Modulation of G-protein expression by the angiotensin converting enzyme inhibitor captopril in hearts from spontaneously hypertensive rats : Relationship with adenylyl cyclase

We have recently shown an enhanced expression of Giα-2 and Giα-3 at protein and mRNA levels and their relationship with adenylyl cyclase regulation in hearts and aorta from spontaneously hypertensive rats (SHR). The present studies were undertaken to examine if the antihypertensive action of captopril, an angiotensin I converting enzyme (ACE) inhibitor, is associated with the interaction and modulation of G-proteins and adenylyl cyclase activity. SHR and age-matched WKY were divided into two groups. One group of rats received captopril (10 mg/kg body weight) intravenously, whereas the other group received only vehicle (0.9% saline). The levels of Giα-2 and Giα-3 proteins were determined by immunoblotting technique using specific antisera against these proteins. The levels of Giα-2 and Giα-3 proteins were significantly enhanced in hearts from SHR as compared to WKY and captopril treatment restored the enhanced levels of Giα-2 and Giα-3 observed in SHR by about 70% to 80% towards WKY control rats. However, captopril slightly decreased the levels of Giα2 and Giα3 protein in normotensive WKY. In addition, the diminished stimulation of adenylyl cyclase by isoproterenol, glucagon and N-ethyl carboxamide adenosine and enhanced inhibition by inhibitory hormones such as C-type natriuretic peptide and angiotensin II observed in SHR was restored significantly by captopril treatment. These results suggest that one of the mechanisms by which captopril lowers the blood pressure may be due to its ability to modulate the levels of G-proteins and adenylyl cyclase activity.