Plasma levels of nitric oxide and related vasoactive factors following long-term treatment with angiotensin-converting enzyme inhibitor in patients with essential hypertension

doi:10.1016/S0026-0495(99)90264-0

Metabolism

Volume 48, Issue 10, October 1999, Pages 1256-1259

https://doi.org/10.1016/S0026-0495(99)90264-0 Get rights and content

Abstract

Several mechanisms other than the inhibition of systemic and local formation of angiotensin II (Ang II) have been proposed to play a role in mediating the hypotensive effects of angiotensin-converting enzyme (ACE) inhibitors. In the present study, we measured plasma levels of nitric oxide (NO) and the related vasoactive factors bradykinin, 6-keto prostaglandin F_1α (6-keto PGF_1α) a stable metabolite of prostacyclin, and cyclic guanosine-3′,5′-monophosphate (cGMP) before and after a 4-week treatment with the ACE inhibitor lisinopril in 17 patients with essential hypertension. Plasma NO levels were measured by the Griess method after conversion of nitrate to nitrite. Long-term lisinopril treatment significantly reduced blood pressure and increased plasma NO and 6-keto PGF_1α. The treatment also tended to increase plasma levels of bradykinin and cGMP, but not to a significant extent. The posttreatment NO level was inversely correlated with posttreatment systolic, diastolic, and mean blood pressure (n = 17, r = −.68, P < .01, n = 17, r = −.54, P < .05, and n = 17, r = −.66, P < .01, respectively). The posttreatment bradykinin level was also modestly correlated with posttreatment systolic and mean blood pressure (n = 17, r = −.51, P < .05 and n = 17, r = −.55, P < .05, respectively). In contrast, posttreatment 6-keto PGF_1α and cGMP levels were not correlated with posttreatment systolic, diastolic, or mean blood pressure. These findings raise the possibility that increased formation of NO and bradykinin, as well as inhibition of the renin-angiotensin system, contribute to the hypotensive effect of the ACE inhibitor observed in our hypertensive patients.

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We investigated whether long-term treatment with the angiotensin-converting enzyme (ACE) inhibitor imidapril or the calcium channel antagonist nifedipine increases systemic nitric oxide (NO) production in patients with essential hypertension. Twenty-nine patients with essential hypertension were randomly divided into two groups, and they were treated with either imidapril or nifedipine once daily p.o. for 4 weeks. Long-term treatment with imidapril significantly decreased blood pressure and increased plasma NOx concentration. Long-term treatment with nifedipine also caused a comparable extent of significant decrease in blood pressure, but failed to alter plasma NOx levels. The imidapril treatment significantly inhibited serum ACE activity and increased plasma bradykinin concentration. Furthermore, the extent of inhibition of serum ACE activity and the extent of increase in plasma bradykinin concentration in response to the imidapril treatment were both significantly correlated with the extent of increase in plasma NOx concentration. In contrast, no such changes were noted after the nifedipine treatment. These results provide the first evidence that long-term treatment with imidapril enhances plasma NOx concentration in patients with essential hypertension. This effect does not seem to be due to the decrease in blood pressure. The increase in bradykinin concentration may be involved in the enhancing effect of the ACE inhibitor on NOx production in vivo.
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^☆: Supported by a Grant-in-Aid for Scientific Research from the Ministry of Education, Science and Culture of Japan.

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Plasma levels of nitric oxide and related vasoactive factors following long-term treatment with angiotensin-converting enzyme inhibitor in patients with essential hypertension☆

Abstract

Kidney Int

Neurosci Lett

J Mol Cell Cardiol

J Biol Chem

Am J Med

Am J Med

Converting enzyme inhibition in essential hypertension: The hypotensive response does not reflect only reduced angiotensin II formation

Hypertension

Measurement of circulating kinins, their changes by inhibition of kinase II and their possible blood pressure lowering effect

Agents Actions Suppl

Role of kallikrein-kinin system in the hypotensive mechanisms of converting enzyme inhibitors in essential hypertension

J Cardiovasc Pharmacol

Converting-enzyme inhibitor ramipril stimulates prostacyclin synthesis by isolated rat aorta: Evidence for a kinin-dependent mechanism

Klin Wochenschr

Kinin- and non-kinin-mediated interactions of converting-enzyme inhibitors with vasoactive hormones

J Cardiovasc Pharmacol

Ramiprilat enhances endothelial autacoid formation by inhibiting breakdown of endothelium-derived bradykinin

Hypertension