Effects of the vasodilating beta-blocker nebivolol on smoking-induced endothelial dysfunction in young healthy volunteers.
OBJECTIVE
To assess the effect of nebivolol, a highly selective third generation beta1-adrenoceptor antagonist with an endothelium-dependent vasodilatory action, on smoking-induced endothelial dysfunction.


METHODS
This open-label study examined the effect of 14 daily doses of 5 mg nebivolol on forearm blood flow in 21 healthy, young, male, light smokers (< or =5 cigarettes/day), measured by plethysmography on Days 1, 7, and 14. The primary endpoint was the difference in forearm blood flow after smoking one standard cigarette from baseline (Day 1) until treatment end on Day 14. Secondary outcomes included the difference in forearm blood flow between Day 1 and Day 7 compared with Day 14 before and after smoking, the effect of nebivolol on blood coagulation parameters, high-sensitive-C-reactive protein (hs-CRP), and the safety and tolerability of nebivolol.


RESULTS
Nebivolol for 14 days did not significantly affect forearm blood flow after smoking. On Day 7 of nebivolol treatment, forearm blood flow after smoking was significantly greater than blood flow before smoking (increase of 0.44 mL/min; p = 0.00656). Serum level ofhs-CRP showed a marked decrease from Day 1 to Day 14. No changes in coagulation parameters were observed over the course of nebivolol treatment. Nebivolol was well tolerated throughout the study.


CONCLUSIONS
The increase in forearm blood flow and the marked decrease in hs-CRP over 14 days of treatment suggest that nebivolol has a positive effect on endothelial function in light smokers, but larger studies are required to confirm these observations.
Schmidt
André C
AC
Charité-Universitätsmedizin Berlin, Institute for Clinical Pharmacology and Toxikology, Berlin, Germany. andre.schmidt@charite.de
Flick
Burkhard
B
Jahn
Elke
E
Bramlage
Peter
P
D000293:Adolescent; D000319:Adrenergic beta-Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D000328:Adult; D001578:Benzopyrans / Q000009:adverse effects / Q000627:therapeutic use*; D001777:Blood Coagulation / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D002097:C-Reactive Protein / Q000378:metabolism; D004562:Electrocardiography; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology; D004983:Ethanolamines / Q000009:adverse effects / Q000627:therapeutic use*; D005542:Forearm / Q000098:blood supply*; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D000068577:Nebivolol; D010865:Pilot Projects; D010991:Plethysmography; D012039:Regional Blood Flow / Q000187:drug effects; D012907:Smoking / Q000009:adverse effects* / Q000097:blood / Q000503:physiopathology; D013997:Time Factors; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000009:adverse effects / Q000627:therapeutic use*; D055815:Young Adult
D000319:Adrenergic beta-Antagonists; D001578:Benzopyrans; D004983:Ethanolamines; D018836:Inflammation Mediators; D014665:Vasodilator Agents; D000068577:Nebivolol; D002097:C-Reactive Protein