Chronic Bradykinin Infusion and Receptor Blockade in Angiotensin II Hypertension in Rats

Abstract

Abstract —The influence of endogenous bradykinin(BK) on the control of arterial pressure and the development of cardiac hypertrophy was assessed in chronically angiotensin II(Ang II)–infused rats (200 ng · kg −1 · min −1 ) through the effects of concomitant infusion of 3 doses of BK (15 ng · kg −1 · d −1 , 100 ng · kg −1 · d −1 and 100 ng · kg −1 · min −1 ie, 144 000 ng · kg −1 · d −1 ) or BK-blockade by Hoe140 (300 μg · kg −1 · d −1 ) for 10 days. In Ang II–infused rats, tail-cuff pressure increased from 124±3 to 174±6 mm Hg ( P <0.001). The pressor effect of Ang II was not affected by simultaneous infusion of BK or Hoe140. At the end of the experiments, cardiac mass was higher in rats infused with Ang II alone (3.56±0.10 versus 2.89±0.05 mg/g in untreated controls, P <0.01) and the development of cardiac hypertrophy was not modified by administration of the 3 doses of BK or Hoe140. In addition, the fall in cardiac output associated with Ang II was prevented only by the moderate and high doses of BK, mainly through an increase in stroke volume and a decrease in total peripheral resistance. In the same way, the renal vasoconstrictor effect of Ang II was abolished by the medium and high dose of BK. Hoe140 did not affect cardiac output or renal blood flow in this model. No influence of BK or Hoe140 on the increase in albuminuria induced by Ang II was detected. In conclusion, exogenous BK may oppose the effect of Ang II on vascular tone, but it cannot prevent hypertension and target-organ damage associated with this experimental model of hypertension, even at a very high dose.