Nebivolol induces parallel improvement of left ventricular filling pressure and coronary flow reserve in uncomplicated arterial hypertension.
OBJECTIVE
Our aim was to analyze the effects of 3-month antihypertensive therapy by nebivolol, a beta-blocking agent with nitric oxide-mediated vasodilatory properties, on coronary flow reserve (CFR) and left ventricular filling pressure (LVFP) in uncomplicated arterial hypertension.


METHODS
Twenty newly diagnosed, never treated, uncomplicated hypertensive patients (14 male and six female patients, mean age = 49 years), I-II WHO grade, underwent single-blind nebivolol treatment. At baseline and at 3-month follow-up, patients underwent Doppler echocardiography including pulsed Tissue Doppler of septal mitral annulus: the ratio between transmitral E velocity and myocardial early diastolic velocity (E/Em ratio) was calculated as an index of LVFP degree. Transthoracic Doppler-derived CFR (high-dose dipyridamole coronary diastolic peak flow velocity to resting coronary peak flow velocity ratio) of distal left anterior descending artery was also determined.


RESULTS
After 3-month nebivolol therapy, rate-pressure product decreased (P < 0.0001). No significant change of left ventricular mass index, relative wall thickness and midwall shortening was detected. Left ventricular end-diastolic diameter and stroke volume were both marginally increased. Nebivolol increased Em (P < 0.0001), reduced E/Em ratio (from 9.0 +/- 1.6 to 8.2 +/- 1.1, P < 0.0001) and enhanced CFR (from 2.07 +/- 0.2 to 2.20 +/- 0.2, P = 0.003), because of increased hyperemic coronary flow velocity (P < 0.001). CFR increase remained significant (P < 0.001) after normalizing resting and dipyridamole coronary velocities for the respective rate-pressure product. The increase of normalized CFR induced by nebivolol was related with E/Em ratio decrease (r = -0.65, P < 0.002).


CONCLUSIONS
Nebivolol improves LVFP as well as CFR in uncomplicated hypertension. The association between changes of CFR and those of LVFP indicates a possible common denominator between improvement of coronary microvascular function and myocardial stimulation of nitric oxide release induced by the drug.
Galderisi
Maurizio
M
Echocardiography Laboratory, Department of Clinical and Experimental Medicine, Federico II University Hospital of Naples, Block 1, Via S. Pansini 5, 80131 Naples, Italy. mgalderi@unina.it
D'Errico
Arcangelo
A
Sidiropulos
Milena
M
Innelli
Pasquale
P
de Divitiis
Oreste
O
de Simone
Giovanni
G
D000959:Antihypertensive Agents / Q000008:administration & dosage*; D001578:Benzopyrans / Q000008:administration & dosage*; D003326:Coronary Circulation / Q000187:drug effects; D015150:Echocardiography, Doppler; D004983:Ethanolamines / Q000008:administration & dosage*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000188:drug therapy*; D017379:Hypertrophy, Left Ventricular / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000209:etiology; D008297:Male; D008875:Middle Aged; D000068577:Nebivolol; D009569:Nitric Oxide / Q000378:metabolism; D016037:Single-Blind Method; D016896:Treatment Outcome; D016277:Ventricular Function, Left / Q000187:drug effects*; D017725:Ventricular Pressure / Q000187:drug effects
D000959:Antihypertensive Agents; D001578:Benzopyrans; D004983:Ethanolamines; D000068577:Nebivolol; D009569:Nitric Oxide