Vascular relaxation and cGMP in hypertension

Otsuka, Yuji; DiPiero, Albert; E, Hirt; Brennaman, B; Lockette, Warren

doi:10.1152/ajpheart.1988.254.1.h163

Cited by 39 publications

(29 citation statements)

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“…In experimentally induced hypertension, the attenuated increase in cGMP in response to acetylcholine could be reversed by restoring the blood pressure to normal. 30 Therefore, in our study the correction of hypertension by antihypertensive treatment also may have corrected hypertension-induced changes in vascular cGMP content. However, our results clearly demonstrate that low-dose ACE inhibitor treatment led to an increase in aortic cGMP level without affecting blood pressure.…”

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confidence: 54%

Long-term low-dose angiotensin converting enzyme inhibitor treatment increases vascular cyclic guanosine 3',5'-monophosphate.

et al. 1993

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We investigated functional changes in aortic preparations of spontaneously hypertensive rats treated in utero and subsequently up to 20 weeks of age with the angiotensin converting enzyme (ACE) inhibitors ramipril (0.01 and 1 mg/kg per day) and perindopril (0.01 nig/kg per day). Early-onset treatment with the high dose of ramipril inhibited aortic ACE activity, prevented the development of hypertension, increased aortic vasodilator responses to acetylcholine (10~8 to 10~6 mol/L), decreased vasoconstrictor responses to norepinephrine (10~8 mol/L), and increased aortic cyclic GMP content by 160%. Low-dose ramipril inhibited aortic ACE activity and attenuated the aortic vasoconstrictor response to norepinephrine but had no effect on blood pressure. Low-dose treatment with ramipril and perindopril resulted in a significant increase in aortic cyclic GMP content by 98% and 77%, respectively. Long-term coadministration of the bradykinin B 2 -receptor antagonist Hoe 140 abolished the ACE inhibitor-induced increase in aortic cyclic GMP. Our data demonstrate that long-term treatment with ACE inhibitors can alter vascular function of compliance vessels independently of the antihypertensive action. The increase in aortic cyclic GMP was due to bradykinin potentiating the action of the ACE inhibitors. (Hypertension. 1993;22:682-687.) KEY WORDS • angiotensin converting enzyme inhibitors • guanosine cyclic monophosphate • perindopril • ramipril • rats, inbred SHR • bradykininS pontaneously hypertensive rats (SHR) and strokeprone SHR (SHRSP) develop hypertension during their first 12 weeks of life. The increase in blood pressure is associated with functional changes of the vascular wall. It has been reported that the endothelium-dependent relaxation of blood vessels to different agonists is impaired in hypertensive compared with normotensive animals.16 Endothelium-derived relaxing factor (EDRF) can be released by the endothelium in response to a number of agonists, including acetylcholine, bradykinin, and norepinephrine (for review, see References 7 and 8). EDRF causes vascular relaxation by stimulation of soluble guanylate cyclase, leading to a rise in the intracellular cyclic GMP (cGMP) content. The formation of cGMP in rabbit aortic segments and bovine endothelial cells can be stimulated in a concentration-dependent fashion by the angiotensin converting enzyme (ACE) inhibitor ramipril.9 This effect may be the result of an ACE inhibitor-induced potentiation of endogenous kinins, leading to enhanced EDRF release and, subsequently, cGMP formation.

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confidence: 54%

Long-term low-dose angiotensin converting enzyme inhibitor treatment increases vascular cyclic guanosine 3',5'-monophosphate.

et al. 1993

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“…This has not been investigated in the present study. However, there is evidence to suggest that NP may relax vascular smooth muscle through both guanosine 3':5'-cyclic monophosphate (cyclic GMP)-dependent and cyclic GMP-independent pathways (Otsuka et al, 1988). A component of the relaxant effect of glyceryltrinitrate may also be mediated by a mechanism which does not involve elevated cyclic GMP levels (Diamond & Chu, 1983).…”

Section: Suppression Of Endogenous Edrf Production Did Not Occur Durimentioning

confidence: 99%

Iron‐sulphur cluster nitrosyls, a novel class of nitric oxide generator: mechanism of vasodilator action on rat isolated tail artery

Flitney

Megson

Flitney

et al. 1992

British J Pharmacology

110

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“…Several groups have reported reduced endothelium-dependent vascular responses (5)(6)(7)(8), whereas other workers have reported no change (9) or an increase (10) in endothelium-dependent relaxation in arteries from hypertensive animals. Reduced endothelium-dependent vascular relaxation has also been reported in heart failure (1 [1][2][3][4][5][6][7][8][9][10][11][12][13] and in the presence of atherosclerotic lesions (14)(15)(16). Endotheliumderived relaxing factor (EDRF),' which appears to be nitric oxide (NO), seems to be an ideal modulator oflocal blood flow, because stimulation of its release integrates both mechanical signals (shear stress) and hormonal signals (acetylcholine, bradykinin, etc.)…”

Section: Introductionmentioning

confidence: 99%

Determinants of aortic cyclic guanosine monophosphate in hypertension induced by chronic inhibition of nitric oxide synthase.

Arnal¹,

Warin²,

Michel³

1992

J. Clin. Invest.

246

128

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Nitric oxide (NO) and atrial natriuretic factor (ANF) cause vascular relaxation by generating cyclic guanosine monophosphate (cGMP) via activation of the soluble and particulate guanylate cyclases, respectively. The chronic effects of N-nitro-L-arginine methyl ester (L-NAME), an L-arginine antagonist and NO synthase inhibitor, on the blood pressure and plasma and aortic cGMP levels of rats were tested. Wistar rats (n = 10 per group) were given doses ofL-NAME (0, 1, 5, 10, 20, 50, and 100 mg/kg . d) by gavage twice a day for 4 wk. Chronic L-NAME induced a time-and dose-dependent increase in blood pressure. The total heart weight/body weight ratio did not change in any group, despite the hypertension. The plasma levels ofcGMP did not change significantly in any group, and were correlated with the plasma ANF levels (r = 0.51, P < 0.0001). Aortic cGMP decreased in negative correlation with increasing L-NAME from 0 to 10 mg/kg . d, culminating in a 10-fold drop arterial wall cGMP. The aortic cGMP content of rats in the four highest dose groups (from 10 to 100 mg/d) tended to increase slightly and was positively correlated with endogenous ANF (r = 0.48, P < 0.002, n = 40). Intravenous L-arginine decreased arterial blood pressure and reversed the decline in aortic cGMP. Exogenous ANF and sodium nitroprusside both significantly increased aortic cGMP. Neither the arterial wall concentrations of cGMP-dependent kinase nor cAMP was changed by L-NAME. Thus, chronic blockade of NO synthase with L-NAME induces a dose-dependent increase in blood pressure and decrease in aortic cGMP. The in vivo basal aortic cGMP seems to be mainly dependent on NO synthase: soluble guanylate cyclase activity and to a minor extent on particulate guanylate cyclase activity. (J. Clin. Invest. 1992.90:647-652.)

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Vascular relaxation and cGMP in hypertension

Cited by 39 publications

References 0 publications

Long-term low-dose angiotensin converting enzyme inhibitor treatment increases vascular cyclic guanosine 3',5'-monophosphate.

Long-term low-dose angiotensin converting enzyme inhibitor treatment increases vascular cyclic guanosine 3',5'-monophosphate.

Iron‐sulphur cluster nitrosyls, a novel class of nitric oxide generator: mechanism of vasodilator action on rat isolated tail artery

Determinants of aortic cyclic guanosine monophosphate in hypertension induced by chronic inhibition of nitric oxide synthase.

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