ALTERED EXPRESSION OF G-PROTEIN MESSENGER-RNA IN SPONTANEOUSLY HYPERTENSIVE RATS

We have recently demonstrated that the decreased ability of hormones, forskolin and GTP to stimulate adenylate cyclase in heart and aorta from spontaneously hypertensive rats (SHR), as compared to their age-matched Wistar-Kyoto control rats (WKY), was associated with enhanced levels of Gi- and not with Gs-regulatory proteins. In the present studies we have investigated the expression of Gi-regulatory proteins at the mRNA level by Northern blotting. Total RNA of heart ventricle and aorta from WKY and SHR was probed with radiolabeled cDNA inserts encoding Gialpha-2 and Gialpha-3. The Gialpha-2 and Gialpha-3 probes detected a message of 2-3 and 3-5 kb, respectively, in both WKY and SHR, however, the message was significantly enhanced in SHR, as compared by WKY. On the other hand the cDNA probe encoding Gs(alpha) detected a message of 1.8 kb in heart and aorta from both WKY and SHR, however, no difference in the levels of Gs(alpha) mRNA was detected in SHR and WKY tissues. These results indicate that the mRNA levels of Gialpha-2 and Gialpha-3 and not of Gs are overexpressed in heart and aorta from SHR, which may be responsible for the increased levels of Gi as shown earlier by immunoblotting techniques. It may be suggested that the enhanced vascular tone and impaired cardiac contractility in hypertension may partly be the consequences of increased levels of Gi in heart and aorta.