Nitric oxide synthase inhibition by L-NAME modulates G-protein expression and adenylyl cyclase activity in rat heart.

We have recently shown an enhanced expression of Giα2 and Giα3 protein and mRNA in hearts from DOCA-salt hypertensive rats, however, it is not known whether these changes are due to the expressed hypertrophy or hypertension. The present studies were therefore undertaken to investigate this possibility. Hypertension, in Sprague-Dawley rats, was induced by the oral administration of the arginine analog, L-NAME, in their drinking tap water for a period of 4 weeks, whereas the control rats were given plain tap water only. The rats were sacrificed and the hearts were removed for adenylyl cyclase activity determination and G-protein content. L-NAME-treated rats showed an enhanced blood pressure (190 ± 9.25 mm Hg) as compared to control rats (121 ± 6.3 mm Hg), however, heart to body weight ratio was not different in the two groups. GTPγS, stimulated adenylyl cyclase activity in heart membranes from both groups, however, the extent of stimulation was significantly decreased in L-NAME-treated rats. Similarly, the stimulatory effects of isoproterenol, glucagon, NECA, NaF and forskolin were also diminished in L-NAME-treated rats. On the other hand, the inhibitory effect of low concentration of GTPγS on forskolin-stimulated enzyme activity was significantly enhanced. The levels of Giα-2 and Giα-3, but not of Gsα and Gβγ, as determined by immunoblotting, was significantly augmented in L-NAME treated rats. These results suggest that the enhanced expression of Giα proteins and associated functions in L-NAME-treated rats may be attributed to hypertension and not to hypertrophy.