Impaired endothelium-dependent vasodilation in patients with essential hypertension: Evidence that the abnormality is not at the muscarinic receptor level

Abstract

Objectives. The purpose of this study was to determine whether the impaired endothelium-dependent vasodilation of hypertensive patients is related to a specific defect of the muscarinic receptor or to a broader abnormality of the vascular endothelium.Background. Patients with essential hypertension have abnormal endothelium-dependent vasodilator response to acetylcholine. However, whether this results from an isolated dysfunction of the endothelial cell muscarinic receptor b unknown. Methods. The responses of the forearm vasculature to acetyl-choline and substance P (endothelium-dependent agents acting on different receptors) and to sodium nitroprusside (a direct dilator of vascular smooth muscle) were studied in eight hypertensive patients (six men, two women; mean age [±SD] 50 ± 12 years) and eight normal control subjects (four men, four women; mean age 49 ± 9 years). To determine the nitric oxide contribution to substance P-induced vasodilation, the vascular responses to substance P were also measured after inhibition of nitric oxide synthesis with NG-monomethyl-l-arginine. Drugs were infused into the brachial artery, and forearm blood flow was measured by strain gauge plethysmography.Results. The response to acetylcholine was significantly blunted in hypertensive patients (highest blood flow [mean ± SD] 8.4 ± 4 vs. 13.8 ± 4 ml/min per 100 ml in control subjects, p < 0.03). Similarly, the vasodilator effect of substance P was significantly reduced in hypertensive patients (highest blood flow [mean ± SD] 8.8 ± 4 vs. 13.9 ± 4 ml/min per 100 ml in control subjects, p < 0.03). A significant correlation was found between the maximal blood flow with acetylcholine and that with substance P (r = 0.68, p < 0.004). The vasodilator response to sodium nitroprousside was similar in patients and control subjects. The nitric oxide contribution to substance P-induced vasodilation was reduced in hypertensive patients, such that the responses to substance P measured during infusion of NG-monomethyl-l-arginine were not significantly different between the two groups.Conclusions. These findings indicate that the endothelial abnormality of patients wtth essential hypertension is not restricted to the muscarinic cell receptor.