Renal Vascular Reactivity in Mice

Abstract

Abstract. The present study describes methodology and its application to evaluate renal reactivity in acute studies on anesthetized mice. Renal blood flow (RBF) was measured using an ultrasonic transit-time flowmeter and a non-cannulating V-shaped probe. An intrarenal artery injection technique established feasibility and reproducibility of studies of renal vascular reactivity to angiotensin II (AngII) in adult wild-type mice. The study also examined whether AngII would affect RBF in mice lacking AT1Areceptors due to gene targeting. Mean arterial pressure averaged 83 and 62 mmHg, respectively, in mice with and without AT1Areceptors. The RBF was similar in both groups, averaging 7 ml/min per g kidney wt. AngII injection (10-μl bolus) into the renal artery produced transient, dose-dependent, selective reductions in RBF in AT1Aknockout mice as well as wild-type mice. The response was considerably greater in mice with AT1Areceptors: 10% for 0.1 ng, 30% for 1 ng, and 45% for 5 ng AngII in control animalsversusrespective decreases of 6, 15, and 17% in knockout mice. In other studies, angiotensin-converting enzyme (captopril) or renin (CP-71362-14) was inhibited. During inhibition of AngII formation, renal vascular reactivity to AngII increased twofold in both groups. Coadministration of the AT1receptor antagonist losartan (1 to 1000 ng) elicited dose-dependent inhibition of AngII effects, with near maximum blockage of 80 to 90% in both groups of mice. The putative AT2receptor antagonist PD 123319 inhibited 30 to 40% of AngII-induced vasoconstriction, whereas CGP 42112 had no effect in either group. In conclusion, AngII can elicit renal vasoconstriction, albeit attenuated, in AT1Aknockout mice. The weaker RBF effects are most likely due to the absence of the AT1Areceptor. Inhibition of the response by AT1receptor antagonist suggests mediation by the AT1Breceptor in these animals. The residual constrictor effect observed during AT1receptor blockade and sensitive to PD 123319 appears to be mediated by a non-AT1receptor.