Actions of Calcium Agonists and Antagonists on Femoral Arteries of Spontaneously Hypertensive Rats

Abstract

The Ca2+ agonist actions of Bay k 8644, a Ca2+ agonist, on femoral arteries from 6-week-old spontaneously hypertensive rats (SHR) were investigated and the data compared with findings in normotensive Wistar-Kyoto rats (WKY). The addition of Bay k 8644 produced a dose-dependent contraction in the SHR femoral artery with a pD2 value of 8.55. The maximum contraction induced by this Ca2 + agonist (1 x 10–7 M) was comparable with the maximum developed by either K+ depolarization or alpha adrenoceptor stimulation. The SHR femoral artery was more sensitive to the contractile response to Bay k 8644 than to that to alpha adrenoceptor stimulation. Bay k 8644 was much less effective in eliciting the contractile effects on the WKY femoral artery. Two other Ca2+ agonists, CGP 28392 and YC-170, also exhibited greater contractions in SHR than in WKY arteries. Increased responsiveness to exogenously added K+ was also observed in the SHR femoral artery. Contractions induced by alpha adrenoceptor stimulation were not different between SHR and WKY. Contractile responses of the SHR femoral artery to Bay k 8644 were antagonized competitively by both nifedipine (pA2 = 8.36) and verapamil (pA2 = 6.77), but noncompetitively by diltiazem. Nifedipine showed a typical competitive antagonism toward Ca2+-indueed contractions in K+-depolarized strips of SHR femoral arteries with a pA2 value of 9.42. These results suggest that: (1) The SHR femoral artery possesses increased Ca2+-handling properties; (2) Bay k 8644 acts primarily on the same site, presumably the voltage-dependent Ca2+ channels at which both nifedipine and verapamil act; and (3) the state of the channel may differ between the stimulation of Bay k 8644 and K+ depolarization.