It has been shown that endothelium-dependent vasorelaxation in response to muscarinic stimulation is attenuated in patients as well as animals with heart failure. This study aimed to determine if endothelium-dependent forearm vasodilation evoked with substance P (SP) as well as acetylcholine (ACh) was impaired in patients with heart failure. Forearm blood flow was measured using a strain-gauge plethysmograph and forearm vascular responses to intra- arterial infusions of ACh, SP, or sodium nitroprusside (SNP) at graded doses were examined. The drugs caused the dose-dependent increases in forearm blood flow (FBF) and the decreases in forearm vascular resistance (FVR) in patients with heart failure as well as normal subjects. However, the percent decreases in FVR by ACh were less in patients with heart failure than in normal subjects (p < 0.01). In contrast, the percent decreases in FVR by SP or SNP did not differ between the two groups. These results suggest that endothelium-dependent vasodilation of forearm resistance vessels via muscarinic receptors is specifically impaired, whereas via SP receptors is preserved in patients with heart failure.
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