Effects of dihydropyridines on tension and calcium-45 influx in isolated mesenteric resistance vessels from spontaneously hypertensive and normotensive rats

Abstract

Contractile tension responses to norepinephrine and depolarizing potassium (80 mM K +), as well as calcium-45 influx stimulated by these agents, were studied in isolated mesenteric resistance vessels (each 100 μM internal diameter) from spontaneously hypertensive rats (SHRs) and from normotensive Wistar Kyoto rats (WKYs). Inhibitory effects of 2 dihydropyridine Ca ++ antagonists, PN 200-110 (isradipine) and nisoldipine, on these parameters were also determined. Contractile responses to 80 mM K + were inhibited by both Ca ++ antagonists with the same potency and efficacy in SHR compared with WKY vessels (PN 200-110 IC 50 = 2.8 ± 1.3 × 10 −8 M in SHRs and 2.5 ± 1.5 × 10 −8 M in WKYs; nisoldipine IC 50 = 1.1 ± 0.4 × 10 −8 M in SHRs and 1.2 ± 0.9 × 10 −8 M in WKYs). However, contractile responses to norepinephrine (10 −4 M) were inhibited less potently by nisoldipine in SHR vessels (IC 50 = 2.2 ± 0.3 × 10 −9 M) compared with WKY vessels (IC 50 = 1.6 ± 0.6 × 10 −10 M). Similarly, PN 200-110 tended to be less (but not significantly less) potent in SHR vessels (IC 50 = 3.3 ± 1.8 × 10 −8 M) than in WKY vessels (IC 50 = 3.4 ± 0.9 × 10 −9 M); its efficacy was significantly depressed in the SHR vessels (by approximately 20%). When norepinephrine-stimulated calcium-45 influx was determined in the presence of these Ca ++ antagonists, a similar profile emerged with respect to a comparison of SHR and WKY vessels. These results support a previously hypothesized alteration in receptor-activated Ca ++ influx pathways in SHR mesenteric resistance vessels.