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Effect of chronic bradykinin B 2 receptor blockade on blood pressure of conscious Dahl salt‐resistant rats
Author(s) -
Mukai Hiroya,
Fitzgibbon Wayne R,
Ploth David W,
Margolius Harry S
Publication year - 1998
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0701797
Subject(s) - bradykinin , endocrinology , medicine , antagonist , blood pressure , chemistry , receptor , receptor antagonist
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 B 2 receptor antagonist, Hoe 140 ( D ‐Arg[Hyp 3 , Thi 5 , D ‐Tic 7 , Oic 8 ]‐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 B 2 receptors 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.