Lovastatin prevents development of hypertension in spontaneously hypertensive rats.
The present study evaluated the effects of lovastatin on renal function and the development of hypertension in spontaneously hypertensive rats (SHR). Four-week-old SHR were given lovastatin (10 mg/kg) or vehicle twice daily by gavage. After 4 weeks of treatment, mean arterial pressure was significantly lower in lovastatin-treated SHR (131 +/- 4 mm Hg, n=5) than in control animals (160 +/- 4 mm Hg, n=12) (P<.05). The fall in arterial pressure in lovastatin-treated rats was accompanied by changes in renal function. The slope of the relationship between arterial pressure and sodium excretion was threefold greater in lovastatin-treated SHR (n=6) than in control rats (n=6), and this was associated with significant elevations in renal medullary blood flow and renal interstitial hydrostatic pressure. Glomerular filtration rate was 17% higher in lovastatin-treated SHR (n=6) than in control rats (n=6) (0.94 +/- 0.05 versus 0.81 +/- 0.07 mL/min per g of kidney weight, P<.05). The wall-to-lumen area ratio of renal arterioles was significantly reduced in lovastatin-treated SHR compared with vehicle-treated rats (0.86 +/- 0.05 versus 1.08 +/- 0.04 for vessels with inner diameters <50 microm and 0.62 +/- 0.02 versus 0.75 +/- 0.04 for vessels with inner diameters of 50 to 100 microm, P<.05). These results indicate that chronic treatment with lovastatin shifts the relations between renal medullary blood flow, renal interstitial pressure, sodium excretion, and renal perfusion pressure to lower levels of arterial pressure and attenuates the development of hypertension and renal vascular hypertrophy in SHR.
Jiang
J
J
Department of Physiology, Medical College of Wisconsin, Milwaukee 53226, USA.
Roman
R J
RJ
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001160:Arterioles / Q000473:pathology; D001794:Blood Pressure / Q000187:drug effects; D005110:Extracellular Space / Q000502:physiology; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006830:Hydralazine / Q000494:pharmacology; D006874:Hydrostatic Pressure; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D006973:Hypertension / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D007668:Kidney / Q000187:drug effects / Q000503:physiopathology; D007679:Kidney Medulla / Q000098:blood supply; D008148:Lovastatin / Q000494:pharmacology*; D009318:Natriuresis / Q000187:drug effects; D051381:Rats; D011918:Rats, Inbred SHR / Q000502:physiology*; D012079:Renal Circulation / Q000187:drug effects
D000959:Antihypertensive Agents; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D006830:Hydralazine; D008148:Lovastatin