Chronic effects of lovastatin and bezafibrate on cortical and medullary hemodynamics in deoxycorticosterone acetate-salt hypertensive mice

Cholesterol synthesis inhibitors and fibrates both exercise effects that co uld influence BP and renal function in hypertension. To test this issue, tr ansit-time ultrasound flow probes, implanted optical fibers, and laser-Dopp ler flowmetry were used for measurements of total and regional renal blood flows in lovastatin (40 mg/kg body wt) and bezafibrate (50 mg/kg body wt) c hronically treated deoxycorticosterone acetate (DOCA)-salt hypertensive mic e. Total renal blood flow was well autoregulated between 70 and 150 mmHg (a pproximately 3.5 ml/min per g kidney weight in DOCA-salt mice). Both lovast atin and bezafibrate increased renal blood flow to a range between 4.7 and 5.5 ml/min per g kidney weight. In the renal perfusion pressure ranges inve stigated, renal vascular resistance increased in lovastin- and bezafibrate- treated DOCA-salt mice, but not as steeply as in vehicle-treated DOCA-salt mice. During a stepwise increase in renal perfusion pressure in lovastatin- treated DOCA-salt mice, medullary blood flow increased up to 130% of baseli ne values, which was not seen in vehicle- or bezafibrate-treated mice. Afte r extracellular volume expansion with 1% saline, 1 mi over 1 min, total ren al blood new was also higher in lovastatin- or bezafibrate-treated DOCA-sal t mice, whereas medullary blood flow increased more steeply in lovastatin-, compared with bezafibrate- or vehicle-treated mice. Systemic BP was signif icantly decreased in lovastatin-treated DOCA-salt mice compared with vehicl e-treated mice. Lovastatin prevented histologic evidence for hemostasis in the medullary circulation of DOCA-salt mice. The results suggest that both lovastatin and bezafibrate diminished DOCA-salt-induced reductions in total renal blood flow. Lovastatin also abolished the perturbed medullary blood flow reactions to increased perfusion pressure or to volume expansion. Fina lly, lovastatin decreased systemic BP in DOCA-salt mice. These data suggest that cholesterol synthesis inhibition or fibrate treatment improve disturb ed renal function in a mouse model of salt-dependent hypertension.