Effects of
prizidilol and
nipradilol (K-351),
beta-adrenoceptor antagonists with
vasodilator action, on blood pressure and heart rate were studied in normotensive conscious rabbits after i.v. administration. In addition, we investigated relationships between plasma
drug concentrations and beta-
adrenoceptor blocking activity as estimated by the inhibition of
isoproterenol-induced
tachycardia and
vasodilator activity as assessed by the inhibition of pressor response to
angiotensin II (ANG II).
Prizidilol (4 mg/kg) produced a significant and sustained fall in blood pressure and a slight increase in heart rate, while
hydralazine (2 mg/kg) caused the same degree of
hypotension and a marked
tachycardia.
Nipradilol (1 mg/kg) caused a significant reduction of resting heart rate, but had no significant effect on blood pressure.
Propranolol (1 mg/kg) did not affect resting blood pressure and heart rate. Hypertensive response to ANG II was significantly attenuated only by
hydralazine.
Isoproterenol-induced
tachycardia was significantly suppressed by
prizidilol,
nipradilol and
propranolol. Good correlations were observed between beta-
adrenoceptor blocking activity and plasma
drug concentrations. These data suggest that
prizidilol has an advantage over
hydralazine to induce less
tachycardia, but still may cause a certain degree of increase in heart rate.
Nipradilol has a more potent beta-
adrenoceptor blocking action than
propranolol, while its
vasodilator action is not obvious, at least in rabbits. Plasma concentrations of
prizidilol and
nipradilol are good indicators for beta-
adrenoceptor blocking activity, but not for
vasodilator activity.