Nebivolol induces parallel improvement of left ventricular filling pressure and coronary flow reserve in uncomplicated arterial hypertension

Purpose 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/E-m 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 enddiastolic diameter and stroke volume were both marginally increased. Nebivolol increased E-m (P<0.0001), reduced E/E-m 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/E-m ratio decrease (r=-0.65, P<0.002). Conclusion 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. J Hypertens 27: 2108-2115 (C) 2009 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.