曲洛司坦对氢氯噻嗪治疗的大鼠和犬的保钾作用。

Potassium-sparing effect of trilostane in hydrochlorothiazide-treated rats and dogs.

作者信息

DeFelice A F, Brousseau A C, O'Connor B

出版信息

Proc Soc Exp Biol Med. 1987 Jan;184(1):1-6. doi: 10.3181/00379727-184-42437.

Abstract

Trilostane, which inhibits three beta-hydroxysteroid dehydrogenase and aldosterone synthesis in rats and monkeys, significantly attenuated the oral potassium-wasting effect of hydrochlorothiazide (HCTZ) in rats and dogs when coadministered with the diuretic. The steroid reduced the kaliuretic and enhanced the natriuretic (and hyperreninemic) activity of HCTZ in rats, thereby promoting the urinary sodium/potassium ratio. Trilostane completely prevented HCTZ-induced hypokalemia in dogs and tended to reduce the degree of secondary aldosteronism. The combination also promoted hematocrit of dogs by 8% and decreased serum Na+ concentration by 7 meq/liter. When administered alone, trilostane increased canine serum potassium levels slightly and promoted rat urinary Na+/K+ ratio. Results confirm previous reports of antikaliuretic activity of trilostane in diuretic-treated rats. Further, the data indicate that frank hypokalemia induced in dogs by hydrochlorothiazide can be prevented by adjunctive trilostane therapy without eliciting hyperkalemia.

摘要

曲洛司坦可抑制大鼠和猴体内的3β-羟基类固醇脱氢酶及醛固酮合成，与利尿剂氢氯噻嗪（HCTZ）合用时，能显著减弱其在大鼠和犬体内导致口服钾流失的作用。该类固醇降低了HCTZ在大鼠体内的促尿钾排泄作用，并增强了其利钠（及高肾素血症）活性，从而提高了尿钠/钾比值。曲洛司坦完全预防了犬因HCTZ诱导的低钾血症，并倾向于降低继发性醛固酮增多症的程度。该联合用药还使犬的血细胞比容提高了8%，血清钠浓度降低了7毫当量/升。单独给药时，曲洛司坦可使犬血清钾水平略有升高，并提高大鼠尿钠/钾比值。结果证实了之前关于曲洛司坦在接受利尿剂治疗的大鼠中具有抗尿钾排泄活性的报道。此外，数据表明，氢氯噻嗪诱导犬出现的明显低钾血症可通过联用曲洛司坦治疗加以预防，且不会引发高钾血症。