Author + information
- Received October 13, 1993
- Revision received December 23, 1993
- Accepted January 5, 1994
- Published online June 1, 1994.
- Julio A. Panza, MD∗,
- Philip R. Casino, MD,
- Crescence M. Kilcoyne, RN and
- Arshed A. Quyyumi, MD, FACC
- ↵∗Address for correspondence:Dr. Julio A. Panza, National Institutes of Health, Building 10, Room 7B-15, Bethesda, Maryland 20892.
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.
- Received October 13, 1993.
- Revision received December 23, 1993.
- Accepted January 5, 1994.