Losartan prevents salt-induced hypertension in reduced renal mass rats.
A reduction in functioning renal mass through surgical ablation leads to the development of hypertension and chronic renal failure in rats. Reduced renal mass (RRM) hypertension is more severe and develops more quickly if rats are on high salt intake. It has previously been shown that hypertension in these rats can be prevented by treatment with angiotensin-converting enzyme inhibitors. The current experiment examined the effect of losartan, an angiotensin II antagonist, on blood pressure in RRM and intact rats after a 3-fold increase in salt intake. It was found that chronic treatment with i.v. losartan (3 mg/kg/day) completely prevented sodium-induced hypertension in the RRM rats, whereas neither increased salt intake nor losartan treatment affected blood pressure in the intact rats. The antihypertensive effect of losartan was associated with an apparent renoprotective effect in RRM rats (blood urea nitrogen concentration rose in untreated animals, but remained stable in treated animals), but was not accompanied by chronic changes in water or sodium balance. The ability of losartan to prevent RRM hypertension suggests that angiotensin II is necessary for the development of this model of hypertension.
Department of Pharmacology and Toxicology, Michigan State University, East Lansing.
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Kanagy
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Fink
D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000502:physiology; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001713:Biphenyl Compounds / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006977:Hypertension, Renal / Q000139:chemically induced / Q000517:prevention & control*; D007093:Imidazoles / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects / Q000502:physiology* / Q000601:surgery; D019808:Losartan; D008297:Male; D009392:Nephrectomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012965:Sodium Chloride; D013777:Tetrazoles / Q000494:pharmacology*
D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D001713:Biphenyl Compounds; D007093:Imidazoles; D013777:Tetrazoles; D000804:Angiotensin II; D012965:Sodium Chloride; D019808:Losartan