Blocking Action of Nicardipine on alpha1-Adrenoceptors in Circulatory System of Rabbit

ABSTRACT

To investigate relationship between alpha1-acrenoceptors and nicardipine, an 1,4-dihydropyridine calcium antagonist, effects of nicardipine, on phenylephrinne(PE)-induced vasoconstriction in isolated arterial rings and pressor response of rabbits were observed. In normal physiological salt solution(NPSS), 35mM KCI produced persistent contractions of thoracic aorta and carotid artery and the contractions were dose-dependently inhoboted by cumulative admini-stration of nicardipine in the range of doses from 10(-10)M to 10(-4)M, IC50s of nicardipine in the thoracic aorta and carotid artery were 3.3x10(-7)M and 4.6x10(-7)M, respectively and there was no difference between both values. Constant contractions induced by 10(-5)M PE in both rings were inhibited by the same doses of nicardipine in a dose-dependent fashion. The IC50s were 2.8x10(-4)M in thoracic aorta and 2.9x10(-5)M in carotid artery respectively, and the former was about 10 times greater than the latter. In Ca2+ free PSS, KCI did not produce any contractionn. Though constant and reproducible in NPSS, PE-induced contraction was transient and not reproducible in Ca2+ free PSS. The contraction in both rings were weakened to about 70% of those in NPSS. Pretreatment with nicardipine in the range of doses from 10-8M to 10-5M hardly affected the PE-induced contraction and the largest dose 10(-4)M slightly inhibited the contraction. Intravenous injection of nicardipine 10 to 1000microg/kg decreased blood pressure and heart rate of rabbits in a dose-dependent manner. The % decrease of heart rate was much smaller in comparison with the %decrease of blood presseure. Pressor effect of 30microg/kg PE was dose-dependently inhibited after treatment with nicardipine 10 to 1000microg/kg and ID50 was 314microg/kg(6.1x10(-7)mole/kg). Above results suggest that nicardipine blocks extracellulr Ca2+ influx by membrane depolarization and in a part by alpha1-adrenceptors, then relaxes arterial smooth muscles in rabbits.