Amlodipine Releases Nitric Oxide From Canine Coronary Microvessels

Ovid Technologies (Wolters Kluwer Health) - Tập 97 Số 6 - Trang 576-580 - 1998
Xiaoping Zhang1, Thomas H. Hintze1
1From the Department of Physiology, New York Medical College, Valhalla, NY.

Tóm tắt

Background —Recent studies suggest that amlodipine may reduce mortality in patients with heart failure, especially those with dilated cardiomyopathy. In general, drugs that release NO, such as organic nitrates and ACE inhibitors, have been shown to be of substantial benefit in the treatment of heart failure. Methods and Results —We hypothesized that a portion of the beneficial actions of amlodipine may involve the release or action of NO. Coronary microvessels were isolated from the heart of normal dogs and incubated with increasing doses of the calcium channel blockers nifedipine, diltiazem, and amlodipine or the ACE inhibitors enalaprilat and ramiprilat. Neither nifedipine nor diltiazem increased nitrite production at any dose studied. In marked contrast, amlodipine caused a dose-dependent increase in nitrite production from 74±5 to 130±8 pmol/mg (by 85±21%,10 −5 mol/L, P <.05) that was similar in magnitude to that of either of the ACE inhibitors. Amlodipine also increased nitrite production in large coronary arteries and in aorta. N ω -Nitro- l -arginine methyl ester, HOE-140, and dichloroisocoumarin essentially abolished the increase in nitrite production, indicating that (1) nitrite production reflected NO formation, (2) nitrite production was dependent on stimulation of the kinin 2 receptor, and (3) nitrite production is most likely secondary to the formation of local kinins. Conclusions —Thus, unlike nifedipine and diltiazem, amlodipine releases NO from blood vessels.

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Tài liệu tham khảo

10.1161/circ.82.6.2242521

10.1161/circ.83.1.1984898

Littler WA, Sheridan DJ. Placebo-controlled trial of felodipine in patients with mild to moderate heart failure: UK Study Group. Br Heart J. 1995;71:428–433.

10.1016/0002-9149(68)90161-6

10.1056/NEJM199610103351504

10.1161/circ.95.1.176

Kichuk MR Zhang X Oz M Michler R Kaley G Nasjletti A Hintze TH. ACE inhibitors promote nitric oxide production in coronary microvessels from the failing explanted human heart. Am J Cardiol. In press.

10.1161/hyp.26.1.164

Vanhoutte PM, Boulanger CM, Illiano CS, Ngao T, Vidal M, Mombouli JV. Endothelium-dependent effects of converting enzyme inhibitors. J Cardiovasc Pharm. 1993;27:S10–S16.

Imura O, Shimamoto K. Role of kallikrein-kinin system in the hypotensive mechanisms of converting-enzyme inhibitors in essential hypertension. J Cardiovasc Pharmacol. 1989;13:S63–S66.

Moncada S, Palmer RMJ, Higgs EA. Nitric oxide, physiology, pathophysiology and pharmacology. Pharm Rev. 1991;43:109–142.

10.1007/BF01865514

10.1161/res.49.5.6794929

10.1161/circ.94.1.44

10.1161/res.74.2.7507417

10.1161/res.78.1.58

Winbury MM, Howe BB, Hefner MA. Effects of nitrates and other coronary dilators on large and small coronary vessels: an hypothesis for the mechanism of action of nitrates. J Pharmacol Exp Ther. 1969;168:70–95.

10.1161/circ.32.5.755

Vatner SF, Pagani M, Rutherford JD, Millard RW, WT Manders. Effects of nitroglycerin on cardiac function and regional blood flow distribution in conscious dogs. Am J Physiol. 1978;234:H244–H252.

Hintze TH Vatner SF. Comparison of the effects of nifedipine and nitroglycerin on large and small coronary arteries and cardiac function in conscious dogs. Circ Res. 1983;52(suppl I):I-139–I-146.

Murdoch D, Heel RC. Amlodipine: a review of its pharmacologic and pharmacokinetic properties and its therapeutic use in cardiovascular disease. Drugs. 1991;4:478–505.

Taylor SH. A review of amlodipine in myocardial ischemia. Postgrad Med J. 1991;67(suppl 5):S48–S51.

Magnon M, Gallix P, Cavero I. Intervessel (arteries and veins) and heart/vessel selectivities of therapeutically used calcium entry blockers: variable, vessel-dependent indexes. J Pharmacol Exp Ther. 1995;275:1157–1166.

10.1097/00004872-199603000-00017

Lyons D, Webster J, Benjamin N. The effect of antihypertensive therapy on responsiveness to local intra-arterial NG-monomethyl-l-arginine in patients with essential hypertension. J Hypertens. 1994;12:1047–1052.

10.1097/00005344-199510000-00013

Zhang X Xu X Forfia PR Nasjletti A Hintze TH. Neutral endopeptidase and angiotensin converting enzyme modulate nitric oxide via local kinin formation from canine coronary microvessels. Circulation. 1996;94(suppl I):I-61. Abstract.

10.1161/hyp.30.5.1105

10.1161/01.hyp.18.4.558

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Ovid Technologies (Wolters Kluwer Health)

Tập 97 Số 6

576-580

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