Abstract 31: Improvement of Salt-sensitive hypertension in SS-Mstnem1Mcwi Rats
Hypertension afflicts nearly 1/3rd of American adults but exercise is known to help lower blood pressure by mechanisms which are not well-understood. Exercise increases muscle mass, which might in turn improve metabolism or lower peripheral resistance to improve blood pressure. To determine the effects of increased muscle mass on blood pressure regulation, pressure was monitored via telemetry in salt-sensitive rats in which myostatin (SS-Mstn) had been targeted for disruption by zinc finger nuclease technology through the PhysGen Knockouts program at the Medical College of Wisconsin. At 24-26 weeks of age, SS-Mstn were heavier (430+20 vs. 363+20, p<0.05) with larger muscles (gastrocnemius, 60%, gluteus maximus, 30%) compared to SS-controls. Body length was similar. At baseline on 0.4% salt diet, blood pressure was higher in SS-control (161+4 vs. 123+8 mm Hg, p<0.05) compared to SS-Mstn. When salt was elevated to 4%, the pressure increase was smaller in SS-Mstn (5+1 vs 14+3 mm Hg, p<0.05). Lowering dietary salt to 0.1% caused a larger drop in SS-control than SS-Mstn (19+6 vs. 3+2, p<0.05). Heart rate was similar on normal and low salt conditions but slightly higher in SS-control on high salt diet. In parallel, kidney mass was lower in SS-Mstn (1.4+0.1 vs 1.8+0.3, p<0.05) and peak responses to acetylcholine in aortic rings were larger in SS-Mstn (57+3 vs. 35+7 %, p<0.05). Vasoconstrictor responses to phenylephrine and serotonin were similar between groups as was vasodilation to nitroprusside. Taken together, these data suggest that an increase in muscle mass or a loss of myostatin signaling is of significant benefit in the regulation of arterial pressure. This may reflect improvements in vasodilator function but more extensive studies are needed to fully determine the mechanism of the blood pressure lowering effect.
- © 2012 by American Heart Association, Inc.