Impaired endothelium-dependent vasodilation of large epicardial and resistance coronary arteries in patients with essential hypertension: Different responses to acetylcholine and substance P

Hypertensive patients have impaired endothelium-dependent coronary vasodilation evoked with acetylcholine. The aim of this study was to examine whether the impaired endothelium-dependent dilation of coronary arteries is related to a specific abnormality of the muscarinic receptor that mediates the effects of acetylcholine. Responses of the large epicardial and resistance coronary arteries were assessed in seven hypertensive patients (mean arterial pressure, 106±14 mm Hg) and seven control subjects (83±6 mm Hg, P<.01) during cardiac catheterization. To assess coronary endothelial function, we infused acetylcholine and substance P (endothelium-dependent agents that act on different receptors) and papaverine and nitrate (direct vascular smooth muscle dilators) into the left anterior descending coronary artery and determined coronary artery diameter by arteriography and coronary blood flow with an intracoronary Doppler catheter technique, In control subjects, 3 μg/min acetylcholine increased (P<.05) and 30 μg/min acetylcholine decreased (P<.05) arterial diameter, and in hypertensive patients, 1, 3, 10, and 30 μg/min acetylcholine decreased arterial diameter in a dose-dependent manner. Substance P at 3, 10, and 30 ng/min caused comparabit increases in diameter in both groups. Increases in coronary blood flow with both acetylcholine and substance P were significantly (P<.01) blunted in hypertensive patients compared with control subjects. No significant differences were noted between the groups in the responses of large epicardial coronary artery diameter and coronary blood flow to papaverine and nitrate. Vasodilation of the large coronary artery with acetylcholine was impaired, but the response to substance P was preserved in hypertensive patients, indicating that diminished vasodilation of the large epicardial coronary artery in hypertensive patients may be related to a specific abnormality in the endothelial muscarinic receptor. Blunted coronary blood flow responses to both acetylcholine and substance P in hypertensive patients suggest that endothelial dysfunction in the resistance coronary artery in this condition is related to a more generalized endothelial abnormality but is not confined to the muscarinic receptor.