Changes of cardiac calcium homeostasis in spontaneously hypertensive rats

1 The aim of the present study was to assess the alterations in cardiac Ca2+ homeostasis induced by hypertension using electrically paced right ventricular strips from Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). 2 Basal contractile force was higher in SHR than in WKY. Similarly, the beta-adrenoceptor agonist isoprenaline (10 nM-10 mu M) induced a concentration-dependent positive inotropic effect that was higher in SHR than in WKY, which was in turn inhibited by the beta-adrenoceptor antagonist propranolol (1 mu M) in both strains. 3 Preincubation of strips with the L-type Ca2+ channel blockers, nifedipine (1 mu M) or verapamil (10 mu M), markedly inhibited the isoprenaline response, the inhibition being higher in SHR than in WKY. However, this inhibition was minor by the T-type Ca2+ channel blocker mibefradil (10 mu M). 4 Bay K 8644 (10 nM-10 mu M), a L-type Ca2+ channel activator induced a concentration-dependent positive inotropic effect, that was greater in SHR than WKY. 5 Nifedipine and verapamil (both 0.1 nM-10 mu M) inhibited in a concentration-dependent way the inotropic effect induced by 0.3 mu M isoprenaline or 1 mu M Bay K 8644. The inhibition was higher in SHR than in WKY. Mibefradil (0.1 nM-10 mu M) only clearly inhibited the isoprenaline and Bay K 8644 inotropic effects at 10 mu M in both strains. 6 The inhibitor of the sarcoplasmic reticulum Ca2+ release, ryanodine (10 nM-10 mu M), was a more effective depressor of isoprenaline-induced response in SHR than in WKY. 7 These results suggest that cardiac Ca2+ homeostasis in SHR ventricular strips is altered compared with those of WKY, showing an increased Ca2+ entry through L-type Ca2+ channels and release from sarcoplasmic reticulum; the participation of T-type Ca2+ channels are irrelevant in this tissue.