Decreased Phorbol Ester-Induced Inhibition of Inositol Trisphosphate Formation Mediated by Alpha1-Adrenoceptors in Myocytes of Spontaneously Hypertensive Rats

Alpha1-adrenoceptors, norepinephrine(NE)-stimulated formation of inositol trisphosphate (IP3) and inhibitory effect on this formation by 12-o-tetradecanoyl phorbol 13-acetate (TPA) were studied in isolated myocytes of 8-week-old spontaneously hypertensive rat (SHR) and Wistar-Kyoto rat (WKY). The number of alpha1-adrenoceptors in myocytes of SHR was significantly increased than that of WKY. No significant difference in maximum response or EC50 values of NE-stimulated IP3 formation was observed between the two strains. Both norepinephrine-stimulated and GTPyS-stimulated IP3 formation was inhibited by TPA. The inhibitory effect was less in SHR than in WKY. PA did not change the number and affinity of alphal-adrenoceptors. These results suggest that myocytes of SHR may have abnormality in G protein and/or phospholipase C and that activation of protein kinase C might inhibit IP3 formation less in SHR than in WKY, a step distal to alphal -adrenoceptors, probably at a step distal to alphal -adrenoceptors.