COMPARATIVE-STUDY OF ELGODIPINE AND NISOLDIPINE ON THE CONTRACTILE RESPONSES OF VARIOUS ISOLATED BLOOD-VESSELS

The effects of elgodipine, a new dihydropyridine derivative, were comp ared to those of nisoldipine on contractile responses in various isola ted artery rings and on mechanical activity in portal vein segments. A rteries used were: rabbit aorta, mesenteric (fifth branch), femoral an d basilar, and sheep coronary arteries. Elgodipine and nisoldipine (10 (-16)-3 X 10(-6) M) produced a concentration-dependent inhibition of t he contractile responses induced by high K+ (80 mM), 5-hydroxytryptami ne (10(-5) M) or noradrenaline (10(-6) M or 10(-4) M) in all the arter ies studied. The inhibitory effect of elgodipine was greater in mesent eric resistance vessels (IC50 = 8.0 +/- 2.1 x 10(-12) M and 2.0 +/- 0. 5 x 10(-13) M for the depression of high K+- and agonist-induced contr action, respectively), and in coronary arteries (IC50 = 2.6 +/- 0.3 x 10(-10) M and 9.0 +/- 1.4 x 10(-8) M for the inhibition of high K+-and agonist-induced contraction, respectively). In addition, the action o f elgodipine in peripheral resistance vessels and in the coronary arte ry was more prominent than in aorta or femoral arteries, and this tiss ue selectivity was more apparent for elgodipine than for nisoldipine. In rat portal vein elgodipine (IC50 = 6.5 +/- 0.9 X 10(-8) M) and niso ldipine (IC50 = 6.5 +/- 1.3 X 10(-8) M) reduced in a concentration-dep endent manner the development of mechanical activity. Furthermore, con tractile responses produced by the addition of Ca2+ (1-5 mM) to Ca2+-f ree high K+ solution were also concentration dependently inhibited by elgodipine. However, elgodipine did not modify noradrenaline-induced c ontractions attributed to intracellular Ca2+ release. The results of t his study indicate that elgodipine has potent vasodilator properties a nd vascular selectivity. The mechanisms through which elgodipine relax es vascular smooth fibres seem to be related to its ability to inhibit the entry of extracellular Ca2+ into the cell.