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 could influence BP and renal function in hypertension. To test this issue, transit-time ultrasound flow probes, implanted optical fibers, and laser-Doppler 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) chronically treated deoxycorticosterone acetate (DOCA)-salt hypertensive mice. Total renal blood flow was well autoregulated between 70 and 150 mmHg (approximately 3.5 ml/min per g kidney weight in DOCA-salt mice). Both lovastatin 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 investigated, 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 baseline values, which was not seen in vehicle- or bezafibrate-treated mice. After extracellular volume expansion with 1% saline, 1 ml over 1 min, total renal blood flow was also higher in lovastatin- or bezafibrate-treated DOCA-salt mice, whereas medullary blood flow increased more steeply in lovastatin-, compared with bezafibrate- or vehicle-treated mice. Systemic BP was significantly decreased in lovastatin-treated DOCA-salt mice compared with vehicle-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. Finally, lovastatin decreased systemic BP in DOCA-salt mice. These data suggest that cholesterol synthesis inhibition or fibrate treatment improve disturbed renal function in a mouse model of salt-dependent hypertension.
Franz Volhard Clinic and Max Delbrück Center for Molecular Medicine, Medical Faculty of the Charité, Humboldt University of Berlin, Germany.
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Gross
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Schneider
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Schunck
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Mervaala
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Luft
D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology; D001629:Bezafibrate / Q000494:pharmacology*; D001783:Blood Flow Velocity / Q000187:drug effects; D003900:Desoxycorticosterone / Q000633:toxicity; D004231:Diuresis / Q000187:drug effects; D006973:Hypertension / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D007672:Kidney Cortex / Q000098:blood supply / Q000187:drug effects / Q000473:pathology; D007679:Kidney Medulla / Q000098:blood supply / Q000187:drug effects / Q000473:pathology; D008148:Lovastatin / Q000494:pharmacology*; D051379:Mice; D011312:Pressure; D012079:Renal Circulation / Q000187:drug effects*; D014655:Vascular Resistance / Q000187:drug effects
D000924:Anticholesteremic Agents; D000960:Hypolipidemic Agents; D003900:Desoxycorticosterone; D008148:Lovastatin; D001629:Bezafibrate