title: Effect of high extracellular Ca(2+) levels in spontaneously hypertensive rat aorta.
abstract: The release of endothelial relaxing factors has been suggested to be important in modulating the inhibition of the contractile activity caused by the increase in extracellular Ca(2+) concentration in arterial tissue. Since the hypertensive process in spontaneously hypertensive rats (SHR) could be associated with the release of endothelial vasoconstrictor factors (mainly cyclooxygenase-dependent endoperoxides and endothelin-1), we studied the contractile responses to KCl, methoxamine and phenylephrine in different aorta ring preparations (intact, de-endothelized, 10(-5) M indomethacin-treated, 10(-6) M CGS-27830 [meso-1,4-dihydro-5-methoxycarbonyl-2, 6-dimethyl-4-(3-nitrophenyl)-3-pyridine carboxylic acid anhydride]-treated, and treated simultaneously with 10(-5) M indomethacin and 10(-6) M CGS-27830) from SHR and normotensive Wistar Kyoto rats (WKY), at various Ca(2+) concentrations (1.25, 2.5, 5 and 10 mM) in the organ bath. In endothelium-intact preparations from WKY rats we observed a decrease in KCl, methoxamine and phenylephrine contractions with high Ca(2+) concentrations (5 and 10 mM), but in the endothelium-intact preparations from SHR, the increase in extracellular Ca(2+) concentration potentiated methoxamine contractions and caused no change in KCl and phenylephrine contractions. When the endothelium was disrupted in preparations from both WKY rats and SHR, we observed a decrease in KCl and methoxamine contractions with high Ca(2+) concentrations. The decrease in phenylephrine contractions caused by high Ca(2+) concentrations was clear in de-endothelized preparations from WKY rats but slight in de-endothelized preparations from SHR. In all indomethacin- and CGS-27830-treated preparations, and also in the preparations from WKY rats and SHR treated with both drugs, we observed a decrease in all the contractile responses with increased Ca(2+) concentration. Besides, there was a clear reduction in the responses of the alpha(1)-adrenoceptor agonists in the WKY and SHR preparations treated with both drugs. The results indicate that, in the hypertensive arteries, endothelium-derived contractile factors can counteract the relaxing effect of high extracellular Ca(2+) concentrations.
authors.affiliation: Departamento de Farmacología, Facultad de Medicina, Universidad Complutense de Madrid, Ciudad Universitaria s/n 28040, Madrid, Spain.
authors.forename: A O
authors.initials: AO
authors.lastname: Mateo
authors.forename: M A
authors.initials: MA
authors.lastname: de Artiñano
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000503:physiopathology; D002118:Calcium / Q000494:pharmacology*; D004095:Dihydropyridines / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000502:physiology; D006973:Hypertension / Q000503:physiopathology*; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008729:Methoxamine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology
chemical_list: D004095:Dihydropyridines; D014662:Vasoconstrictor Agents; C097746:CGS 27830; D010656:Phenylephrine; D011189:Potassium Chloride; D008729:Methoxamine; D002118:Calcium; D007213:Indomethacin