Effect of chronic bradykinin B2 receptor blockade on blood pressure of conscious Dahl salt-resistant rats.
Effect of chronic bradykinin B2 receptor blockade on blood pressure of conscious Dahl salt-resistant rats.
复制标题
慢性缓激肽 B2 受体阻断对清醒 Dahl 耐盐大鼠血压的影响。
DOI：
10.1038/sj.bjp.0701797
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发表时间：
1998
期刊：
影响因子：
--
通讯作者：
Margolius,HS
中科院分区：
文献类型：
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作者：
Mukai,H;Fitzgibbon,WR;Ploth,DW;Margolius,HS
在这项研究中，利用3种方案来确定内源性激肽在近交系Dahl（Rapp）耐盐（SR/Jr）大鼠对高盐饮食诱导的血压升高的抵抗中的作用。（D-Arg [Hyp 3，Thi 5，D-Tic 7，Oic 8]-缓激肽），剂量为10-20或20-40 nmol/天（皮下（s.c.），通过渗透微泵，在高（8%）盐饮食期间持续1或3周）有效地阻断或减弱了对100-1000 ng缓激肽的肿胀反应。用Hoe 140（10-20 nmol，第-1天，n=9，s.c.，通过渗透微型泵）给药3周并同时喂食高（8%）NaCl饮食的大鼠在第1周和第3周时与用载体（0.9%NaCl，n=6）处理的大鼠相比具有显著更高的清醒尾袖血压（BPc）。治疗1周后，两组之间的BPc差异为13 mmHg（P<0.001），治疗3周后为8 mmHg（P<0.05）。在第二个方案中，5周龄SR/Jr大鼠接受Hoe 140（20-40 nmol/天，n=8，s.c.，通过渗透微型泵）或赋形剂（n=8）持续3周。在给药的第一周，大鼠喂食正常（0.8%）NaCl饲料。然后在方案的剩余2周内将大鼠转换为8% NaCl。当喂食0.8% NaCl饲料时，Hoe 140给药大鼠的平均BPc与溶媒给药大鼠的平均BPc无显著差异。相比之下，用Hoe 140处理并同时喂食高（8%）NaCl饲料的大鼠BPc显著增加（Hoe 140和溶剂处理大鼠分别为123±2 vs 111±1 mmHg，P<0.001）。通过渗透压微型泵）在高盐饮食期间没有增加预先暴露于高盐饮食2周的大鼠的BPc。在3周的研究结束时，在戊巴比妥诱导的麻醉期间通过动脉导管测量血压。Hoe 140处理1周或3周的大鼠平均动脉血压显著低于溶剂处理的大鼠。我们的研究结果表明，在SR/Jr大鼠中，缓激肽B2受体的激肽激活至少部分有助于抵抗暴露于高盐饮食后血压升高的早期调节机制。在戊巴比妥麻醉SR/Jr大鼠期间，Hoe 140长期给药导致血压降低的机制尚未阐明。
In this study 3 protocols were utilized to determine the role of endogenous kinins in the resistance of the inbred Dahl (Rapp) salt‐resistant (SR/Jr) rats to high salt diet‐induced blood pressure elevation.The bradykinin B2receptor antagonist, Hoe 140 (D‐Arg[Hyp3, Thi5,D‐Tic7, Oic8]‐bradykinin) at doses of either 10–20 or 20–40 nmol day−1(subcutaneously (s.c), via osmotic minipumps, for either 1 or 3 weeks during a high (8%) salt diet) effectively blocked or attenuated the hypotensive responses to 100–1000 ng of bradykinin.In the first protocol, 5 week old SR/Jr rats treated with Hoe 140 (10–20 nmol day−1,n=9, s.c., via osmotic minipumps) for 3 weeks and concomitantly fed high (8%) NaCl diet had significantly higher conscious tail cuff blood pressures (BPc) at 1 and 3 weeks when compared with rats treated with vehicle (0.9% NaCl,n=6). The differences in BPc between the 2 groups were 13 mmHg (P<0.001) after 1 week and 8 mmHg (P<0.05) after 3 weeks of treatment.In the second protocol, 5 week old SR/Jr rats were treated with Hoe 140 (20–40 nmol day−1,n=8, s.c., via osmotic minipumps) or vehicle (n=8) for 3 weeks. During the first week of treatment the rats were fed normal (0.8%) NaCl diet. The rats were then switched to 8% NaCl for 2 remaining weeks of the protocol. The mean BPc of Hoe 140‐treated rats was not significantly different from that of the vehicle‐treated rats when fed 0.8% NaCl diet. In contrast, rats treated with Hoe 140 and concomitantly fed high (8%) NaCl diet had significantly increased BPc (123±2 vs 111±1 mmHg,P<0.001 for the Hoe 140‐ and vehicle‐treated rats, respectively).In the third protocol, treatment with Hoe 140 (20–40 nmol day−1, s.c., via osmotic minipumps) during high salt diet did not increase BPc in rats that were pre‐exposed to the high salt diet for 2 weeks.At the end of 3 weeks of study, blood pressure was measured via an arterial catheter during pentobarbitone‐induced anaesthesia. Rats treated with Hoe 140 for 1 or 3 weeks had significantly lower mean arterial blood pressures than the vehicle‐treated rats.Our findings suggest that in SR/Jr rats, kinin activation of bradykinin B2receptors at least partially contributes to early regulatory mechanisms that resist an increase in blood pressure following exposure to a high salt diet. The mechanism underlying the decreased blood pressure during pentobarbitone anaesthesia of SR/Jr rats chronically treated with Hoe 140 has yet to be elucidated.