Role of endothelin receptors in the hypertensive state of kinin B2 knockout mice subjected to a high-salt diet

被引:15
作者
Brochu, I
Labonté, J
Bkaily, G
D'Orleans-Juste, P [1 ]
机构
[1] Univ Sherbrooke, Fac Med, Dept Pharmacol, Inst Pharmacol, Sherbrooke, PQ J1H 5N4, Canada
[2] Univ Sherbrooke, Fac Med, Dept Anat & Cellular Biol, Sherbrooke, PQ J1H 5N4, Canada
关键词
angiotensin II; antagonist; reverse transcriptase-PCR; plethysmography; preproendothelin-1;
D O I
10.1042/CS103S380S
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Mice with disruption of the kinin B-2 receptor (B2KO mice) are sensitive to salt-rich diets, which causes hypertension. The aim of the study was to assess the role of endothelin-1 (ET-1) and angiotensin-II in hypertensive B2KO mice on a salt-rich diet. We also wanted to verify if there is an upregulation of the mRNA expression of the precursors or receptors for these hormones. Two groups of B2KO mice (20-25 g) were investigated. The first group received an 8% NaCl diet with 1% NaCl in drinking water (HS) and the second was fed with normal food with tap water (NS). The antagonists tested were the ETA receptor antagonist BQ-123 (1 and 5 mg/kg), the ETB receptor antagonist BQ-788 (0.25 and 1 mg/kg), the angiotensin receptor type 1 antagonist losartan (10 mg/kg) and the angiotensin-converting enzyme inhibitor captopril (3 mg/kg). These were injected intraperitoneally 30 min prior to blood pressure measurement by the tail-cuff method. We also studied the level of expression of preproET-1, ET-1 receptors, angiotensinogen and angiotensin receptors by RNA extraction from the heart and kidneys of these mice followed by reverse transcriptase (RT)-PCR. B2KO mice (HS) were hypertensive after 8 weeks compared with B2KO mice on normal diet (HS, 93.4+/- 1.5 mmHg, n = 7; NS, 61.4+/-2.7 mmHg, n = 7). In the HS group, the mean arterial blood pressure was significantly reduced by BQ-123 (5 mg/kg) to 61.9+/- 1.8 mmHg (n = 7), by BQ-788 (1 mg/kg) to 58.8+/-2.6 mmHg (n = 6), by losartan (10 mg/kg) to 73.2 +/- 1.7 mmHg (n = 8) and by captopril (3 mg/kg) to 86.0 +/- 2.3 mmHg (n = 8). The expression studied by RT-PCR did not show any difference (either in precursors or receptors expression) between hypertensive and normal mice. The four antagonists used seemed to reverse the hypertension. These results suggest that ET-1 and angiotensin-II are probably involved in the mechanism that leads to hypertension since the effect of these hormones is probably not compensated by kinins in B2KO mice. Further studies are necessary to understand the implication of the cross-talk between these hormones in the hypertensive state.
引用
收藏
页码:380S / 384S
页数:5
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