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 vas odilation evoked with acetylcholine. The aim of this study was to exam ine whether the impaired endothelium-dependent dilation of coronary ar teries is related to a specific abnormality of the muscarinic receptor that mediates the effects of acetylcholine. Responses of the large ep icardial and resistance coronary arteries were assessed in seven hyper tensive patients (mean arterial pressure, 106+/-14 mm Hg) and seven co ntrol subjects (83+/-6 mm Hg, P<.01) during cardiac catheterization. T o assess coronary endothelial function, we infused acetylcholine and s ubstance P (endothelium-dependent agents that act on different recepto rs) and papaverine and nitrate (direct vascular smooth muscle dilators ) into the left anterior descending coronary artery and determined cor onary artery diameter by arteriography and coronary blood flow with an intracoronary Doppler catheter technique. In control subjects, 3 mu g /min acetylcholine increased (P<.05) and 30 mu g/min acetylcholine dec reased (P<.05) arterial diameter, and in hypertensive patients, 1, 3, 10, and 30 mu g//min acetylcholine decreased arterial diameter in a do se-dependent manner. Substance P at 3, 10, and 30 ng/min caused compar able increases in diameter in both groups. Increases in coronary blood how 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 w ith acetylcholine was impaired, but the response to substance P was pr eserved in hypertensive patients, indicating that diminished vasodilat ion of the large epicardial coronary artery in hypertensive patients m ay 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 dysf unction in the resistance coronary artery in this condition is related to a more generalized endothelial abnormality but is not confirmed to the muscarinic receptor.