The vasodilator action of nebivolol in forearm vasculature of subjects with essential hypertension.
OBJECTIVE
Brachial artery administration of nebivolol increases forearm blood flow in normotensive subjects through activation of the L-arginine/NO pathway. The aim of the present study was to investigate the effect of brachial artery 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 medication was discontinued 2 weeks before the study in previously treated patients. Following cannulation of the left brachial artery, saline was infused to establish baseline blood flow, followed by increasing doses of nebivolol (88.5, 177 and 354 microg 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 throughout 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: baseline blood flow in the infused arm was 2.41+/-0.53 ml min-1 100 ml forearm-1 and 2.94+/-0.42 ml min-1 100 ml forearm-1 during coinfusion of the top dose of nebivolol with L-NMMA (P=0.0006 for an effect of L-NMMA on nebivolol response). There were no serious adverse events.


CONCLUSIONS
Nebivolol causes vasodilation in the forearm vascular bed in subjects with essential hypertension. Since this response is antagonized by L-NMMA, the vasodilatation is probably caused by activation of the L-arg/NO pathway.
Dawes
M
M
Department of Clinical Pharmacology, St Thomas's Hospital, Centre for Cardiovascular Biology and Medicine, King's College, London, UK.
Brett
S E
SE
Chowienczyk
P J
PJ
Mant
T G
TG
Ritter
J M
JM
D000293:Adolescent; D000328:Adult; D000368:Aged; D001578:Benzopyrans / Q000494:pharmacology* / Q000627:therapeutic use; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004983:Ethanolamines / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D005542:Forearm; D006801:Humans; D006973:Hypertension / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D000068577:Nebivolol; D012039:Regional Blood Flow / Q000187:drug effects; D014664:Vasodilation; D014665:Vasodilator Agents / Q000494:pharmacology* / Q000627:therapeutic use; D019323:omega-N-Methylarginine / Q000494:pharmacology
D001578:Benzopyrans; D004791:Enzyme Inhibitors; D004983:Ethanolamines; D014665:Vasodilator Agents; D000068577:Nebivolol; D019323:omega-N-Methylarginine