IMPAIRED ENDOTHELIUM-DEPENDENT VASODILATION IN PATIENTS WITH ESSENTIAL-HYPERTENSION - EVIDENCE THAT THE ABNORMALITY IS NOT AT THE MUSCARINIC RECEPTOR LEVEL

Objectives. The purpose of this study was to determine whether the imp aired endothelium dependent vasodilation of hypertensive patients is r elated to a specific defect of the muscarinic receptor or to a broader abnormality of the vascular endothelium. Background. Patients with es sential hypertension have abnormal endothelium dependent vasodilator r esponse to acetylcholine. However, whether this results from an isolat ed dysfunction of the endothelial cell muscarinic receptor is unknown. Methods. The responses of the forearm vasculature to acetyl choline a nd substance P (endothelium dependent agents acting on different recep tors) and to sodium nitroprusside (a direct dilator of vascular smooth muscle) were studied in eight hypertensive patients (six men, two wom en; mean age [+/-SD] 50 +/- 12 years) and eight normal control subject s (four men, four women; mean age 49 +/- 9 years). To determine the ni tric oxide contribution to substance P-induced vasodilation, the vascu lar responses to substance P were also measured after inhibition of ni tric oxide synthesis with N-G-monomethyl-L-arginine. Drugs were infuse d into the brachial artery, and forearm blood flow was measured by str ain gauge plethysmography. Results. The response to acetylcholine was significantly blunted in hypertensive patients (highest blood now [mea n +/- SD] 8.4 +/- 4 vs. 13.8 +/- 4 ml/min per 100 mi in control subjec ts, p < 0.03). Similarly, the vasodilator effect of substance P was si gnificantly reduced in hypertensive patients (highest blood flow [mean +/- SD] 8.8 +/- 4 vs. 13.9 +/- 4 ml/min per 100 mi in control subject s, p < 0.03). A significant correlation was found between the maximal blood Bow with acetylcholine and that with substance P (r = 0.68, p < 0.004). The vasodilator response to sodium nitroprusside was similar i n patients and control subjects, The nitric oxide contribution to subs tance P-induced vasodilation was reduced in hypertensive patients, suc h that the responses to substance P measured during infusion of N-G-mo nomethyl L arginine were not significantly different between the two g roups. Conclusions. These findings indicate that the endothelial abnor mality of patients with essential hypertension is not restricted to th e muscarinic cell receptor.