Stimulation of renin secretion by NO donors is related to the cAMP pathway

Kurtz, Armin; Götz, K.H.; Hamann, Marlies; Kieninger, Martin; Wagner, Charlotte

doi:10.1152/ajprenal.1998.274.4.f709

Cited by 19 publications

(33 citation statements)

References 22 publications

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“…Thus we conclude that the strong attenuation of loop diuretic-stimulated renin release by L-NAME in isolated, perfused kidneys from wild-type, nNOS, and eNOS knockout mice is probably due to a direct effect of NO removal from the JG cell environment. Inhibition of basal and loop diuretic-induced renin secretion by L-NAME has previously also been demonstrated in the isolated, perfused rat kidney (11,25). Furthermore, NOS inhibition abolished the increase in renin release caused by furosemide pretreatment in dissected rat renal microvessels (6).…”

Section: Discussionmentioning

confidence: 65%

Permissive role of nitric oxide in macula densa control of renin secretion

Castrop

Schweda²,

Mizel³

et al. 2004

American Journal of Physiology-Renal Physiology

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Experiments were performed in neuronal (nNOS)-and endothelial nitric oxide synthase (eNOS)-deficient mice to study the role of nitric oxide (NO) in macula densa control of renin secretion in vivo and in the isolated, perfused mouse kidney. Acute and chronic administration of loop diuretics was used as a method to stimulate macula densa-mediated renin secretion. Increases in plasma renin concentration (PRC) in response to a 3-day infusion of bumetanide (50 mg⅐kg Ϫ1 ⅐day Ϫ1 ) or an acute injection of furosemide (50 mg/kg ip) were not markedly altered in nNOSϪ/Ϫ mice. Responses to furosemide were also maintained in eNOSϪ/Ϫ mice, but the administration of N -nitro-L-arginine methyl ester (L-NAME) markedly attenuated the PRC response to furosemide in these mice. In the isolated kidney preparation, bumetanide caused similar relative increases in renin secretion in kidneys of wild-type, nNOSϪ/Ϫ, and eNOSϪ/Ϫ mice. Bumetanide only marginally increased renin secretion in L-NAME-treated kidneys, but the bumetanide effect was normalized by S-nitroso-N-acetyl-penicillamine. Basal PRC was significantly reduced in male nNOSϪ/Ϫ mice compared with nNOSϩ/ϩ (189 Ϯ 28 vs. 355 Ϯ 57 ng ANG I ⅐ml Ϫ1 ⅐h Ϫ1 ; P ϭ 0.017). There was no significant difference in PRC between eNOSϩ/ϩ and eNOSϪ/Ϫ mice. Basal renin secretion rates in perfused kidneys isolated from nNOSϪ/Ϫ or eNOSϪ/Ϫ mice were markedly reduced compared with wild-type controls. Our data suggest that NO generated by macula densa nNOS does not play a specific mediator role in macula densa-dependent renin secretion. However, NO independent of its exact source permits the macula densa pathway of renin secretion to function normally. plasma renin; isolated, perfused kidney; neuronal nitric oxide synthase knockout; endothelial nitric oxide synthase knockout; furosemide; bumetanide THE MACULA DENSA (MD) CELLS LOCATED at the terminal end of the loop of Henle are believed to play an important role in both the regulation of preglomerular resistance and the control of renin secretion. Commensurate with their distinct function as sensor cells in these local regulatory pathways, MD cells have a number of unique characteristics that distinguish them from neighboring cells of the cortical thick ascending limb. One of the more striking of these discriminating features is the expression of substantial amounts of neuronal nitric oxide synthase (nNOS) and the ability to generate nitric oxide (NO) (31, 53).A considerable body of experimental evidence indicates that the expression of nNOS in the MD and the expression and secretion of renin by juxtaglomerular (JG) granular cells are altered in parallel by a variety of interventions. Reductions in oral salt intake (4,42,46, 50), renal hypoperfusion, and pharmacological blockade of Na-K-2Cl cotransport of the thick ascending limb (4, 43) all stimulate the expression of both proteins. Furthermore, changes in NOS activity have been demonstrated to affect renin secretion, and the majority of studies suggest a stimulatory role for NO (4,20,35,40,42). It ha...

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Section: Discussionmentioning

confidence: 65%

Permissive role of nitric oxide in macula densa control of renin secretion

Castrop

Schweda²,

Mizel³

et al. 2004

American Journal of Physiology-Renal Physiology

Self Cite

View full text Add to dashboard Cite

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“…2), it appears as if the inhibitory pathway could be masked by high cAMP efficacy. Conversely, in experiments with isolated perfused kidneys, NO donors have been shown to exert an intensified inhibitory effect on renin secretion in presence of calcium-mobilizing factors such as angiotensin II (30), suggesting that states of enhanced cytosolic calcium and protein kinase C activity impair the renin secretion via cAMP pathway. Taken together, it appears as if the momentary efficacy of cAMP or calcium and protein kinase C systems determines whether the stimulatory or the inhibitory pathway predominates, thus, controlling the overall effect of cGMP on the renin system.…”

Section: Discussionmentioning

confidence: 97%

“…Male Sprague-Dawley rats (250-300 g body weight; Indianapolis, IN) having free access to commercial pellet chow and tap water were obtained from the local animal house and used throughout. Preparation and kidney perfusion were performed in a recycling system as described in detail previously (30). After establishing the reperfusion loop, perfusate flow rates usually stabilized within 15 min.…”

Section: Methodsmentioning

confidence: 99%

“…Similar contradictory data-stimulation (22-24) and inhibition (25)(26)(27)(28) of renin secretion-have been obtained for atrial natriuretic peptide. The data from studies on the effects of stable, membrane-permeable cGMP analogues is more consistent and generally reflect inhibition of renin secretion from isolated perfused kidneys, kidney slices, or isolated JG cells (18,27,(29)(30)(31)(32). Inhibition of renin secretion by cGMP could, in principle, be mediated by three different cGMP receptors: the cGMP-dependent protein kinases (cGKs), cGMPgated ion channels, or cGMP-regulated phosphodiesterases (33)(34)(35)(36).…”

Section: Introductionmentioning

confidence: 97%

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Role of cGMP-kinase II in the control of renin secretion and renin expression.

Wagner¹,

Pfeifer²,

Ruth³

et al. 1998

J. Clin. Invest.

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To investigate the roles of the cGMP-dependent protein kinases (cGKs) in the control of the renin system, we studied the regulation of renin in cGKI-or cGKII-deficient mice in vivo and in vitro. Renal renin mRNA levels both under stimulatory (low-salt diet plus ramipril) and inhibitory (high-salt diet) conditions were not different between wildtype and cGKI Ϫ / Ϫ mice, but were significantly elevated in cGKII Ϫ / Ϫ mice under all experimental conditions. In primary cultures of renal juxtaglomerular cells (JG) established from wild-type, cGKI Ϫ / Ϫ , and cGKII Ϫ / Ϫ mice, the adenylate cyclase activator forskolin stimulated renin secretion similarly in all genotypes tested. 8-bromo-cGMP attenuated basal and forskolin-stimulated renin secretion in cultures from wild-type and cGKI Ϫ / Ϫ , but had no effect in cells isolated from cGKII Ϫ / Ϫ mice. Activation of cGKs by 8-bromo-cGMP decreased renin secretion from the isolated perfused rat kidney, independent of prestimulation by ␤ -adrenoreceptor activation, macula densa inhibition, reduced perfusion pressure, or by a nominally calcium-free perfusate. Taken together, these findings suggest that activation of cGKII has a general inhibitory effect on renin secretion from renal JG cells. ( J. Clin. Invest. 1998. 102:1576-1582.)

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“…33 This action would be magnified by the effect of NO to inhibit phosphodiesterase 3 and thereby to stabilize cAMP. 34,35 Finally, angiotensin II removal is usually associated with a decrease of MAP and reflex activation of the sympathetic nervous system. That the effect of both of these changes are mediated by ligands that signal through Gs␣ is supported by our previous finding that the effects of a BP reduction by hydralazine and of the ␤-adrenergic agonist isoproterenol on plasma renin are drastically curtailed in Gs␣-deficient mice.…”

Section: Discussionmentioning

confidence: 99%

Stimulation of Renin Secretion by Angiotensin II Blockade is Gsα-Dependent

Chen

Kim²,

Eisner³

et al. 2010

Journal of the American Society of Nephrology

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Angiotensin II converting enzyme inhibitors (ACEI) or angiotensin II receptor blockers (ARB) presumably stimulate renin secretion by interrupting angiotensin II feedback inhibition. The increase in cytosolic calcium caused by activation of Gq-coupled AT1 receptors may mediate the renin-inhibitory effect of angiotensin II at the cellular level, implying that ACEI and ARB may work by reducing intracellular calcium. Here, we investigated whether angiotensin II blockade acts predominantly through Gs-mediated stimulation of adenylyl cyclase (AC) by testing the effect of ACEI and ARB in mice with juxtaglomerular cell-specific deficiency of the AC-stimulatory Gs␣. The ACEI captopril and quinaprilate and the ARB candesartan significantly increased plasma renin concentration (PRC) to 20 to 40 times basal PRC in wild-type mice but did not significantly alter PRC in Gs␣-deficient mice. Captopril also completely abrogated renin stimulation in wild-type mice after co-administration of propranolol, indomethacin, and L-NAME. Treatment with enalapril and a low-NaCl diet for 7 days led to a 35-fold increase in PRC among wild-type mice but no significant change in PRC among Gs␣-deficient mice. Three different pharmacologic inhibitors of AC reduced the stimulatory effect of captopril by 70% to 80%. In conclusion, blockade of angiotensin II stimulates renin synthesis and release indirectly through the action of ligands that activate the cAMP/PKA pathway in a Gs␣-dependent fashion, including catecholamines, prostaglandins, and nitric oxide. 21: 986 -992, 201021: 986 -992, . doi: 10.1681 Angiotensin II regulates renin secretion through a homeostatic mechanism that has been called the "short feedback loop," with renin synthesis and secretion inhibited by increases and stimulated by reductions of angiotensin II concentration. 1 The cellular mechanisms underlying the feedback effects of angiotensin II are not entirely clear. There is good experimental support for the notion that the acute inhibition is mediated, at least in part, by a direct type 1 angiotensin II receptor (AT 1A )-dependent effect of the peptide on cell calcium. 1,2 Angiotensin II inhibits renin release in kidney slices 3 and in isolated juxtaglomerular granular (JG) cells, where the effect is blocked by losartan. 4,5 In the isolated JG cell, angiotensin II increases intracellular calcium levels, with increases correlating with the reduction of renin release. 5 On the other hand, it is unclear whether the stimulatory arm of the short feedback loop (i.e., the increase of renin in response to a reduction of angiotensin II) can be explained by the reverse of the J Am Soc Nephrol

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Stimulation of renin secretion by NO donors is related to the cAMP pathway

Cited by 19 publications

References 22 publications

Permissive role of nitric oxide in macula densa control of renin secretion

Permissive role of nitric oxide in macula densa control of renin secretion

Role of cGMP-kinase II in the control of renin secretion and renin expression.

Stimulation of Renin Secretion by Angiotensin II Blockade is Gsα-Dependent

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