Epicardial coronary artery responses to acetylcholine are impaired in hypertensive patients.
Hypertension is a risk factor for coronary atherosclerosis possibly via an adverse effect on the vascular endothelium. Endothelium-mediated relaxation is impaired in animal models of hypertension. However, the effects of hypertension on human coronary artery endothelial cell function are unknown. To test whether endothelium-mediated relaxation is impaired in the coronary arteries of patients with hypertension, we studied 14 patients with essential hypertension requiring therapy and 15 nonhypertensive control patients undergoing cardiac catheterization. All had angiographically normal, smooth-appearing coronary arteries. Patients were matched for age and other coronary atherosclerosis risk factors. To assess endothelial cell function, the endothelium-dependent vasodilator acetylcholine (ACh, 0.01, 0.1, and 1.0 microM) and the endothelium-independent vasodilator nitroglycerin (40 micrograms) were selectively infused into the left anterior descending or circumflex coronary artery. Diameter change (expressed as percent) was assessed using quantitative angiography. There was a marked vasoconstrictor response to serial doses of ACh in hypertensive patients (-7%, -21%, and -27%) compared with control patients (-4%, -5%, and -7%) (p less than 0.02). The vasodilator response to nitroglycerin was preserved in hypertensive patients (+29%) and control patients (+25%) (p = NS), suggesting that endothelial cell dysfunction accounted for the differences in response to ACh. Thus, patients with hypertension have an accentuated coronary vasoconstrictor response to ACh, suggesting that endothelium-mediated regulation of coronary vascular tone is impaired by essential hypertension. This may reflect more generalized coronary endothelial changes contributing to the pathogenesis of atherosclerosis as well as hypertension.
Treasure
C B
CB
Division of Cardiology, Emory University School of Medicine, Atlanta, GA 30303.
Manoukian
S V
SV
Klein
J L
JL
Vita
J A
JA
Nabel
E G
EG
Renwick
G H
GH
Selwyn
A P
AP
Alexander
R W
RW
Ganz
P
P
D000109:Acetylcholine / Q000008:administration & dosage / Q000494:pharmacology*; D000328:Adult; D017023:Coronary Angiography; D003327:Coronary Disease / Q000209:etiology; D003331:Coronary Vessels / Q000187:drug effects* / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology; D005260:Female; D006801:Humans; D006973:Hypertension / Q000503:physiopathology*; D007263:Infusions, Parenteral; D008297:Male; D008875:Middle Aged; D005996:Nitroglycerin / Q000008:administration & dosage / Q000494:pharmacology
D005996:Nitroglycerin; D000109:Acetylcholine