Renal vascular reactivity in mice: AngII-induced vasoconstriction in AT1A receptor null mice.

Journal Article (Journal Article)

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 AT1A receptors due to gene targeting. Mean arterial pressure averaged 83 and 62 mmHg, respectively, in mice with and without AT1A receptors. The RBF was similar in both groups, averaging 7 ml/min per g kidney wt. AngII injection (10-microl bolus) into the renal artery produced transient, dose-dependent, selective reductions in RBF in AT1A knockout mice as well as wild-type mice. The response was considerably greater in mice with AT1A receptors: 10% for 0.1 ng, 30% for 1 ng, and 45% for 5 ng AngII in control animals versus respective 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 AT1 receptor 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 AT2 receptor 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 AT1A knockout mice. The weaker RBF effects are most likely due to the absence of the AT1A receptor. Inhibition of the response by AT1 receptor antagonist suggests mediation by the AT1B receptor in these animals. The residual constrictor effect observed during AT1 receptor blockade and sensitive to PD 123319 appears to be mediated by a non-AT1 receptor.

Full Text

Duke Authors

Cited Authors

  • Ruan, X; Oliverio, MI; Coffman, TM; Arendshorst, WJ

Published Date

  • December 1999

Published In

Volume / Issue

  • 10 / 12

Start / End Page

  • 2620 - 2630

PubMed ID

  • 10589703

International Standard Serial Number (ISSN)

  • 1046-6673

Digital Object Identifier (DOI)

  • 10.1681/ASN.V10122620


  • eng

Conference Location

  • United States