(Circulation. 1997;95:104-110.)
© 1997 American Heart Association, Inc.
Articles |
Coronary Vascular Nitric Oxide Activity in Hypertension and Hypercholesterolemia
Comparison of Acetylcholine and Substance P
the National Institutes of Health, Cardiology Branch, NHLBI, Bethesda, Md.
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 NG-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.
Key Words: endothelium • hypercholesterolemia • acetylcholine • endothelium-derived factors • hypertension
This article has been cited by other articles:
 |
|
 |
|
  M. Seddon, N. Melikian, R. Dworakowski, H. Shabeeh, B. Jiang, J. Byrne, B. Casadei, P. Chowienczyk, and A. M. Shah Effects of Neuronal Nitric Oxide Synthase on Human Coronary Artery Diameter and Blood Flow In Vivo Circulation, May 26, 2009; 119(20): 2656 - 2662. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Barac, U. Campia, and J. A. Panza Methods for Evaluating Endothelial Function in Humans Hypertension, April 1, 2007; 49(4): 748 - 760. [Full Text] [PDF]
|
|
|
|
 |
|
 S. Al-Benna, C. A. Hamilton, J. D. McClure, P. N. Rogers, G. A. Berg, I. Ford, C. Delles, and A. F. Dominiczak Low-Density Lipoprotein Cholesterol Determines Oxidative Stress and Endothelial Dysfunction in Saphenous Veins From Patients With Coronary Artery Disease Arterioscler. Thromb. Vasc. Biol., January 1, 2006; 26(1): 218 - 223. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Tomai, F. Ribichini, A. S. Ghini, V. Ferrero, G. Ando, C. Vassanelli, F. Romeo, F. Crea, and L. Chiariello Elevated C-reactive protein levels and coronary microvascular dysfunction in patients with coronary artery disease Eur. Heart J., October 2, 2005; 26(20): 2099 - 2105. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Neishi, S. Mochizuki, T. Miyasaka, T. Kawamoto, T. Kume, R. Sukmawan, M. Tsukiji, Y. Ogasawara, F. Kajiya, T. Akasaka, et al. Evaluation of bioavailability of nitric oxide in coronary circulation by direct measurement of plasma nitric oxide concentration PNAS, August 9, 2005; 102(32): 11456 - 11461. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Takahashi, T. Komaru, S. Takeda, K. Sato, H. Kanatsuka, and K. Shirato Nitric oxide inhibition unmasks ischemic myocardium-derived vasoconstrictor signals activating endothelin type A receptor of coronary microvessels Am J Physiol Heart Circ Physiol, July 1, 2005; 289(1): H85 - H91. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. R. Hyduke and J. C. Liao Analysis of nitric oxide donor effectiveness in resistance vessels Am J Physiol Heart Circ Physiol, May 1, 2005; 288(5): H2390 - H2399. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. A DeSouza, C. M Clevenger, J. J Greiner, D. T Smith, G. L Hoetzer, L. F Shapiro, and B. L Stauffer Evidence for agonist-specific endothelial vasodilator dysfunction with ageing in healthy humans J. Physiol., July 1, 2002; 542(1): 255 - 262. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Giannattasio, A. Piperno, M. Failla, A. Vergani, and G. Mancia Effects of Hematocrit Changes on Flow-Mediated and Metabolic Vasodilation in Humans Hypertension, July 1, 2002; 40(1): 74 - 77. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Giannattasio, F. Achilli, A. Grappiolo, M. Failla, E. Meles, G. Gentile, I. Calchera, A. Capra, J. Baglivo, A. Vincenzi, et al. Radial Artery Flow-Mediated Dilatation in Heart Failure Patients: Effects of Pharmacological and Nonpharmacological Treatment Hypertension, December 1, 2001; 38(6): 1451 - 1455. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M.P. Pellegrini, D. E Newby, S. Maxwell, and D. J Webb Short-term effects of transdermal nicotine on acute tissue plasminogen activator release in vivo in man Cardiovasc Res, November 1, 2001; 52(2): 321 - 327. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. J. Grieve, P. A. MacCarthy, N. P. Gall, A. C. Cave, and A. M. Shah Divergent Biological Actions of Coronary Endothelial Nitric Oxide During Progression of Cardiac Hypertrophy Hypertension, August 1, 2001; 38(2): 267 - 273. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. P. Andrews, M. Husain, N. Dakak, and A. A. Quyyumi Platelet inhibitory effect of nitric oxide in the human coronary circulation: impact of endothelial dysfunction J. Am. Coll. Cardiol., February 1, 2001; 37(2): 510 - 516. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. M. Webb, M. A. Ghatei, J. G. McNeill, DCRR, and P. Collins 17{beta}-Estradiol Decreases Endothelin-1 Levels in the Coronary Circulation of Postmenopausal Women With Coronary Artery Disease Circulation, October 3, 2000; 102(14): 1617 - 1622. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A. Vita, A. C. Yeung, M. Winniford, J. M. Hodgson, C. B. Treasure, J. L. Klein, S. Werns, M. Kern, D. Plotkin, W. J. Shih, et al. Effect of Cholesterol-Lowering Therapy on Coronary Endothelial Vasomotor Function in Patients With Coronary Artery Disease Circulation, August 22, 2000; 102(8): 846 - 851. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. E NEWBY Intracoronary infusions and the assessment of coronary blood flow in clinical studies Heart, August 1, 2000; 84(2): 118 - 120. [Full Text] [PDF]
|
|
|
|
|
|
T. W. Hein, J. C. Liao, and L. Kuo oxLDL specifically impairs endothelium-dependent, NO-mediated dilation of coronary arterioles Am J Physiol Heart Circ Physiol, January 1, 2000; 278(1): H175 - H183. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Glorioso, C. Troffa, F. Filigheddu, F. Dettori, A. Soro, P. P. Parpaglia, S. Collatina, and M. Pahor Effect of the HMG-CoA Reductase Inhibitors on Blood Pressure in Patients With Essential Hypertension and Primary Hypercholesterolemia Hypertension, December 1, 1999; 34(6): 1281 - 1286. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D Tousoulis, C Tentolouris, T Crake, C Stefanadis, P Toutouzas, and G Davies Evidence of partially preserved endothelial dilator function in diseased coronary arteries Heart, October 1, 1999; 82(4): 471 - 476. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Heymes, M. Vanderheyden, J. G. F. Bronzwaer, A. M. Shah, and W. J. Paulus Endomyocardial Nitric Oxide Synthase and Left Ventricular Preload Reserve in Dilated Cardiomyopathy Circulation, June 15, 1999; 99(23): 3009 - 3016. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. J. Mhanna, I. A. Dreshaj, M. A. Haxhiu, and R. J. Martin Mechanism for substance P-induced relaxation of precontracted airway smooth muscle during development Am J Physiol Lung Cell Mol Physiol, January 1, 1999; 276(1): L51 - L56. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Tousoulis, G. Davies, T. Crake, A. Lerman, D. Hasdai, and D. Holmes Acetylcholine and Endothelial Function • Response Circulation, October 13, 1998; 98 (15): 1587 - 1590. [Full Text] [PDF]
|
|
|
|
|
|
A. A. Quyyumi Does acute improvement of endothelial dysfunction in coronary artery disease improve myocardial ischemia?: A double-blind comparison of parenteral D- and L-Arginine J. Am. Coll. Cardiol., October 1, 1998; 32(4): 904 - 911. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Metais, J. Li, J. Li, M. Simons, and F. W. Sellke Effects of coronary artery disease on expression and microvascular response to VEGF Am J Physiol Heart Circ Physiol, October 1, 1998; 275(4): H1411 - H1418. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. G. Diodati, N. Dakak, D. M. Gilligan, and A. A. Quyyumi Effect of Atherosclerosis on Endothelium-Dependent Inhibition of Platelet Activation in Humans Circulation, July 7, 1998; 98(1): 17 - 24. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. C. McGill Jr, C. A. McMahan, R. E. Tracy, M. C. Oalmann, J. F. Cornhill, E. E. Herderick, and J. P. Strong Relation of a Postmortem Renal Index of Hypertension to Atherosclerosis and Coronary Artery Size in Young Men and Women Arterioscler. Thromb. Vasc. Biol., July 1, 1998; 18(7): 1108 - 1118. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Dakak, S. Husain, D. Mulcahy, N. P. Andrews, J. A. Panza, M. Waclawiw, W. Schenke, and A. A. Quyyumi Contribution of Nitric Oxide to Reactive Hyperemia : Impact of Endothelial Dysfunction Hypertension, July 1, 1998; 32(1): 9 - 15. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Lerman, J. C. Burnett Jr, S. T. Higano, L. J. McKinley, and D. R. Holmes Jr Long-term L-Arginine Supplementation Improves Small-Vessel Coronary Endothelial Function in Humans Circulation, June 2, 1998; 97(21): 2123 - 2128. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U. Bayraktutan, Z.-K. Yang, and A. M Shah Selective dysregulation of nitric oxide synthase type 3 in cardiac myocytes but not coronary microvascular endothelial cells of spontaneously hypertensive rat Cardiovasc Res, June 1, 1998; 38(3): 719 - 726. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. E Newby, R. A Wright, P. Dawson, C. A Ludlam, N. A Boon, K. A.A Fox, and D. J Webb The L-arginine/nitric oxide pathway contributes to the acute release of tissue plasminogen activator in vivo in man Cardiovasc Res, May 1, 1998; 38(2): 485 - 492. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Husain, N. P. Andrews, D. Mulcahy, J. A. Panza, and A. A. Quyyumi Aspirin Improves Endothelial Dysfunction in Atherosclerosis Circulation, March 3, 1998; 97(8): 716 - 720. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U. C. Kopp, M. Z. Cicha, D. M. Farley, L. A. Smith, and B. S. Dixon Renal Substance P–Containing Neurons and Substance P Receptors Impaired in Hypertension Hypertension, March 1, 1998; 31(3): 815 - 822. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Ichiki, M. Usui, M. Kato, Y. Funakoshi, K. Ito, K. Egashira, and A. Takeshita Downregulation of Angiotensin II Type 1 Receptor Gene Transcription by Nitric Oxide Hypertension, January 1, 1998; 31(1): 342 - 346. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Kato, N. Shiode, T. Yamagata, H. Matsuura, and G. Kajiyama Bradykinin induced dilatation of human epicardial and resistance coronary arteries in vivo: effect of inhibition of nitric oxide synthesis Heart, November 1, 1997; 78(5): 493 - 498. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. H. McDermott, J. P.J. Halcox, W. H. Schenke, M. A. Waclawiw, M. N. Merrell, N. Epstein, A. A. Quyyumi, and P. M. Murphy Association Between Polymorphism in the Chemokine Receptor CX3CR1 and Coronary Vascular Endothelial Dysfunction and Atherosclerosis Circ. Res., August 31, 2001; 89(5): 401 - 407. [Abstract] [Full Text] [PDF]
|
|