxtaglomerular cells (JG cells) secrete renin into the blood. Physiologically, renin secretory rate is controlled by a number of first messengers: afferent arteriolar transmural pressure or some function of it, such as stretch (the baroreceptor mechanism); solute transport in the macula densa segment of the nephron (the macula densa mechanism); catecholamines released from the renal nerves and the adrenal medulla (the beta-adrenergic mechanism); extracellular concentrations of many organic and inorganic substances including angiotensin II, vasopressin, K, and Mg (1-3). In addition to these physiological first messengers, a number of pharmacological agents affect renin secretion (3). It is an accepted principle of cellular biology that first messengers act by affecting the intracellular concentrations of only a few second messengers. The evidence that intracellular free ionic calcium, cyclic AMP, and cyclic GMP are second messengers in renin secretion has been reviewed in detail recently (4-9). These reviews are cited extensively, since space limitations precluded citing all the original literature.

Direct release of angiotensins I and II from isolated rat kidney perfused with angiotensinogen-free medium

A direct measurement of both angiotensins I and II immunoreactive substances was made in the perfusate from isolated rat kidney perfused with Krebs-Ringer solution which was free of any component of the renin-angiotensin system. The identity of the immunoreactive peptides was confirmed as angiotensin I and angiotensin II by high-pressure liquid chromatography in reference to standard compounds. The rate of release of angiotensins was as high as 1313.5 ± 184.5 and 772.4 ± 82.5 pg for angiotensins I and II, respectively, during the first perfusion period of 20 min, and it remained stable at least for 2 hours. There was a good relationship between the angiotensin I secretion rate and renin secretion rate simultaneously determined in the perfusate, and also between the angiotensin I secretion rate and angiotensin II secretion rate. These results taken together with the previous observations of the coexistence of renin and angiotensins I and II in juxtaglomerular cells of the kidney provide evidence for intrarenal formation and release of angiotensin II. It does not agree with the notion that these peptides are internalized from circulation. Angiotensin II secreted from the kidney may play diverse functions in intrarenal regulation.

Role of prostaglandin in norepinephrine and renin release in canine kidney.

We investigated renin and norepinephrine (NE) release during electrical renal nerve stimulation (RNS) in relation to prostaglandin (PG) E2 concomitantly produced by the kidney in anesthetized dogs. During 10 min of continuous RNS (2.5-4 Hz), the increases in renin, NE, and PGE2 secretion rates were determined at 1 and 10 min after the start of stimulation. Under control conditions, almost the same extent of increase in the NE secretion rate was observed at 1 and 10 min of RNS, whereas the increase in renin secretion rate at 1 min of RNS was followed by a further increase at 10 min of RNS. On the other hand, an upward but not significant trend of increase in PGE2 secretion at 1 min of RNS was followed by a substantial level at 10 min of RNS. After administration of indomethacin, the increase in NE secretion rates at both 1 and 10 min of RNS were not altered, but the increase in renin secretion rate at 10 min of RNS was suppressed by approximately 50%, without any reduction of the increase in the renin secretion rate at 1 min of RNS. Consequently, the time-related change in the renin secretion rate during RNS was abolished. These results suggest that renin response to continuous RNS is enhanced by concomitantly generated PGs but not by NE, and furthermore, that endogenously generated PGs do not inhibit the release of NE from canine renal nerve endings.

Effects of angiotensin I converting enzyme inhibition and calcium channel blockade on plasma levels of active and inactive renin in conscious rabbits

The interplay of juxtaglomerular (jg) calcium fluxes and exposure to AII in the regulation of jg renin secretion, was examined in vivo. An inhibitor of angiotensin I converting enzyme (captopril), a blocker of calcium channels (verapamil) and AII amide were infused, singly or in combination, into the ear vein of conscious rabbits. The effects on arterial pressure, and on levels of active and inactive plasma renin were monitored. Captopril (50 μg · min −1 · kg −1) produced a greater percentage increase in renin secretion than did verapamil (20 μg · min −1· kg −1), whilst the percentage fall in arterial pressure was similar. AII amide counteracted more effectively the actions of captopril than those of verapamil. When captopril was infused first, addition of verapamil did not enhance renin secretion (P > 0.2). When verapamil was infused first, addition of captopril greatly enhanced renin secretion (P < 0.01). However, when captopril was infused first, and its actions then suppressed by AII amide, addition of verapamil led to extremely high rates of renin secretion. The findings suggest the following: (1) the short loop negative feedback plays in vivo an important role in the rapid modulation of jg renin secretion and the action of AII may involve up- and down-regulation at the receptor and/or post-receptor level; (2) infused agents have rapid access to the critical sites of jg cells; (3) exposure to raised concentrations to AII not only reduces the effectiveness of AII, but also enhances jg secretory responses to lack of AII, as well as to calcium channel blockade. Thus, at least some of the jg calcium channels appear to respond both to AII and to blockers; (4) extreme changes in the levels of active renin are possible without changes of inactive renin levels. Secretion of the latter may be under separate control, or its secretion rate parallelled by the rate of its activation.

De novo intrarenal formation of angiotensin II during control and enhanced renin secretion.

In previous studies it has not been possible to determine net intrarenal formation of angiotensin II (ANG II) from arteriovenous ANG II concentrations because of the high intrarenal ANG II degradation rates (DR). This study was designed to determine ANG II-DR and to estimate net intrarenal ANG II formation during normal and enhanced renin secretion rate (RSR). In anesthetized dogs, plasma renin activity and ANG II were measured in arterial and renal venous blood by radioimmunoassay during four periods: control, renal arterial constriction (RAC), angiotensin converting enzyme (ACE) inhibition (MK 422), and MK 422 plus systemic arterial ANG II infusion. ANG II-DR was determined in each dog from the arterial-renal venous ANG II concentration difference during the period of ANG II infusion in the presence of ACE inhibition; this value was used to estimate net ANG II formation by predicting the amount of arterially delivered ANG II that escaped degradation. The average percent ANG II-DR calculated during ANG II infusion (range of 0.05 to 0.20 microgram/min) was 89 +/- 2%. In response to RAC, RSR increased from 11 +/- 3 to 24 +/- 5 ng ANG I X h-1 X min-1 X g-1. Arterial ANG II (67 +/- 11 pg/ml) and renal venous ANG II (29 +/- 6 pg/ml) increased to 133 +/- 18 and 61 +/- 10 pg/ml, respectively. Net intrarenal ANG II formation increased from 44 +/- 11 to 83 +/- 13 pg X min-1 X g-1 after renal arterial constriction. There was a significant relationship between the change in RSR and the change in ANG II formation rate.(ABSTRACT TRUNCATED AT 250 WORDS)

Role of intracellular calcium in renal nerve-mediated renin release.

We evaluated the role of intracellular calcium in renal nerve-mediated renin release in four groups of anesthetized dogs. Each dog received renal nerve stimulation (RNS)(0.5 Hz) twice as follow: control, RNS, recovery; control, RNS, recovery. Group 1 served as time control. Group 2 received Ca ionophore A23187 (Io) and Groups 3 and 4 received verapamil at 2.5 and 5 micrograms/kg X min respectively during the second RNS. In Group 1, renin secretion rate (RSR) increased from 95 +/- 22 to 223 +/- 73 (P less than 0.05) and from 13 +/- 5 to 108 +/- 20 ngANG I/hr X min (P less than 0.005) during the first and second RNS, respectively. In Group 2, RSR increased from 210 +/- 85 to 402 +/- 118 (P less than 0.02) and from 88 +/- 11 to 157 +/- 39 ngANG I/hr X min (NS) during the first and second RNS, respectively. In both groups, systemic and renal hemodynamics and UNaV did not change. In Group 3, verapamil alone did not increase RSR. During RNS, RSR also did not increase. In Group 4, verapamil alone increased RSR from 42 +/- 12 to 273 +/- 71 ngANG I/hr X min (P less than 0.03) despite a similar reduction in systemic blood pressure as in Group 3. RNS did not increase RSR further during verapamil infusion. The present study suggests that increased intracellular Ca by Io inhibits renal nerve-mediated renin release. A low dose of verapamil has no effect on renin release and does not augment renal nerve-mediated renin release. A high dose of verapamil increases renin release but does not enhance RNS-mediated renin release. We conclude that intracellular calcium plays an important role in renin release and may be the final messenger in renal nerve-mediated renin release.

Renin secretory effects of N6-cyclohexyladenosine: effects of dietary sodium.

Previous observations by others have shown that Na deprivation augments and Na loading attenuates the inhibitory effect of exogenous adenosine on renin secretion in vivo. The purpose of the present experiments was to test the hypothesis that Na deprivation and Na loading alter the sensitivity of the adenosine receptors (A1 subclass) that mediate the inhibitory effect. The rat renal cortical slice preparation was used. Na loading decreased and Na deprivation increased tissue renin content and the basal renin secretory rate; these two variables were directly related (r = 0.84, P less than 0.00005). N6-cyclohexyladenosine (CHA), an adenosine analogue that selectively activates the A1 subclass of adenosine receptors in the nanomolar to micromolar concentration range inhibited renin secretion over the same range of concentrations (nM-microM) and to approximately the same maximal extent (to 50% of the mean basal secretory rate) in cortical slices taken from Na-loaded, control, and Na-deprived rats. These results demonstrate that changes in the intrinsic sensitivity of adenosine receptors do not explain dietary Na-induced changes in the in vivo renin secretory response to exogenous adenosine.

Pertussis toxin reverses adenosine receptor-mediated inhibition of renin secretion in rat renal cortical slices

Adenosine analogs selective for the A 1 subclass of adenosine receptors, such as N 6-cyclohexyladenosine (CHA), inhibit renin secretion in vitro preparations. Ca chelation blocks the inhibitory effect, consistent with mediation by increased intracellular free Ca 2+, and it has been suggested that intracellular Ca 2+ could increase as a result of receptor-induced inhibition of adenylate cyclase followed by decreased Ca efflux from the renin-secreting cells. Pertussis toxin blocks receptor-induced inhibition of adenylate cyclase in many cells, and in others, it blocks receptor-induced phosphotidylinositol response. In the present studies, pertussis toxin treatment stimulated the basal renin secretory rate of rat renal cortical slices and blocked the inhibitory effect of CHA but not the inhibitory effect of K-depolarization. These data support the hypothesis that a pertussis toxin substrate, such as N i, is involved in CHA-, but not in K-depolarization, -induced inhibition of renin secretion.

Unilateral renal arterial infusion and renal vein catheterization in rabbits. Study of renal function and renin release.

This study evaluates the direct effects of verapamil and furosemide infused into the unilateral renal artery on renal function and the renin secretion rate in renal vein-catheterized rabbits. Catheterization did not alter the renal function parameters of the kidney. Verapamil and furosemide increased renal blood flow, urine flow, and urinary sodium, potassium and chloride excretions confined to the infused kidney. Verapamil increased the glomerular filtration rate and free water clearance. The renin secretion rate was increased by furosemide but not by verapamil. The present study shows that the technique is applicable to renal function studies in which unilateral renal arterial infusion of the agents studied is required. The contralateral kidney can be a reliable control for the infused kidney. It also provides a useful technique for the study of renin release in rabbits.

Renal and renin effects of sodium thiopental in rabbits.

Unilateral renal arterial infusion of sodium thiopental on renal function and renin secretion were investigated in unanesthetized rabbits. Sodium thiopental infusion in doses of less than 0.3 mg/kg/min into unilateral renal artery caused dose-dependent increases in urine flow, urinary excretion of electrolytes, fractional excretion of sodium and free water clearance with no changes in systemic blood pressure and clearance of p-aminohippuric acid (renal blood flow). An anesthetic dose of sodium thiopental administered intravenously caused decreases in systemic blood pressure, renal hemodynamics, urine flow and free water clearance during the early period of anesthesia followed by increases in urinary excretion of sodium and fractional excretion of sodium. Unilateral renal arterial infusion of sodium thiopental decreased the renin secretion rate and plasma norepinephrine concentration in renal vein, whereas an anesthetic dose of sodium thiopental administered intravenously increased the renin secretion rate. These observations suggest that the diuretic, natriuretic and renin suppressive effects of sodium thiopental may be due to an inhibition of intrarenal sympathetic nervous system or due to a direct tubular action.

Role of prostaglandin and angiotensin II in ANP-induced natriuresis.

The aim of the present study was to examine if the natriuresis induced by a dose of ANP that does not alter glomerular filtration rate (GFR) or mean arterial pressure (MAP) is accompanied by changes in renin release urinary excretion of prostaglandins and intrarenal blood flow distribution. It was found that the intrarenal infusion of ANP (8-33) at a dose of 0.05 micrograms/kg min in seven anaesthetized dogs did not produce any change in GFR or MAP, but its natriuretic effect was similar to that induced by a larger dose (0.3 micrograms/kg min, n = 5) that produces significant changes in both MAP and GFR. The natriuresis induced by the lower dose of ANP was associated with a redistribution of RBF to the deep cortical nephrons and with an increase (p less than 0.05) in urinary excretion of prostaglandins E2 and 6 keto-F1 alpha. Renin secretion rate decreased by a 54% (p less than 0.05). The role of angiotensin II (AII) suppression on the natriuresis induced by ANP was examine in another experimental group (n = 6). It was found that the infusion of ANP during fixed intrarenal levels of AII produced a natriuretic effect that was significantly lower (38%) than that produced by the infusion of ANP alone. The results of this study show that the natriuresis induced by ANP is not necessarily produced by an increase in GFR and is associated with a redistribution of RBF to the deep cortex an increase in urinary excretion of prostaglandins and a decrease of renin release. These results also suggest that the natriuretic effect of ANP is partly mediated by the intrarenal suppression of AII.

Involvement of calmodulin in mediating inhibitory action of intracellular Ca2+ on renin secretion.

This study sought to elucidate further the cellular mechanism(s) involved in the control of renin secretion by Ca2+. The rate of renin secretion in vitro by rabbit and dog renal cortical slices was inversely related to medium Ca2+ concentration. The inverse relationship was observed only when the cell membrane permeability to Ca2+ was increased by K+ depolarization, suggesting that the Ca2+ concentration in the juxtaglomerular cell modulates renin secretion. From this relationship, renin secretion appears to turn on at intracellular Ca2+ concentrations between 10(-8) and 10(-7) M. Calmidazolium, a potent calmodulin antagonist, markedly stimulated basal renin secretion in a concentration-dependent manner. Pretreatment of slices with calmidazolium blocked the inhibition of renin secretion by high-K+ medium. Calmidazolium and several other calmodulin antagonists (W-7, W-13, and trifluoperazine) partly or fully reversed the inhibition of renin secretion previously inhibited by high-K+ medium in the order of their potencies as calmodulin antagonists. Indeed, W-5, a biologically inactive structural analogue of W-7, was without effect. These results support the hypothesis that renin secretion is inversely related to intracellular Ca2+ and that Ca2+ inhibits renin secretion by a calmodulin-dependent process.

Renal effects of ANP without changes in glomerular filtration rate and blood pressure.

The aim of the present study was to determine if atrial natriuretic peptide (ANP)-induced natriuresis is dependent on increases in glomerular filtration rate (GFR). Intrarenal blood flow distribution and urinary excretion of prostaglandins were also determined during the infusion of a dose of ANP that does not induce changes in GFR and mean arterial pressure (MAP). It was found that the intrarenal infusion of ANP (8-33) at a dose of 0.05 micrograms X kg-1. min-1 in seven anesthetized dogs did not produce any change in GFR or MAP, but its natriuretic effect was similar to that obtained by a larger dose (0.3 micrograms X kg-1 X min-1, n = 5) that produces significant changes in both MAP and GFR. The natriuresis induced by the lower dose of ANP was associated with a redistribution (P less than 0.05) of renal blood flow (RBF) from the superficial to the juxtamedullary cortex and with an increase (P less than 0.05) in urinary excretion of prostaglandins E2 (PGE2) (0.8 +/- 0.2 to 2.4 +/- 1.0 ng/min) and 6-keto-F1 alpha (6-keto-PGF1 alpha) (2.8 +/- 0.6 to 5.5 +/- 1.7 ng/min). Renin secretion rate decreased from 610 +/- 165 to 279 +/- 61 ng angiotensin I/min. These results show that the natriuresis induced by ANP is not necessarily produced by an increase in GFR and is associated with a redistribution of RBF to the deep cortex and an increase in urinary excretion of PGE2 and 6-keto-PGF1 alpha.

Autoregulation of renal blood flow in two-kidney, one-clip hypertensive rats.

Renal blood flow (RBF) autoregulation was examined in the clipped and nonclipped kidneys in two groups of two-kidney, one-clip (2K-1C) hypertensive rats 10 wk after clipping. The arterial pressure distal to the clip and the renin secretion rate (RSR) were also examined. The blood pressure (BP) was 149 +/- 4 and 162 +/- 6 mmHg in the two hypertensive groups vs. 114 +/- 3 mmHg in the controls (P less than 0.02). The RBF (in ml X min-1 X kidney-1) was 4.27 +/- 0.41 in the nonclipped and 2.18 +/- 0.23 in the clipped kidneys (P less than 0.001). The pressure distal to the clip was 104 +/- 7 mmHg. The renal vascular resistance (RVR) (in mmHg X ml-1 X min-1 X g-1) was 25.0 +/- 1.4 in the control kidneys vs. 58.4 +/- 4.5 in the nonclipped (P less than 0.001) and 39.9 +/- 6.6 in the clipped kidneys (P less than 0.01). The RBF autoregulation was well preserved in the nonclipped kidneys but reset to a higher lower pressure limit of autoregulation of 106 +/- 4 mmHg, which was significantly higher than in the normotensive controls (84 +/- 6 mmHg) (P less than 0.01). In the clipped kidneys there was complete loss of RBF autoregulation. RSR decreased with reduction of the perfusion pressure in the clipped kidneys. The increased RVR might have been due to a combination of structural and functional changes in both kidneys.

Interaction between epinephrine and renal nerves in control of renin secretion rate.

To determine whether the increase in renin secretion rate (RSR) produced by the beta 2-adrenoceptor agonist epinephrine was dependent on intact renal innervation, epinephrine (10 ng X kg-1 X min-1) was infused bilaterally into an innervated and a denervated kidney (ira) of the same anesthetized dog at spontaneous and reduced renal arterial pressure (decreases RAP, 100 mmHg). Epinephrine ira did not affect mean arterial pressure, renal hemodynamics, or urinary sodium excretion of either kidney. At spontaneous RAP epinephrine ira increased RSR from 633 +/- 134 to 926 +/- 137 ng/min in innervated kidneys but did not change RSR in denervated kidneys. decreases RAP in the presence of epinephrine ira resulted in an increase in RSR from 969 +/- 248 to 2,564 +/- 630 ng/min in innervated kidneys, which was greater than that produced in the absence of epinephrine, from 741 +/- 244 to 1,606 +/- 431 ng/min. In denervated kidneys decreases RAP resulted in similar increases in RSR in the absence and presence of epinephrine ira from 41 +/- 15 to 166 +/- 60 ng/min and from 59 +/- 210 to 235 +/- 78 ng/min, respectively. These results demonstrate that the increase in RSR produced by epinephrine is dependent on intact renal innervation at spontaneous and decreases RAP and suggest that epinephrine increases RSR by a prejunctional mechanism. The beta 1-adrenoceptor antagonist metoprolol (0.3-0.5 microgram X kg-1 X min-1 ira) abolished the enhanced RSR response to decreases RAP produced by epinephrine ira. Similarly, the beta 2-adrenoceptor antagonist ICI 118551 (0.005-0.25 microgram X kg-1 X min-1 ira) abolished the enhanced RSR response to decreases RAP produced by epinephrine.(ABSTRACT TRUNCATED AT 250 WORDS)