Effect of high extracellular Ca 2+ levels in spontaneously hypertensive rat aorta

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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 α 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.