Coronary vascular nitric oxide activity in hypertension and hypercholesterolemia - Comparison of acetylcholine and substance P

被引:120
作者
Quyyumi, AA
Mulcahy, D
Andrews, NP
Husain, S
Panza, JA
Cannon, RO
机构
[1] National Institutes of Health, Cardiology Branch, NHLBI, Bethesda, MD
[2] National Institutes of Health, Cardiology Branch, NHLBI, Bethesda, MD 20892-1650
关键词
endothelium; hypercholesterolemia; acetylcholine; endothelium-derived factors; hypertension;
D O I
10.1161/01.CIR.95.1.104
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background Whether the abnormal responses of the human coronary circulation to acetylcholine in patients with hypertension and hypercholesterolemia extend to other, nonmuscarinic stimulators of the endothelium and whether this signifies a specific abnormality of NO is not known. Methods and Results We studied 26 patients with angiographically normal coronary arteries, 10 without risk factors, and 16 with either hypertension (n=9) and/or hypercholesterolemia (n=10). Dose-response curves were performed with acetylcholine, substance P, and sodium nitroprusside before and after N-G-monomethyl-L-arginine (L-NMMA). Substance P produced predominantly epicardial coronary dilation, whereas the dilating effect of acetylcholine was mainly microvascular. There was no correlation between the responses to the two drugs. L-NMMA did not affect the response to sodium nitroprusside, but it suppressed dilation in response to both substance P and acetylcholine, suggesting that the latter promote bioavailability of NO from the coronary vascular endothelium. Compared with patients without risks, those with hypercholesterolemia and hypertension had significantly reduced vasodilation with substance P:21% versus 12.6% (P=.004) increase in epicardial coronary diameter and 35% versus 19% (P<.05) decrease in vascular resistance. Similar differences were noted with acetylcholine but not with sodium nitroprusside or adenosine. Epicardial and microvascular dilations with substance P or acetylcholine after L-NMMA were similar in patients with and without risk factors, indicating that the reduced effect of endothelium-dependent vasodilators in those with hypertension and hypercholesterolemia is due to diminished NO activity. Conclusions (1) Substance P- and acetylcholine-induced coronary vasodilation, like that to acetylcholine, is at least partly due to stimulation of NO activity, indicating that the dysfunction of the coronary vascular endothelial cell layer is not restricted to muscarinic receptors. (2) Hypertension and hypercholesterolemia are associated with depression of both basal and pharmacologically stimulated bioavailability of NO.
引用
收藏
页码:104 / 110
页数:7
相关论文
共 52 条
  • [1] IMPAIRED MUSCARINIC ENDOTHELIUM-DEPENDENT RELAXATION AND CYCLIC GUANOSINE 5'-MONOPHOSPHATE FORMATION IN ATHEROSCLEROTIC HUMAN CORONARY-ARTERY AND RABBIT AORTA
    BOSSALLER, C
    HABIB, GB
    YAMAMOTO, H
    WILLIAMS, C
    WELLS, S
    HENRY, PD
    [J]. JOURNAL OF CLINICAL INVESTIGATION, 1987, 79 (01) : 170 - 174
  • [2] SUBSTANCE-P MECHANISMS IN THE REGULATION OF STRIATED-MUSCLE MICROCIRCULATION
    BROCK, JW
    JOSHUA, IG
    [J]. MICROVASCULAR RESEARCH, 1991, 41 (01) : 24 - 28
  • [3] THE ROLE OF NITRIC-OXIDE IN ENDOTHELIUM-DEPENDENT VASODILATION OF HYPERCHOLESTEROLEMIC PATIENTS
    CASINO, PR
    KILCOYNE, CM
    QUYYUMI, AA
    HOEG, JM
    PANZA, JA
    [J]. CIRCULATION, 1993, 88 (06) : 2541 - 2547
  • [4] IMPAIRED ENDOTHELIUM-DEPENDENT VASCULAR RELAXATION IN PATIENTS WITH HYPERCHOLESTEROLEMIA EXTENDS BEYOND THE MUSCARINIC RECEPTOR
    CASINO, PR
    KILCOYNE, CM
    CANNON, RO
    QUYYUMI, AA
    PANZA, JA
    [J]. AMERICAN JOURNAL OF CARDIOLOGY, 1995, 75 (01) : 40 - 44
  • [5] THE ROLE OF NITRIC-OXIDE IN MEDIATING ENDOTHELIUM DEPENDENT RELAXATIONS IN THE HUMAN EPICARDIAL CORONARY-ARTERY
    CHESTER, AH
    ONEIL, GS
    TADJKARIMI, S
    PALMER, RMJ
    MONCADA, S
    YACOUB, MH
    [J]. INTERNATIONAL JOURNAL OF CARDIOLOGY, 1990, 29 (03) : 305 - 309
  • [6] LOW BASAL AND STIMULATED RELEASE OF NITRIC-OXIDE IN ATHEROSCLEROTIC EPICARDIAL CORONARY-ARTERIES
    CHESTER, AH
    ONEIL, GS
    MONCADA, S
    TADJKARIMI, S
    YACOUB, MH
    [J]. LANCET, 1990, 336 (8720) : 897 - 900
  • [7] A COMPARISON OF BASAL AND AGONIST-STIMULATED RELEASE OF ENDOTHELIUM-DERIVED RELAXING FACTOR FROM DIFFERENT ARTERIES
    CHRISTIE, MI
    GRIFFITH, TM
    LEWIS, MJ
    [J]. BRITISH JOURNAL OF PHARMACOLOGY, 1989, 98 (02) : 397 - 406
  • [8] L-ARGININE IMPROVES ENDOTHELIUM-DEPENDENT VASODILATION IN HYPERCHOLESTEROLEMIC HUMANS
    CREAGER, MA
    GALLAGHER, SJ
    GIRERD, XJ
    COLEMAN, SM
    DZAU, VJ
    COOKE, JP
    [J]. JOURNAL OF CLINICAL INVESTIGATION, 1992, 90 (04) : 1248 - 1253
  • [9] RESPONSES OF ATHEROSCLEROTIC HUMAN CORONARY-ARTERIES INVIVO TO THE ENDOTHELIUM-DEPENDENT VASODILATOR SUBSTANCE-P
    CROSSMAN, DC
    LARKIN, SW
    DASHWOOD, MR
    DAVIES, GJ
    YACOUB, M
    MASERI, A
    [J]. CIRCULATION, 1991, 84 (05) : 2001 - 2010
  • [10] SUBSTANCE-P DILATES EPICARDIAL CORONARY-ARTERIES AND INCREASES CORONARY BLOOD-FLOW IN HUMANS
    CROSSMAN, DC
    LARKIN, SW
    FULLER, RW
    DAVIES, GJ
    MASERI, A
    [J]. CIRCULATION, 1989, 80 (03) : 475 - 484