Modulation of angiotensin‐converting enzyme by nitric oxide

Ackermann, A.; Fernández-Alfonso, Marı́a S.; Rojas, Romina; Ortega, T.; Paul, M; González, Carmen

doi:10.1038/sj.bjp.0701836

Cited by 95 publications

(55 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…ACE expression or activity is increased when eNOS expression or activity is decreased (21,22). There are, however, very few data available regarding the effect of AT1 blockers (1) and to our knowledge, no data exist regarding ACE inhibitors on the expression /activity of nNOS.…”

Section: Discussionmentioning

confidence: 86%

Angiotensin-Converting Enzyme Inhibitors and AT1-Receptor Antagonist Restore Nitric Oxide Synthase (NOS) Activity and Neuronal NOS Expression in the Adrenal Glands of Spontaneously Hypertensive Rats

Qadri

Arens

Schwartz

et al. 2001

Japanese Journal of Pharmacology

View full text Add to dashboard Cite

ABSTRACT-During development of hypertension in spontaneously hypertensive (SHR) rats, the activity of adrenal nitric oxide synthase (NOS) was investigated. SHR and Wistar-Kyoto (WKY) rats were studied at different ages: 3 -4, 7 -8 and 12 -13 weeks after birth. Basal NOS activity was measured by the ability of homogenate to convertAt all ages, SHR rats exhibited 50 -60% reduction in NOS activity when compared to age-matched WKY rats. In a following study, SHR rats (12 -13 weeks) were treated chronically with the angiotensin I-converting enzyme inhibitors (ACE-I) captopril or enalapril, or the AT1-receptor antagonist losartan (2´25, 10 and 60 mg/kg per day for 10 days, respectively). The total NOS activity and protein expression of NOS isoenzymes from adrenals were determined. The basal NOS activity and protein expression of neuronal NOS (nNOS) was significantly increased in treated SHR rats when compared to control rats. The isoforms endothelial NOS and inducible NOS were undetectable. We conclude that impaired NO synthesis in the adrenal glands of SHR rats may contribute to the onset and maintenance of hypertension. The upregulation of nNOS protein in the adrenal glands may be one of the mechanisms by which ACE inhibitors and AT1-receptor antagonists by restoring the NO synthesis, mediate their antihypertensive effects.Keywords: Nitric oxide synthase, Spontaneously hypertensive rat, Adrenal gland, Angiotensin-converting enzyme inhibitor, LosartanNeuronal nitric oxide synthase (nNOS) has been localized immunohistochemically in different central and peripheral organs including the medulla of rat adrenal glands (1 -3). Considerable evidence demonstrates that nonneuronal mediators such as endothelin-1, prostaglandins or NO modulate sympathetic neurotransmission. Recently, it has been reported that chromaffin cells isolated from bovine adrenals possess an autocrine NO /cGMP pathway tonically controlling the release of catecholamines (4). This was further supported by the fact that in isolated and perfused canine adrenal glands treatment with N G -monomethyl-L-arginine, an inhibitor of NOS, increased the basal efflux of noradrenaline, adrenaline and dopamine, whereas the effects of N G -monomethyl-L-arginine were reversed in the presence of L-arginine, the substrate of NOS (5). Therefore, it has been suggested that constitutive synthesis of NO within the adrenal medulla may modulate the release of catecholamines into the circulation, thereby playing an important role in the maintenance of blood pressure (BP) at physiological levels. We therefore hypothesized that an impaired synthesis of NO within the adrenal medulla in spontaneously hypertensive (SHR) rats may be one of the crucial factors contributing to the development and maintenance of hypertension. Furthermore, the reduction in BP following treatment with angiotensin-converting enzyme inhibitors (ACE-I) or AT1-receptor antagonists may affect the NO production within the adrenal gland. In the present study, we investigated the activities of NOS with respect to di...

show abstract

Section: Discussionmentioning

confidence: 86%

Angiotensin-Converting Enzyme Inhibitors and AT1-Receptor Antagonist Restore Nitric Oxide Synthase (NOS) Activity and Neuronal NOS Expression in the Adrenal Glands of Spontaneously Hypertensive Rats

Qadri

Arens

Schwartz

et al. 2001

Japanese Journal of Pharmacology

View full text Add to dashboard Cite

show abstract

“…The actions of NO to reduce blood pressure during pregnancy are pleiotropic, primarily through endothelium-dependent dilation and resulting smooth muscle relaxation, which decreases vascular resistance. NO also negatively regulates the activity of many vasopressors, including endothelin-1 and Ang II (49)(50)(51), and is antithrombotic (52). Our study and others, including in vivo studies of pregnant eNOS mutant mice and rodents given l-NAME during pregnancy, provide valuable experimental evidence that inhibition of NO during pregnancy induces hypertension, similar to preeclampsia (34,36,50,53,54).…”

Section: Discussionmentioning

confidence: 99%

Soluble fms-like tyrosine kinase 1 promotes angiotensin II sensitivity in preeclampsia

Burke¹,

Zsengellér²,

Khankin³

et al. 2016

Journal of Clinical Investigation

126

101

View full text Add to dashboard Cite

“…Angiotensin I vasoconstriction curves were assessed in rings not submitted to DEA NONOate, as NO-releasing compounds could interfere with ACE activity. 30 …”

Section: Vascular Reactivity Studiesmentioning

confidence: 99%

Mineralocorticoid Receptor Blockade Improves Vasomotor Dysfunction and Vascular Oxidative Stress Early After Myocardial Infarction

Sartório

Fraccarollo²,

Galuppo³

et al. 2007

Hypertension

View full text Add to dashboard Cite

Abstract-Mineralocorticoid receptor blockade improves mortality early after myocardial infarction (MI). This study investigated the vascular effects of mineralocorticoid receptor blockade in the early phase postinfarction in rats. Starting immediately after coronary ligation, male Wistar rats were treated with placebo or eplerenone (100 mg/kg/d). After 7 days, hemodynamic assessment was performed and endothelial function was determined. Maximum acetylcholineinduced relaxation was significantly attenuated in aortic rings from rats with heart failure after MI, and ameliorated by eplerenone treatment. Endothelium-independent relaxation by DEA-NONOate was similar among the groups. Endothelial NO synthase phosphorylation was reduced in the aorta of MI rats and restored by eplerenone therapy. Angiotensin I-induced vasoconstriction as well as angiotensin-converting enzyme protein levels were enhanced in aortas from MI placebo rats, and reduced by mineralocorticoid receptor inhibition. Aortic reactive oxygen species formation as well as the expression of the NAD(P)H oxidase subunit p22 phox were increased after MI and normalized in eplerenone treated rats. In conclusion, mineralocorticoid receptor antagonism improved endothelial dysfunction in the early phase post-MI. Underlying mechanisms involve inhibition of vascular angiotensin-converting enzyme upregulation and improvement of endothelial NO synthase-derived NO bioavailability. Key Words: aldosterone Ⅲ acute myocardial infarction Ⅲ endothelial dysfunction Ⅲ oxidative stress C hronic heart failure is accompanied by endothelial dysfunction. 1 Increased production of vascular reactive oxygen species, especially superoxide anion (O 2 Ϫ ), as well as diminished antioxidant defense in heart failure contribute to a reduced bioavailability of NO. 2 The renin angiotensin aldosterone system (RAAS) is markedly activated and displays a central role in heart failure progression. 3,4 Aldosterone synthesis and mineralocorticoid receptors (MR) have been described in the vascular wall. 5,6 Aldosterone stimulates vascular ACE expression/activity and potentiates angiotensin II effects. 7-10 Angiotensin II and aldosterone stimulate vascular O 2 Ϫ production, promoting NO scavenging and reducing its bioavailability. [11][12][13] In healthy subjects, contradictory effects of aldosterone on endothelial function are reported. Farquharson et al 14 showed that intravenous infusion of aldosterone reduced the forearm blood flow response to acetylcholine but did not affect sodium nitroprusside-induced vasodilation, thus inducing acute endothelial dysfunction. Others reported that aldosterone increases forearm blood flow and induces vasodilatation by stimulating NO release through rapid nongenomic effects. 15 In a recent investigation, short-term and chronic aldosterone excess did not affect forearm blood flow, but enhanced the vasodilator response to exogenous NO and improved endothelium-dependent NO-mediated vasodilation in the forearm vasculature of healthy men. 16,17 However, in subjects wit...

show abstract

Modulation of angiotensin‐converting enzyme by nitric oxide

Cited by 95 publications

References 32 publications

Angiotensin-Converting Enzyme Inhibitors and AT1-Receptor Antagonist Restore Nitric Oxide Synthase (NOS) Activity and Neuronal NOS Expression in the Adrenal Glands of Spontaneously Hypertensive Rats

Angiotensin-Converting Enzyme Inhibitors and AT1-Receptor Antagonist Restore Nitric Oxide Synthase (NOS) Activity and Neuronal NOS Expression in the Adrenal Glands of Spontaneously Hypertensive Rats

Soluble fms-like tyrosine kinase 1 promotes angiotensin II sensitivity in preeclampsia

Mineralocorticoid Receptor Blockade Improves Vasomotor Dysfunction and Vascular Oxidative Stress Early After Myocardial Infarction

Contact Info

Product

Resources

About