Chiu N, Reid I A
Department of Physiology, University of California, San Francisco 94143-0444, USA.
J Hypertens. 1997 May;15(5):517-21. doi: 10.1097/00004872-199715050-00007.
There is evidence that kinins contribute to some of the renal, cardiovascular, and endocrine effects of the diuretic furosemide. The aim of the present study was to investigate the role of kinins in the regulation of renin secretion, blood pressure, and heart rate under resting conditions and after administration of furosemide.
The effects of icatibant, a potent, specific, and long-lasting bradykinin B2 receptor antagonist, on resting renin secretion, blood pressure, and heart rate, and on the responses of these variables to administration of furosemide, were investigated in conscious, chronically prepared rabbits.
Injection of icatibant in doses of 0.1 and 1.0 mg/kg blocked the hypotensive response to intravenous injections of bradykinin completely. The lower dose of icatibant decreased plasma renin activity in some animals, but did not alter their blood pressure or heart rate. The higher dose suppressed resting plasma renin activity from 10.2 +/- 2.2 to 5.6 +/- 1.4 ng/ml/2 h (P < 0.01), without changing the blood pressure or heart rate. Injection of furosemide (2 mg/kg) caused a sustained increase i plasma renin activity from 6.7 +/- 1.6 to 15.9 +/- 3.3 ng/ml/2h (P < 0.01), a transient increase in mean arterial pressure from 72 +/- 3 to 78 +/- 3 mmHg (P < 0.05), and a sustained increase in heart rate from 228 +/- 8 to 253 +/- 6 bpm (P < 0.01). Neither dose of icatibant altered the cardiovascular and renin responses to furosemide.
These results provide evidence that bradykinin B2 receptors participate in the regulation of resting renin secretion, but not in the renin secretory or heart rate responses to furosemide.
有证据表明激肽参与了利尿药呋塞米的一些肾脏、心血管及内分泌效应。本研究的目的是探讨激肽在静息状态下以及给予呋塞米后对肾素分泌、血压和心率调节中的作用。
在清醒、长期制备的家兔中，研究了强效、特异且长效的缓激肽B2受体拮抗剂依替巴肽对静息肾素分泌、血压和心率，以及这些变量对给予呋塞米反应的影响。
静脉注射剂量为0.1和1.0mg/kg的依替巴肽可完全阻断静脉注射缓激肽引起的降压反应。较低剂量的依替巴肽可使部分动物的血浆肾素活性降低，但未改变其血压或心率。较高剂量可将静息血浆肾素活性从10.2±2.2降至5.6±1.4ng/ml/2h（P<0.01），而血压和心率未改变。注射呋塞米（2mg/kg）可使血浆肾素活性从6.7±1.6持续升高至15.9±3.3ng/ml/2h（P<0.01），平均动脉压从72±3短暂升高至78±3mmHg（P<0.05），心率从228±8持续升高至253±6次/分钟（P<0.01）。两种剂量的依替巴肽均未改变对呋塞米的心血管及肾素反应。
这些结果表明缓激肽B2受体参与静息肾素分泌的调节，但不参与对呋塞米的肾素分泌或心率反应。
