Hypertension in Transgenic Mice Expressing the Rac-1 Protein in Vascular Smooth Muscle

46 A novel transgenic mice has been generated which overexpresses the constitutively activated mutant form of human Rac 1 (Rac-CA), a small GTP-binding protein of the Rho family, in smooth muscle cells. Experiments were conducted to determine whether chronic activation of Rac-1 affects blood pressure (BP) and heart rate (HR). Male Rac-CA and control mice were prepared for chronic cardiovascular monitoring using carotid arterial catheters infused with heparinized saline. BP and HR were measured continuously for more than 4 days. Results show an increased BP in Rac-CA with no change in HR or water intake. BP was consistently higher in Rac-CA mice (Figure), averaging 122±4 vs 109±4 mm Hg during the dark phase (Rac-CA vs Control). HR showed a night/day rhythm with no differences between the Rac-CA and Controls, respectively, 640±15 vs 610±11 bpm (dark) and 572 ±39 vs 578 ±18 (light). These results illustrate that alteration in intracellular signaling (reactive oxygen species) in vascular smooth muscle produces changes in blood pressure. The mild to moderate hypertension observed in this animal model is similar to the human condition.