Effects of oxodipine on isolated rabbit aorta and mesenteric resistance vessels

The inhibitory effects of the dihydropyridine Ca2+ antagonist, oxodipine, on contractions and 45Ca2+ influx stimulated by noradrenaline (NA) and high K+ in rabbit aorta were compared to the same parameters measured in mesenteric resistance arteries. In aortic rings oxodipine, 10(-11)-10(-6) M, inhibited in a concentration-dependent manner the contractions induced by high K+ (IC50 = 9.0 +/- 4.0 x 10(-10) M) or by Ca2+ in high K+ solution (IC50 = 6.2 +/- 2.4 x 10(-9) M), while responses to NA were only slightly affected (IC50 greater than 10(-6) M). In mesenteric resistance vessels oxodipine inhibited the contractions induced by high K+ and NA but was more effective against NA- than high K(+)-induced contractions (IC50 = 5.2 +/- 3.1 x 10(-10) and 1.2 +/- 1.8 x 10(-8) M, respectively). The concentration-inhibition curves for high K(+)-induced contraction and 45Ca2+ influx in aorta were almost superimposable (I50 = 2.2 +/- 2.0 x 10(-9) M), whereas NA-induced contractions were inhibited less than 45Ca2+ influx (I50 = 8.2 +/- 2.6 x 10(-8) M). In mesenteric resistance vessels the curves for contraction and 45Ca2+ influx stimulated by high K+ and NA were also superimposable, but 45Ca2+ influx stimulated by NA was more sensitive to oxodipine than that stimulated by high K+ (I50 = 3.9 +/- 2.0 x 10(-10) and 2.2 +/- 1.2 x 10(-8) M, respectively). It is concluded that the effects of oxodipine can be attributed to its ability to inhibit Ca2+ entry through both potential- and receptor-operated pathways.(ABSTRACT TRUNCATED AT 250 WORDS)