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Effects of bradykinin B 2 receptor antagonism on the hypotensive effects of ACE inhibition
Author(s) -
Bouaziz Herve,
Joulin Yves,
Safar Michel,
Benetos Athanase
Publication year - 1994
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 - 10.1111/j.1476-5381.1994.tb17052.x
Subject(s) - bradykinin , endocrinology , medicine , nicardipine , angiotensin converting enzyme , icatibant , antagonist , angiotensin ii , bradykinin receptor , pharmacology , chemistry , receptor , blood pressure
1 The aim of this study was to determine the participation of endogenous bradykinin (BK) in the antihypertensive effects of the angiotensin converting enzyme inhibitor (ACEI), perindoprilat, in the spontaneously hypertensive rat (SHR) on different salt diets. 2 Conscious SHRs receiving either a low or a high NaCl diet were used in order to evaluate the respective roles of angiotensin II suppression and bradykinin stimulation in the acute hypotensive effects of perindoprilat. Two different B 2 receptor antagonists (B 4146 and Hoe 140) were used after bolus administration of 7 mg kg −1 of the ACEI, perindoprilat. In separate animals, Hoe 140 was administered before the injection of perindoprilat. In other experiments, the effects of Hoe 140 on the hypotensive effects of the calcium antagonist, nicardipine, were tested. 3 The different NaCl diets had no effect on baseline blood pressure. Hoe 140 injection before ACE inhibition did not modify blood pressure. Perindoprilat caused more marked hypotension in the low salt‐fed rats than in the high salt animals ( P < 0.01). Administration of Hoe 140 or B4146 after perindoprilat significantly reduced the antihypertensive effects of perindoprilat in the different groups, but this effect was more pronounced in high salt‐fed rats. However, in SHRs receiving Hoe 140 before perindoprilat, the antihypertensive effect of perindoprilat was completely abolished in both high or low salt diet rats. In separate experiments we confirmed that Hoe 140 did not affect the hypotensive efficacy of the calcium antagonist, nicardipine. 4 Our study shows that inhibition of endogenous bradykinin degradation participates in the acute antihypertensive effects of perindoprilat in SHRs. The role of bradykinin is more pronounced following exposure to a high salt diet i.e., when the renin‐angiotensin system is suppressed. Blockade of bradykinin B 2 receptors by Hoe 140 before administration of perindoprilat completely abolished the hypotensive effect of perindoprilat suggesting an increased role of bradykinin in the onset of hypotensive action of ACE inhibitors. However, the exact mechanism of this interaction remains unclear.