FIG. 5.

Smooth muscle-targeted expression of RhoA^A188 augments vascular ROCK activity, hypertrophy, and fibrosis and imparts unresponsiveness to the inhibitory effect of BNP. NTg, RhoA^WT-Tg, RhoA^A188-Tg, BNP-Tg, RhoA^WT/BNP-Tg, and RhoA^A188/BNP-Tg mice were compared for analysis. (A) (Left) Bar graphs showing ROCK activity in the aortas (n = 3). (Right) Fraction of incremental ROCK activity in RhoA^WT-Tg and RhoA^A188-Tg aortas over NTg aortas that is inhibitable by crossbreeding with BNP-Tg mice. The original blot image is found in Fig. S2B in the supplemental material. (B) Systolic BPs (sBP) of mice (n = 5 to 11). (C and D) Morphological assessment of coronary arteries (n = 25 to 53). (C) Representative Sirius red staining of heart sections. Bar, 50 μm. (D) (Left) Morphometric analysis of coronary artery MT (top) and PVF (bottom). The MT and PVF were determined as described in the legend for Fig. 2. (Right) Fraction of incremental MT (top) and PVF (bottom) of RhoA^WT-Tg or RhoA^A188-Tg coronary arteries over NTg coronary arteries that is inhibitable by crossbreeding with BNP-Tg mice. In panels A and D, the BNP inhibitability of the myc-RhoA-induced increase in the indicated parameter was corrected for the baseline effect of BNP by the following formula: BNP inhibitability (%) = [(RhoA^x-Tg value − RhoA^x/BNP-Tg value) − (NTg value − BNP-Tg value)]/(RhoA^x-Tg value − NTg value), where x is WT or A188. Values are means ± SEM. *, P < 0.05; **, P < 0.01; #, P < 0.001; NS, not significant.