The vasodilator action of nebivolol in forearm vasculature of subjects with essential hypertension

Citation
M. Dawes et al., The vasodilator action of nebivolol in forearm vasculature of subjects with essential hypertension, BR J CL PH, 48(3), 1999, pp. 460-463
Citations number
23
Categorie Soggetti
Pharmacology,"Pharmacology & Toxicology
Journal title
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
ISSN journal
03065251 → ACNP
Volume
48
Issue
3
Year of publication
1999
Pages
460 - 463
Database
ISI
SICI code
0306-5251(199909)48:3<460:TVAONI>2.0.ZU;2-W
Abstract
Aims Brachial artery administration of nebivolol increases forearm blood fl ow in normotensive subjects through activation of the L-arginine/NO pathway . The aim of the present study was to investigate the effect of brachial ar tery administration of nebivolol in subjects with essential hypertension. Methods We studied eight patients with uncomplicated essential hypertension and serum cholesterol less than 6.9 mmol l(-1). Antihypertensive medicatio n was discontinued 2 weeks before the study in previously treated patients. Following cannulation of the left brachial artery, saline was infused to e stablish baseline blood flow, followed by increasing doses of nebivolol (88 .5, 177 and 354 mu g min(-1), each dose for 6 min), followed by saline for 12 min, followed by a 30 min infusion of L-NMMA (2 mg min(-1)). During the final 18 min of the L-NMMA infusion, nebivolol was coinfused using the same doses as before. Forearm blood flow was measured in both arms using venous occlusion plethysmography. Results Blood flow in the noninfused arm did not change significantly throu ghout the study. In the infused arm blood flow increased significantly in a dose-related manner during the first series of nebivolol infusions from 2. 76 +/- 0.39 ml min(-1-1) 100 ml forearm(-1) during the baseline period to 4 .40+/-0.60 ml min(-1-1) 100 ml forearm(-1) (mean+/-s.e. mean, n = 8, P = 0. 0003 by ANOVA). L-NMMA antagonized the vasodilator effect of nebivolol: bas eline blood flow in the infused arm was 2.41 +/- 0.53 ml min(-1) 100 ml for earm(-1) and 2.94 +/- 0.42 ml min(-1) 100 ml forearm(-1) during coinfusion of the toy dose of nebivolol with L-NMMA (P = 0.0006 for an effect of L-NMM A on nebivolol response). There were no serious adverse events. Conclusions Nebivolol causes vasodilation in the forearm vascular bed in su bjects with essential hypertension. Since this response is antagonized by L -NMMA, the vasodilatation is probably caused by activation of the L-arg/NO pathway.