EFFECT OF TERTATOLOL AND OF ITS METABOLITES AND STRUCTURAL ANALOGS IN ISOLATED PERFUSED RAT-KIDNEY VASCULATURE

被引:4
作者
STEPHAN, D
BARTHELMEBS, M
KRIEGER, JP
DECKER, N
ROCHAT, C
IMBS, JL
机构
[1] CTR HOSP REG UNIV STRASBOURG, SERV HYPERTENS & MALAD, STRASBOURG, FRANCE
[2] INST RECH INT SERV, NEUILLY SUR SEINE, FRANCE
关键词
Isolated rat kidney; Renal vasculature; Serotonin; Tertatolol; β-blockers;
D O I
10.1097/00005344-199008000-00022
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The renal vascular effect of tertatolol and analogues was investigated in isolated rat kidney perfused at constant flow in an open circuit with Krebs-Henseleit solution after vascular tone had been reestablished by bolus injections of serotonin or other vasoconstrictor drugs. Against serotonin-induced vasoconstriction, (±)tertatolol (3 x 10-7-3 x 10-5 M) evoked concentration-dependent relaxation (IC50 = 4.6 ± 0.4 x 10-6 M), (−) tertatolol was more active than the racemic and (+)tertatolol was less active. (±)Tertatolol competitively antagonized serotonin-induced renal constriction (pA2 = 5.6 ± 0.2). Tertatolol metabolites (4-OH tertatolol, 4,5-di-OH tertatolol, and sulfoxy tertatolol) were inactive. (±)Sotalol and (±)nadolol, were also inactive in this model and (−) bunolol induced renal vasodilatation only at concentrations 40 times higher than (−) tertatolol. The renal response to tertatolol was not linked to release of prostaglandins or dopamine or to interaction with the dopamine receptor, since neither indomethacin nor SCH 23390 affected tertatolol-induced renal vasodilatation. Tertatolol also elicted relaxation of N6-cyclohexyladenosine-induced renal vasoconstriction (34 ± 7% relaxation at 3 x 10-5 M) but was inactive when renal vascular tone was raised by prostaglandin F2α, angiotensin II, or neuropeptide Y in the presence of norepinephrine. © 1990 Raven Press, Ltd., New York.
引用
收藏
页码:338 / 346
页数:9
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