Enhanced Expression of G(alpha)q and PLCβ1 in Aortic Vascular Smooth Muscle Cells from Spontaneously Hypertensive Rats: Role of Endogenous Angiotensine II and Endothelin‐1

Abstract

Gαq and Gαq associated signaling play an important role in the regulation of vascular tone and cardiac hypertrophy. We have earlier shown that hyperglycemia, induced enhanced expression of Gαq and PLCβ proteins in vscular smooth muscle cells (VSMC) which was attributed to the endogenous levels of angiotensin II (Ang II) and endothelin‐1 (ET‐1). The present study was undertaken to investigate if the expression of Gαq and PLCβ1 proteins is upregulated in aortic VSMC from 16 week‐old spontaneously hypertensive rats (SHR) that has been shown to exhibit cardiac hypertrophy and to further explore the implication of endogenous Ang II and ET‐1 in this upregulation. The expression of Gαq and PLCβ proteins in VSMC was determined by Western Blotting analysis, whereas vascular hypertrophy and prolifeartion was determined by 3H‐leucine and 3H‐thymidine incorporation respectively. The expression of Gαq and PLCβ1 proteins was significantly increased in VSMC from 16‐week old SHR and not from 12‐week old SHR as compared to their age mached WKY rats. The incresead expression of Gαq and PLCβ1 was attenuated by AT1 receptor antagonist, losartan, and ETA receptor antagonist, BQ123, but not by ETB receptor antagonist, BQ788. Protein and DNA synthesis was significantly augmented in VSMC from 16 week‐old SHR as compared to WKY rats. However, the antisense of Gαq attenuated the hypertrophy but not the prolifeartion. These results suggest that VSMC from 16‐week old SHR exhibit enhanced expression of Gαq and PLCβ1 which may be attributed to enhanced levels of Ang II and ET‐1 and may be responsible for the vascular hypertrophy observed in 16 week‐ald SHR.