Altered pineal adrenergic-stimulated cyclic nucleotide responses in spontaneously hypertensive rats

In this study, we examined the pineal adrenergic-stimulated cyclic nucleotide responses in spontaneously hypertensive rats (SHR) and their genetic control, Wistar-Kyoto rats (WKY). Treatment with norepinephrine stimulated cAMP and cGMP contents up to 50- and 12-fold in WKY pinealocytes, compared with a 35- and 4-fold increase in SHR. By contrast, there was no difference in the isoproterenol-stimulated cAMP and cGMP contents, suggesting a reduced alpha 1-adrenergic potentiation of beta-adrenergic-stimulated cGMP response in SHR pinealocytes. The altered potentiation mechanism was examined using agents that activate protein kinase C or elevate intracellular Ca2+. In the presence of a protein kinase C activator, the isoproterenol-stimulated cAMP response was potentiated to a similar degree in WKY and SHR pinealocytes. In contrast, the potentiating effects of ionomycin and KCl on the isoproterenol-stimulated cAMP and cGMP responses in SHR pinealocytes were markedly reduced. These results indicate that in the SHR pineal gland, an altered intracellular Ca(2+)-mediated event may account for the reduction in alpha 1-adrenergic potentiation of beta-adrenergic-stimulated cyclic nucleotide responses.