Redox Modulation of Gi Protein Expression and Adenylyl Cyclase Signaling: Role of Nitric Oxide

Nitric oxide (NO) has been shown to regulate a variety of physiological functions, including vascular tone. The inhibition of NO synthase by N(omega)-nitro-L-arginine methyl ester (L-NAME) has been reported to increase arterial blood pressure. The present studies were undertaken to investigate if the increased blood pressure by L-NAME is associated with enhanced expression of Gi proteins, implicated in the pathogenesis of hypertension. L-NAME was administered orally into Sprague-Dawley rats for a period of 4 weeks. Control rats were given plain tap water only. The systolic blood pressure was enhanced in L-NAME-treated rats as compared with control rats; however, the heart-to-body weight ratio was not different in the two groups. The levels of Gialpha-2 and Gialpha-3 proteins and their mRNA as determined by western and northern blotting, respectively, were significantly augmented in hearts from L-NAME-treated rats, whereas the levels of Gsalpha and Gbeta were unaltered. In addition, the effect of low concentrations of GTPgammaS on forskolin-stimulated adenylyl cyclase activity (receptor-independent functions of Gialpha) was significantly enhanced, whereas the receptor-dependent inhibitions of adenylyl cyclase were completely attenuated in L-NAME-treated rats. Whereas cholera toxin-mediated stimulation of adenylyl cyclase was unaltered in both group of rats, the stimulatory effects of some agonists on adenylyl cyclase activity were diminished in L-NAME-treated rats. These results suggest the implication of NO in the modulation of Gi protein expression and associated adenylyl cyclase signaling.