Impaired endothelium-mediated vasodilation is not the principal cause of vasoconstriction in heart failure

The extent to which abnormal endothelium-dependent vasodilator mechanisms c ontribute to abnormal resting vasoconstriction and blunted reflex vasodilat ion seen in heart failure is unknown. The purpose of this study was to test the hypothesis that the resting and reflex abnormalities in vascular tone that characterize heart failure are mediated by abnormal endothelium-mediat ed mechanisms. Thirteen advanced heart-failure patients (New York Heart Ass ociation III-IV) and 13 age-matched normal controls were studied. Saline, a cetylcholine (20 mu g/min), or L-arginine (10 mg/min) was infused into the brachial artery, and forearm blood flow was measured by venous plethysmogra phy at rest and during mental stress. At rest, acetylcholine decreased fore arm vascular resistance in normal subjects, but this response was blunted i n heart failure. During mental stress with intra-arterial acetylcholine or L-arginine, the decrease in forearm vascular resistance was not greater tha n during saline control in heart failure [saline control vs. acetylcholine (7 +/- 3 vs. 6 +/- 3, P = NS) or vs. L-arginine (9 +/- 2 units, P = NS)]. T he increase in forearm blood flow was not greater than during saline contro l in heart failure [saline control vs. acetylcholine (1.2 +/- 0.3 vs. 1.3 /- 0.3, P = NS), or vs. L-arginine (1.2 +/- 0.2 ml . min(-1) . 100 ml(-1), P = NS)]. Furthermore, during mental stress with nitroprusside, the decreas e in forearm vascular resistance was not greater than during saline control [saline control vs. nitroprusside (7 +/- 3 vs. 5 +/- 4 ml . min(-1) . 100 g(-1), P = NS)], and the increase in forearm blood flow was not greater tha n during saline control [saline control vs, nitroprusside (1.2 +/- 0.3 vs. 1.3 +/- 0.5 ml . min(-1) . 100 g(-1), P = NS)]. Because the endothelial-ind ependent agent nitroprusside was unable to restore resting and reflex vasod ilation to normal in heart failure, we conclude that impaired endothelium-m ediated vasodilation with acetylholine-nitric oxide cannot be the principal cause of the attenuated resting- or reflex-mediated vasodilation in heart failure.