Cardiovascular effects of nipradilol, a beta-adrenoceptor blocker with vasodilating properties.
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.
Fujii
M
M
Shirasawa
Y
Y
Kondo
S
S
Sawanobori
K
K
Nakamura
M
M
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects; D004285:Dogs; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D007275:Injections, Intravenous; D009206:Myocardium / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D011412:Propanolamines / Q000494:pharmacology*; D014655:Vascular Resistance / Q000187:drug effects; D014665:Vasodilator Agents
D000319:Adrenergic beta-Antagonists; D011412:Propanolamines; D014665:Vasodilator Agents; C036089:nipradilol