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
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.