GUANINE-NUCLEOTIDE-BINDING PROTEINS IN AORTIC SMOOTH-MUSCLE FROM HYPERTENSIVE RATS

To explore the hypothesis that altered vascular muscle signal transduction may underlie some of the vascular changes observed in hypertensive models, we measured expression of GTP-binding protein (G protein) alpha-subunits, G(s), G(i), and G(q), in aortic muscle of reduced renal mass and sham-operated rats and proximal and distal aortic segments from rats with interrenal aortic coarctation (IR-AC). G protein expression was measured by immunoblot analysis. When we probed aortic muscle membrane with G(i) and G(q) alpha-subunit antibodies, we identified 41- and 42-kD immunoreactive proteins, respectively. Three immunoreactive bands specific to G(s) alpha-subunit antibody were resolved. Immunoreactive blot densities were compared. In aortic muscle membrane of reduced renal mass rats (blood pressure, 148+/-7 mm Hg), we found significantly reduced G(s) and G(i) blot densities compared with sham-operated controls (blood pressure, 99+/-12 mm Hg). There were no differences in G(q) blot densities between reduced renal mass and control rats. G(s) and G(i) blot densities were significantly lower in IR-AC proximal aortic segments (carotid pressure, 165+/-5 mm Hg) and distal aortic segments (femoral pressure, 121+/-4 mm Hg) than in aortas of sham-operated controls. In contrast, G(q) expression was significantly increased in the high-pressure proximal aortic segments compared with low-pressure distal aortic segments from IR-AC rats. Thus, altered G protein expression occurs in aortic muscle from nongenetic rat models of hypertension. Given the differences between reduced renal mass and IR-AC models, it is clear that pressure is not the only variable regulating G protein expression and that hormonal and/or metabolic influences probably play a larger role.