Enhanced expression of Giα protein and adenylyl cyclase signaling in aortas from 1 kidney 1 clip hypertensive ratsThis paper is one of a selection of papers published in this Special issue, entitled Second Messengers and Phosphoproteins—12th International Conference.

Abstract

We have previously shown the augmented levels of Giα-2 and Giα-3 proteins (isoforms of inhibitory guanine nucleotide regulatory protein (G-protein)), and not of Gsα, in the hearts and aortas of spontaneously and experimentally induced hypertensive rats. The increased expression of Giα and blood pressure was restored toward WKY levels by captopril treatment, suggesting a role for angiotensin (Ang) II in the enhanced expression of Giα protein and blood pressure. This study was undertaken to investigate whether 1 kidney 1 clip (1K-1C) hypertensive rats that exhibit enhanced levels of Ang II also express enhanced levels of Giα proteins. Aortas from 1K-1C hypertensive rats were used. The expression of G-proteins was determined at protein levels with immunoblotting techniques, using specific antibodies for different isoforms of G-proteins. The levels of Giα-2 and Giα-3 proteins were significantly higher in aortas from 1K-1C hypertensive rats than in control rats; Gsα levels were unchanged. The inhibitory effect of low concentrations of guanosine 5′-[γ-thio]triphosphate (GTPγS) on forskolin (FSK)-stimulated adenylyl cyclase (AC) activity was significantly enhanced in aortas from 1K-1C hypertensive rats; the inhibitory effect of C-ANP4–23, which specifically interacts with the atrial natriuretic peptide (ANP)-C receptor, and Ang II on AC was attenuated. GTPγS, isoproterenol, glucagon, NaF, and FSK stimulated the AC activity in aortas from control and hypertensive rats to varying degrees; however, the stimulations were significantly lower in hypertensive rats than in control rats. These data suggest that aortas from 1K-1C hypertensive rats exhibit enhanced expression of Giα proteins and associated functions.