Abstract
The calcium-channel blocking action of franidipine (CV-4093·2HCl) was investigated in vitro and in vivo. CV-4093·2HCl inhibited the 60 mM K+-induced contraction of rabbit aorta and those of coronary, renal, mesenteric and femoral arteries of dog less potently than nifedipine and nicardipine. In dog portal and femoral veins, CV-4093·2HCl inhibited K+-induced contraction as potently as nifedipine and nicardipine did. The inhibitory effect of this drug was fully developed by pretreatment for 60 min, and it lasted long after washout. The drug inhibited both K+-induced 45Ca-influx and K+-induced contraction at a similar concentration range in rabbit aorta and dog portal vein, but had no effect on 45Ca-efflux from either vessel. On the other hand, in the isolated, perfused kidneys and mesenteric vascular beds of SHR, CV-4093·2HCl inhibited K+-induced vasoconstriction more effectively than did nifedipine. Moreover, in pithed rats (i.v.) and ganglion-blocked conscious SHR (p.o.), CV-4093·2HCl inhibited more potently α2-adrenergic pressor responses than did nicardipine. These pharmacological properties of CV-4093·2HCl, especially those seen in the isolated, perfused kidney and mesenteric vascular beds, may be responsible for its potent and long-lasting action as an antihypertensive agent.
