VASCULAR SMOOTH-MUSCLE CELL POLYPLOIDY AND CARDIOMYOCYTE HYPERTROPHY DUE TO CHRONIC NOS INHIBITION IN-VIVO

To assess the vascular and cardiac response to NO (nitric oxide) synth ase (NOS) blockade in vivo, Wistar-Kyoto rats (WKY) were treated for 3 wk with N-G-nitro-L-arginine methyl ester (L-NAME; 10 mg.kg(-1).day(- 1)). L-NAME treatment induced hypertension that was associated with in creased plasma renin activity. Flow cytometry cell cycle DNA analysis showed that aortic vascular smooth muscle cells (VSMC) from L-NAME-tre ated WKY had a significantly higher polyploid population compared with WKY controls. Using organ bath experiments, we have shown that aortic rings from L-NAME-treated WKY have an increased contractile response to phenylephrine and impaired relaxation to carbachol compared with co ntrol rings. NOS blockade in vivo caused a significant increase in car diac and left ventricular hypertrophy. Northern mRNA analysis of the m yocardium showed that L-NAME treatment caused reexpression of the feta l skeletal alpha-actin isoform without alterations in collagen type I expression, a pattern indicating true hypertrophy of the cardiomyocyte s. These studies provide further insight to confirm that NO deficiency in vivo results in the development of vascular and cardiac hypertroph y.