G-PROTEIN MESSENGER-RNA EXPRESSION IN RENAL MICROVESSELS FROM SPONTANEOUSLY HYPERTENSIVE AND WISTAR-KYOTO RATS

The exaggerated sensitivity of spontaneously hypertensive rat (SHR) re nal microvasculature to angiotensin II (ANG II) may be due to an imbal ance between the effectiveness of Ga,utilizing vasodilator pathways an d vasoconstrictor pathways activated by ANG II (mediated by G alpha(i- 1), G alpha(i-2), G alpha(i-3), and G alpha(q)). Because the alteratio n appears to be distal to the hormone receptors and proximal to the ef fector adenylyl cyclase, we hypothesized that SHR have altered amounts of signal-transducing G proteins. This was examined by quantifying th e steady-state mRNA levels of specific G alpha subunits in renal micro vessels of 12- to 14-wk-old SHR and control Wistar-Kyoto (WKY) rats, u sing a quantitative-competitive polymerase chain reaction technique co upled to reverse transcription. No significant differences were detect ed in the absolute levels of G alpha(s) (0.96 +/- 0.35 vs. 0.74 +/- 0. 25 amol/50 ng RNA) or in the relative levels of G alpha(i-1) (0.44 +/- 0.05 vs. 0.48 +/- 0.13), G alpha(i-2) (40.9 +/- 7.8 vs. 45.2 +/- 8.9) , or G alpha(i-3) (0.79 +/- 0.05 vs. 0.82 +/- 0.15) normalized to the level of Ga, for WKY vs. SHR, respectively. The ratio of G alpha(q) to G alpha(s) tended to be higher in SHR, but this difference did not ac hieve statistical significance (0.41 +/- 0.08 vs. 1.04 +/- 0.32, P = 0 .08). In conclusion, the steady-state levels of G alpha(s), G alpha(i- 1), G alpha(i-2), G alpha(i-3), and G alpha(q) are similar in SHR and WKY renal microvasculature, suggesting that other components of the AN G II signal transduction mechanism are responsible for the enhanced re nal vascular responsiveness in SHR.