EFFECT OF CHRONIC BRADYKININ B-2 RECEPTOR BLOCKADE ON BLOOD-PRESSURE OF CONSCIOUS DAHL SALT-RESISTANT RATS

1 In this study 3 protocols were utilized to determine the role of end ogenous kinins in the resistance of the inbred Dahl (Rapp) salt-resist ant (SR/Jr) rats to high salt diet-induced blood pressure elevation. 2 The bradykinin B-2 receptor antagonist, Hoe 140 (D-Arg[Hyp(3), Thi(5) , D-Tic(5), 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 attenuat ed the hypotensive responses to 100-1000 ng of bradykinin. 3 In the fi rst protocol, 5 week old SR/Jr rats treated with Hoe 140 (10-20 nmol d ay(-1), n = 9, s.c., via osmotic minipumps) for 3 weeks and concomitan tly fed high (8%) NaCl diet had significantly higher conscious tail cu ff blood pressures (BPc) at 1 and 3 weeks when compared with rats trea ted with vehicle (0.9% NaCl, n = 6). The differences in BPc between th e 2 groups were 13 mmHg (P < 0.001) after 1 week and 8 mmHg (P < 0.05) after 3 weeks of treatment. 4 In the second protocol, 5 week old SR/J r 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 w eek of treatment the rats were fed normal (0.8%) NaCl diet. The rats w ere then switched to 8% NaCl for 2 remaining weeks of the protocol. Th e mean BPc of Hoe 140-treated rats was not significantly different fro m that of the vehicle-treated rats when fed 0.8% NaCl diet. In contras t, rats treated with Hoe 140 and concomitantly fed high (8%) NaCl diet had significantly increased BPc (123 +/- 2 vs 111 +/- 1 mmHg, P < 0.0 01 for the Hoe 140- and vehicle-treated rats, respectively). 5 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. 6 At the end of 3 weeks of study, blood pressure was measured via an arterial cathe ter during pentobarbitone-induced anaesthesia. Rats treated with Hoe 1 40 for 1 or 3 weeks had significantly lower mean arterial blood pressu res than the vehicle-treated rats. 7 Our findings suggest that in SR/J r rats, kinin activation of bradykinin B 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 u nderlying the decreased blood pressure during pentobarbitone anaesthes ia of SR/Jr rats chronically treated with Hoe 140 has yet to be elucid ated.