Role of metabolism and receptor responsiveness in the attenuated responses to Angiotensin II in mice compared to rats

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30 Scopus citations


Chronic infusion of Angiotensin II (AngII) to rats is a well-characterized model for determining AngII physiology. Genetic manipulations have strengthened knowledge of AngII; however, they do not permit an increase in AngII to be initiated at a selected age, duration and dose. Therefore, exogenous AngII administration remains an important technique to define its biological effect. We previously noted that infusion of AngII to mice had minimal effects compared to the same dose given to rats. In this study, we compared the effects of chronic infusion of the same dose of AngII to C57BL/6 mice and Sprague-Dawley rats, two commonly used rodent models. Rats administered AngII exhibited reductions (by 22%) in body weight, which were not evident in mice. AngII increased blood pressure by 54 mm Hg in rats, but had no effect in mice. Vascular histology demonstrated that AngII caused medial hypertrophy in rats, with adventitial expansion in mice. Plasma concentrations of AngII and its catabolic fragments were elevated (twofold) in mice compared to rats. Angiotensin receptor affinity, density and distribution were similar in rats and mice. Infusion of AngII decreased AngII receptor density in the kidney (by 78%) and spleen (by 29%) of mice, but had no effect in rats. AngII produced a sustained contractile response in rat aortic strips, but minimal responses in mouse aorta. These results demonstrate that differences in circulating angiotensin peptides, AngII receptor regulation, and vascular reactivity contribute to diminished responses to AngII infusion in mice compared to rats. Results from this study suggest that considerably higher doses of AngII may be required to elicit physiologic effects of AngII in mice.

Original languageEnglish
Pages (from-to)107-116
Number of pages10
JournalRegulatory Peptides
Issue number2
StatePublished - Feb 15 2004

Bibliographical note

Funding Information:
The authors thank the skilled technical assistance of Marc Helton in the studies on chronic AngII infusion to rats. These studies were supported by NIH HL62846 (AD, LC), NIH HL64121 (LC) and HL67284 (MCG).


  • Angiotensin
  • Blood pressure
  • Differences between rats and mice

ASJC Scopus subject areas

  • Endocrinology
  • Cellular and Molecular Neuroscience
  • Biochemistry
  • Physiology
  • Clinical Biochemistry


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