IMPAIRED ENDOTHELIUM-DEPENDENT VASODILATION IN PATIENTS WITH ESSENTIAL-HYPERTENSION - EVIDENCE THAT THE ABNORMALITY IS NOT AT THE MUSCARINIC RECEPTOR LEVEL
Ja. Panza et al., IMPAIRED ENDOTHELIUM-DEPENDENT VASODILATION IN PATIENTS WITH ESSENTIAL-HYPERTENSION - EVIDENCE THAT THE ABNORMALITY IS NOT AT THE MUSCARINIC RECEPTOR LEVEL, Journal of the American College of Cardiology, 23(7), 1994, pp. 1610-1616
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.