1008 ANGIOTENSIN TYPE-2 RECEPTOR CONTRIBUTES TO REDUCED VASCULAR RESPONSE TO ANGIOTENSIN-II IN YOUNG RATS

Abstract

Background: The angiotensin type-2 receptor (AT2R) is known to oppose the vasoconstrictive actions of angiotensin II (AngII). During fetal development AT2R expression is very high, which upon maturation regresses. The present study investigates the sensitivity to acute AngII in young rats and the contribution of the AT2R in attenuating the vasoconstrictor response to AngII. Methods: Male Sprague-Dawley rats at 3 and 6 weeks of age were anesthetized. Mean arterial pressure (MAP) and renal blood flow (RBF; transonic flowmeter), was measured in response to i.v. administration of AngII at 0 (basal) 10 (10AngII) and 100ng/kg/hr (100AngII). The AT2R inhibitor, PD-123319, was given and responses to 100AngII were repeated. Results: In the 6wk rats, 10 and 100AngII increased MAP (89 ± 4 mmHg) by 10 ± 7 and 18 ± 5 mmHg, respectively. Likewise, RBF (4.0 ± 0.6 ml/min/gkw) was reduced by 8 ± 3% and 34 ± 3%. In the 3wk rats basal MAP and RBF were 72 ± 4 mmHg and 2.9 ± 0.3 ml/min/gkwt, The 10AngII dose had no effect on MAP, while 100AngII increased MAP by 6 ± 2 mmHg. RBF in the 3wk rats was not was not affected by the 10ng AngII dose (-2 ± 1% change), while the higher dose produced a 10 ± 3% decrease. PD-123319 potentiated the change in RBF to 100AngII in the 3wk animals (23 ± 4% reduction), but had no additional effect in the 6wk rats. Conclusions: These data indicate that during development, the presence of the AT2R in young rodents contributes to the attenuated vasoconstrictor response to AngII. These findings may have implication for the use of drugs that inhibit the renin-angiotensin system for the treatment of pediatric hypertension and renal failure.