title: Changes of cardiac calcium homeostasis in spontaneously hypertensive rats.
abstract: 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 microM) 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 microM) in both strains. 3 Preincubation of strips with the L-type Ca2+ channel blockers, nifedipine (1 microM) or verapamil (10 microM), 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 microM). 4 Bay K 8644 (10 nM-10 microM), 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 microM) inhibited in a concentration-dependent way the inotropic effect induced by 0.3 microM isoprenaline or 1 microM Bay K 8644. The inhibition was higher in SHR than in WKY. Mibefradil (0.1 nM-10 microM) only clearly inhibited the isoprenaline and Bay K 8644 inotropic effects at 10 microM in both strains. 6 The inhibitor of the sarcoplasmic reticulum Ca2+ release, ryanodine (10 nM-10 microM), 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.
authors.affiliation: Departamentos de Farmacología y Terapéutica, Madrid, Spain.
authors.forename: A M
authors.initials: AM
authors.lastname: Manso
authors.forename: A
authors.initials: A
authors.lastname: Encabo
authors.forename: M
authors.initials: M
authors.lastname: Ferrer
authors.forename: G
authors.initials: G
authors.lastname: Balfagón
authors.forename: M
authors.initials: M
authors.lastname: Salaices
authors.forename: J
authors.initials: J
authors.lastname: Marín
mesh_terms: D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002120:Calcium Channel Agonists / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000145:classification / Q000187:drug effects; D004558:Electric Stimulation; D006352:Heart Ventricles / Q000187:drug effects; D006706:Homeostasis / Q000502:physiology*; D006973:Hypertension / Q000378:metabolism*; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D020748:Mibefradil / Q000494:pharmacology; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000378:metabolism*; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012433:Ryanodine / Q000494:pharmacology
chemical_list: D002120:Calcium Channel Agonists; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D012433:Ryanodine; D020748:Mibefradil; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D011433:Propranolol; D007545:Isoproterenol; D002118:Calcium