Renin release in rats during blockade of nitric oxide synthesis

Johnson, Robert A.; Freeman, R. H.

doi:10.1152/ajpregu.1994.266.6.r1723

Cited by 43 publications

(26 citation statements)

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“…4), however, does not suggest that the increase of blood pressure was the singular mechanism by which NOS inhibition blunted the increase of renin mRNA levels in response to losartan and ramipril. This hypothesis is supported by recent findings of Johnson and Freeman (41), who demonstrated that the NOinduced stimulation of the renin system is independent of blood pressure changes. Moreover, inhibition of NOS activity also inhibits the renin system in isolated rat kidneys in which the perfusion pressure is kept constant (18,19,21,24).…”

Section: Discussionsupporting

confidence: 75%

Tonic stimulation of renin gene expression by nitric oxide is counteracted by tonic inhibition through angiotensin II.

Schricker

Hegyi

Hamann

et al. 1995

Proc. Natl. Acad. Sci. U.S.A.

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This study was designed to examine the possible involvement of prostaglandins and nitric oxide (NO) in the renin stimulatory effect ofangiotensin 11 (AngII) antagonists. To this end, plasma renin activities (PRAs) and renal renin mRNA levels were assayed in rats that were treated with the Angconverting enzyme inhibitor ramipril or with the AnglI AT1-receptor antagonist losartan. Ramipril and losartan increased PRA values from 7.5 + 1.6 to 86 ± 6 and 78 ± 22 ng of AngI per h per ml and renin mRNA levels from 112 ± 9% to 391 + 20%o and 317 ± 10%o, respectively. Inhibition of prostaglandin formation with indomethacin did not influence basal or ramiprilaffected PRA. Basal renin mRNA levels also were unchanged by indomethacin, while increases in renin mRNA levels after ramipril treatment were slightly reduced by indomethacin. Inhibition of NO synthase by nitro-L-arginine methyl ester (L-NAME) reduced PRA values to 3.2 ± 0.9, 34 ± 13, and 12.1 ± 2.7 ng of AngI per h per ml in control, ramipril-treated, and losartan-treated animals, respectively. Renin mRNA levels were reduced to 77 + 14% under basal conditions and ramipril-and losartan-induced increases in renin mRNA levels were completely blunted after addition of L-NAME. The AngIH antagonists, furthermore, induced an upstream recruitment of reninexpressing cells in the renal afferent arterioles, which was also blunted by L-NAME. These findings suggest that renin mRNA levels are tonically increased by NO and that the action of NO is counteracted by AngII.One of the most prominent in vivo effects of angiotensin (Ang)-converting enzyme (ACE) inhibitors is a marked stimulation of renin secretion and renin gene expression in the kidneys (1-5). Since ANGII is known as a negative feedback regulator of renin secretion and of renin gene expression (6, 7), it is thought that the renin stimulatory effects of ACE inhibitors are related to the inhibition of AnglI formation and consequently to the lowering of circulating and tissue AnglI levels (8).There is evidence that several in vivo effects of ACE inhibitors are not, as originally thought, due to the inhibition of AnglI formation but to the inhibition of kinin degradation (9-12). Inhibition of kinin degradation results in elevated tissue levels of autacoids such as prostaglandins and nitric oxide (NO), the formation of which is stimulated by kinins (11)(12)(13)(14). Although NO is reported to inhibit the renin system (15-17), contradictory findings suggest that NO stimulates the renin system (18-25) and also that prostaglandins stimulate the renin system (for review, see ref. 26). With such a stimulatory effect of NO and prostaglandins on the renin system, it is possible that the renin stimulatory effect of ACE inhibitors could be related to an enhanced formation of prostaglandins and NO.To investigate the mode of action of ACE inhibitors on the renin system, we studied renin release and renin mRNA levels in the kidneys of conscious rats that were treated with the ACE inhibitor ramipril (27) or with the Angll AT1-rec...

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Section: Discussionsupporting

confidence: 75%

Tonic stimulation of renin gene expression by nitric oxide is counteracted by tonic inhibition through angiotensin II.

Schricker

Hegyi

Hamann

et al. 1995

Proc. Natl. Acad. Sci. U.S.A.

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“…However, with all of the relevant data taken together, it now appears well established that the overall effect of NO on renin secretion, at least as far as the in vivo situation is concerned, is stimulatory (407,683,765,770).…”

Section: Nomentioning

confidence: 99%

Physiology of Kidney Renin

Castrop

Höcherl

Kurtz

et al. 2010

Physiological Reviews

232

277

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The protease renin is the key enzyme of the renin-angiotensin-aldosterone cascade, which is relevant under both physiological and pathophysiological settings. The kidney is the only organ capable of releasing enzymatically active renin. Although the characteristic juxtaglomerular position is the best known site of renin generation, renin-producing cells in the kidney can vary in number and localization. (Pro)renin gene transcription in these cells is controlled by a number of transcription factors, among which CREB is the best characterized. Pro-renin is stored in vesicles, activated to renin, and then released upon demand. The release of renin is under the control of the cAMP (stimulatory) and Ca2+(inhibitory) signaling pathways. Meanwhile, a great number of intrarenally generated or systemically acting factors have been identified that control the renin secretion directly at the level of renin-producing cells, by activating either of the signaling pathways mentioned above. The broad spectrum of biological actions of (pro)renin is mediated by receptors for (pro)renin, angiotensin II and angiotensin-( 1 – 7 ).

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“…First, L-NAME-induced hypertension suppresses plasma renin, eliminating the confounding effects of circulating angiotensin II. 10,11 Second, previous reports indicate that L-NAME treatment activates the renal RAS. 12 Third, we reasoned it would be important to evaluate the role of the renal ACE/angiotensin II Figure 1.…”

mentioning

confidence: 99%

Renal Angiotensin-Converting Enzyme Is Essential for the Hypertension Induced by Nitric Oxide Synthesis Inhibition

Giani

Janjulia

Kamat

et al. 2014

Journal of the American Society of Nephrology

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The kidney is an important source of angiotensin-converting enzyme (ACE) in many species, including humans. However, the specific effects of local ACE on renal function and, by extension, BP control are not completely understood. We previously showed that mice lacking renal ACE, are resistant to the hypertension induced by angiotensin II infusion. Here, we examined the responses of these mice to the low-systemic angiotensin II hypertensive model of nitric oxide synthesis inhibition with L-NAME. In contrast to wild-type mice, mice without renal ACE did not develop hypertension, had lower renal angiotensin II levels, and enhanced natriuresis in response to L-NAME. During L-NAME treatment, the absence of renal ACE was associated with blunted GFR responses; greater reductions in abundance of proximal tubule Na + /H + exchanger 3, Na + /Pi co-transporter 2, phosphorylated Na + /K + /Cl 2 cotransporter, and phosphorylated Na + /Cl 2 cotransporter; and greater reductions in abundance and processing of the g isoform of the epithelial Na + channel. In summary, the presence of ACE in renal tissue facilitates angiotensin II accumulation, GFR reductions, and changes in the expression levels and post-translational modification of sodium transporters that are obligatory for sodium retention and hypertension in response to nitric oxide synthesis inhibition.

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Renin release in rats during blockade of nitric oxide synthesis

Cited by 43 publications

References 0 publications

Tonic stimulation of renin gene expression by nitric oxide is counteracted by tonic inhibition through angiotensin II.

Tonic stimulation of renin gene expression by nitric oxide is counteracted by tonic inhibition through angiotensin II.

Physiology of Kidney Renin

Renal Angiotensin-Converting Enzyme Is Essential for the Hypertension Induced by Nitric Oxide Synthesis Inhibition

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