Previous studies show that elevations in blood pressure induce concomitant increases in both cardiac mass and slow beta-myosin heavy chain (MHC) expression in rodents, whereas caloric restriction of 50% (CR) causes an increase in beta-MHC while modestly lowering blood pressure in normotensive rats. The goals of this study were to 1) determine if beta-MHC expression could be independently regulated by CR and hypertension when these two interventions are combined and 2) determine if CR exerts a lowering of blood pressure in two contrasting models of rodent hypertension. Rodents were assigned to the following groups: 1) normal control (NC); 2) abdominal aortic constriction (Abcon), a model that induces hypertension via renin-angiotensin II; 3) nephrectomy-deoxycorticosterone acetate treatment (DOCA), a model that induces hypertension through increased salt retention; 4) CR; 5) Abcon+CR; 6) DOCA+CR. Results show that both Abcon and DOCA induced significant increases in systemic blood pressures, left ventricular (LV) weight/body weight, and the relative content of beta-MHC compared with NC. When applied in combination with either Abcon or DOCA, CR significantly blunted the changes observed in both systemic blood pressures and LV weight/body weight. In contrast, CR in conjunction with DOCA augmented % beta-MHC expression relative to either DOCA or CR alone. These data suggest 1) caloric restriction exerts a powerful impact on reducing experimentally induced hypertension in rodents and 2) the regulation of beta-MHC expression appears to be regulated by at least two processes, one associated with the stimulus of hypertension and the other involving an independent pathway linked to caloric restriction.