Published online before print October 16, 2003, doi: 10.1161/01.RES.0000101912.01071.FF
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Submitted on August 12, 2003
Revised on September 26, 2003
Accepted on October 6, 2003
AT1b Receptor Predominantly Mediates Contractions in Major Mouse Blood Vessels
Yingbi Zhou ;
From the Department of Physiology and Cell Biology (Y.Z., W.P.D., M.P.), College of Medicine and Public Health, The Ohio State University, Columbus, Ohio; Department of Pharmacology and Toxicology (Y.C., M.M.), Wright State University School of Medicine, Dayton, Ohio.
* To whom correspondence should be addressed. E-mail: periasamy.1{at}osu.edu.
In rodents, angiotensin (Ang) II type-1 (AT1) receptors exist as two pharmacologically identical subtypes: AT1a and AT1b. Recent studies have utilized mouse models with specific subtype receptor deletions to differentiate the functional difference between AT1 subtypes. However, little information is available on AT1 subtype expression in mouse vasculature. Therefore, in this study, AT1a-/- mice and wild-type littermates (AT1a+/+) were used to examine AT1 subtype expression and its functional relevance in mouse arterial vessels. Using RT-PCR and restriction enzyme digestion, we showed that AT1b accounts for most of the total AT1 mRNA in mouse abdominal aorta and femoral artery. In contrast, AT1a is the predominant subtype in kidney. To study the functional role of AT1 subtypes, we measured the in vitro contractility in vessels from AT1a-/- and AT1a+/+ mice. The Ang II concentration response curves in abdominal aorta and femoral artery were comparable between the two mouse strains. Furthermore, the Ang II response in AT1a-/- mouse vessels was completely antagonized by losartan, an AT1 antagonist. These results demonstrate that AT1b receptor is a major mediator for Ang II contractile response in mouse vessels, such as abdominal aorta and femoral artery.
Key words: angiotensin II • AT1 • subtype • vasoconstriction
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