Mechanisms of blunted muscle vasodilation during peripheral chemoreceptor stimulation in heart failure patients

Abstract

Purpose: We recently described that systemic hypoxia provokes vasoconstriction in HF patients, Which might due to augmented sympathetic nerve activity to muscle (MSNA), in this study, we tested the hypothesis that either the exaggerated MSNA and/or blunted endothelial dysfunction mediate the blunted vasodilation during hypoxia in HF patients. Methods: Twenty seven HF patients and 23 age-matched healthy controls were studied. MSNA was assessed by microneurography and forearm blood flow (FBF) by venous occlusion plethysmography. Peripheral chemoreflex control was evaluated through the inhaling of a hypoxic gas mixture (10% O2 and 90% N2). Results: MSNA (P=0.001) were greater and basal FBF levels (P=0.003) were lower in HF patients versus controls. During hypoxia, MSNA responses were greater in HF patients (P=0.02), and forearm vasodilatation was blunted in HF compared to controls (P=0.002). In the presence of phentolamine, hypoxia significantly increased FBF responses in both groups, but the increase was lower in HF patients versus controls (P=0.003). Phentolamine + L-NMMA infusion during hypoxia did not change FBF responses in HF, but markedly blunted the vasodilatation in controls (P=0.96). FBF responses to hypoxia in the presence of vitamin C, an antioxidant that promotes NO availability, were unch anged when compared with saline infusion, and remained lower in HF patients versus controls. Conclusions: Muscle vasoconstriction in response to hypoxia in HF patients is due to exaggerated reflex sympathetic nerve activation and blunted endothelial function (NO activity). We were unable to identify a role for oxidative stress in these studies.