Effects of oxodipine on isolated rabbit aorta and mesenteric resistance vessels

Abstract

The inhibitory effects of the dihydropyridine Ca 2+ antagonist, oxodipine, on contractions and 45Ca 2+ influx stimulated by noradrenaline (NA) and high K + in rabbit aorta were compared to the same parameters measured in mesentric resistance arteries. In aortic rings oxodipine, 10 −11−10 −6 M, inhibited in a concentration-dependent manner the contractions induced by high K + (IC 50 = 9.0±4.0×10 −10M) or by Ca 2+ in high K + solution (IC 50 = 6.2±2.4×10 −9M), while responses to NA were only slightly affected (IC 50>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 (IC 50 = 5.2±3.1×10 −10 and 1.2±1.8×10 −8 M respectively). The concentration-inhibition curves for high K +-induced contraction and 45Ca 2+ influx in aorta were almost superimposable (I 50 = 2.2±2.0×10 −9 M), whereas NA-induced contractions were inhibited less than 45Ca 2+ influx (I 50 = 8.2±2.6×10 −8 M), In mesentric resistance vessels the curves for contraction and 45Ca 2+ influx stimulated by high K + and NA were also superimposable, but 45Ca 2+ influx stimulated by NA was more sensitive to oxodipine than that stimulated by high K + (I 50 = 3.9±2.0×10 −10 and 2.2±1.2×10 −8 M, respectively). It is concluded that the effects of oxodipine can be attributed to its ability to inhibit Ca 2+ entry through both potential- and receptor-operated pathways. The higher sensitivity of NA-induced contraction and 45Ca 2+ influx in mesenteric resistance vessels to oxodipine as compared to aorta may be related not only to the fact that the contraction induced by NA in resistance vessels is nearly completely dependent on extracellular Ca 2+ but also to the high sensitivity of their NA-activated Ca 2+ entry.