In anesthetized dogs, an
intravenous injection of
nipradilol produced a long lasting fall in mean arterial blood pressure which was accompanied by transient decreases in peripheral vascular resistance and sustained decreases in heart rate, cardiac output and left ventricular (LV) dP/dt. LV end-diastolic pressure (LVEDP) was not changed while LV diameters and central venous pressure were slightly increased. Under
propranolol pretreatment conditions,
nipradilol no longer affected the heart rate, but the
drug still induced a transient reduction in peripheral vascular resistance, and sustained decreases in arterial blood pressure and cardiac output. Furthermore, indicators of LV preload (LVEDP, LV end-diastolic diameter and central venous pressure) were significantly reduced, suggesting a direct dilating action of
nipradilol on capacitance vessels. In intact conscious dogs,
nipradilol caused a sustained reduction in LVEDP, while
propranolol increased LVEDP. After administration of
nipradilol, coronary blood flow in anesthetized dogs decreased in association with diminished myocardial oxygen consumption, and large coronary vessel resistance also decreased.
Nipradilol competitively antagonized the
isoproterenol-induced positive chronotropic response (DR10: 0.04 mg/Kg, i.v.) and the
phenylephrine-induced vasopressor response (DR10: 3.95 mg/Kg, i.v.). In conclusion,
nipradilol, in contrast to
propranolol, possesses the properties to decrease arterial blood pressure, LV preload and large coronary vessel resistance through its dilating action on arterial and venous vessels. It is proposed that
nipradilol may be beneficial for the treatment of
hypertension and
coronary heart disease.