Neutral endopeptidase and angiotensin-converting enzyme inhibitors increase nitric oxide production in isolated canine coronary microvessels by a kinin-dependent mechanism

Journal of Cardiovascular Pharmacology
X ZhangT H Hintze

Abstract

Bradykinin is a substrate for both neutral endopeptidase 24.11 (NEP) and angiotensin-converting enzyme (ACE). Our previous studies showed that ACE inhibitors can stimulate nitric oxide production in coronary microvessels, which is mediated by local kinins. Whether inhibition of NEP also can affect local vascular NO production has not been established. To determine the role of NEP in the control of NO production, coronary microvessels were isolated from seven mongrel dogs. Two NEP inhibitors, phosphoramidon and thiorphan, and an ACE inhibitor, ramiprilat, were used. Nitrite, the metabolite of NO in aqueous solution, was measured by using the Griess reaction. Phosphoramidon and thiorphan (10(-6) M) increased nitrite production from 80 +/- 6 to 136 +/- 6 and 144 +/- 7 pmol/mg, respectively. Ramiprilat (10(-8) M) increased nitrite production from 78 +/- 6 to 155 +/- 7 pmol/mg wet weight. The effect of these agents on nitrite release was blocked by L-NAME, which inhibits NO synthase, HOE-140, which blocks bradykinin B2-receptor, and dichloroisocoumarin, which blocks kinin-forming enzymes. These results clearly indicate that inhibition of kinin metabolism by using neutral endopeptidase inhibitors increases NO production from coronary...Continue Reading

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Citations

Oct 4, 2000·The Annals of Thoracic Surgery·I KrassóiJ G Papp
Nov 9, 2000·European Journal of Pharmacology·K BagatéM Barthelmebs
Oct 12, 2000·Nihon rinsho. Japanese journal of clinical medicine·Y SaitoR Nagai
Mar 18, 2006·Journal of Human Hypertension·K A M Jandeleit-Dahm
Apr 14, 2004·Basic & Clinical Pharmacology & Toxicology·Qing-Xue ZhangDennis E Feierman
Dec 18, 2003·British Journal of Clinical Pharmacology·Matthew I WorthleyStephen G Worthley
Oct 9, 2014·Cardiovascular Pathology : the Official Journal of the Society for Cardiovascular Pathology·Marie Dennis LeoDinesh Kumar
Nov 27, 2002·Canadian Journal of Physiology and Pharmacology·Liliana RomanoMaría Peral de Bruno
Oct 5, 2018·Frontiers in Medicine·Duncan J Campbell
Nov 30, 2018·JAMA Cardiology·Kelsie E OatmenFrancis G Spinale
Jan 16, 2002·Journal of Cardiovascular Pharmacology·Xiao-Ping ZhangThomas H Hintze
Jul 7, 2000·Pharmacology & Therapeutics·T KomaruK Shirato

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