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 ventri cular strips from Wistar-Kyoto (WKY) and spontaneously hypertensive rats (S HR). 2 Basal contractile force was higher in SHR than in WKY. Similarly, the bet a-adrenoceptor agonist isoprenaline (10 nM-10 mu M) induced a concentration -dependent positive inotropic effect that was higher in SHR than in WKY, wh ich 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 respo nse, the inhibition being higher in SHR than in WKY. However, this inhibiti on 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 con centration-dependent positive inotropic effect, that was greater in SHR tha n WKY. 5 Nifedipine and verapamil (both 0.1 nM-10 mu M) inhibited in a concentrati on-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 ino tropic effects at 10 mu M in both strains. 6 The inhibitor of the sarcoplasmic reticulum Ca2+ release, ryanodine (10 n M-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 st rips 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.