LACK OF INVOLVEMENT OF BRADYKININ IN THE VASCULAR SYMPATHOINHIBITORY EFFECTS OF ANGIOTENSIN-CONVERTING ENZYME-INHIBITORS IN SPONTANEOUSLY HYPERTENSIVE RATS

1 The aim of this study was to investigate the contribution of endogenous bradykinin to the vascular sympathoinhibitory effects exerted by angiotensin I converting enzyme inhibitors (ACEIs) in the spontaneously hypertensive rat (SHR). 2 Adult SHRs were treated daily for 8 days with either perindopril (3 mg kg(-1)), or a selective angiotensin II AT(1) receptor antagonist, losartan (10 mg kg(-1)) both given orally - these two doses being equipotent in inhibiting angiotensin I (AI)-induced vascular responses-or distilled water (controls). After pithing, the animals were instrumented for determination of blood pressure, heart rate, cardiac output, regional (renal, mesenteric, hindlimb) blood flows (pulsed Doppler technique) and corresponding vascular resistances. Afterwards, half of the animals of each group were given the selective bradykinin B-2 receptor antagonist, icatibant, used in a dose (10 mu g kg(-1), i.v.) that achieved Bz receptor blockade, the other half received saline (10 mu l kg(-1), i.v.). Haemodynamic responses to increasing frequencies of spinal cord stimulation were then measured. 3 Presser and vasoconstrictor responses to AI were significantly and similarly reduced in both perindopril- and losartan-treated groups. Perindopril and losartan both decreased to a similar extent the presser and vasoconstrictor responses to electrical stimulation of the spinal cord. 4 In the dose used, icatibant did not affect any of the investigated haemodynamic parameters in any of the experimental groups. Furthermore, icatibant did not affect the stimulation frequency-response curves in the control animals and did not modify the vascular sympathoinhibitory effects exerted by perindopril and by losartan. 5 Taken together, these results demonstrate that endogenous bradykinin does not, through B-2 receptor activation, contribute to the vascular sympathoinhibitory effects of ACEIs in SHRs.