Knockout Mice Reveal That the Angiotensin II type 1B Receptor Links to Smooth Muscle Contraction

Background Rodents express two isoforms of the angiotensin II type 1 (AT1) receptor: AT1A and AT1B. It is unclear which receptor subtype mediates contraction in response to angiotensin II in various arteries. We tested the hypothesis that the AT1B receptor is the predominant receptor that mediates contraction in the abdominal aorta in response to angiotensin II. Methods Isometric tension responses to angiotensin II were determined in abdominal aortic rings obtained from male wild-type and AT1B receptor knockout mice. The rings were suspended in an organ bath of a wire myograph and contractions to angiotensin II and other vasoconstrictors were determined. Results Angiotensin II contracted aortic segments from wild-type mice; however, this response was virtually absent in rings obtained from AT1B receptor knockout mice. Contractions in response to K+ and U46619 (thromboxane A2 mimetic) were not different between rings obtained from wild-type and AT1B receptor knockout mice. Conclusions Reduced angiotensin II contraction is not related to a generalized decrease in smooth muscle function, rather it is specifically due to genetic ablation of the AT1B receptor. Our data support the concept that AT1B receptors couple to contraction in the mouse abdominal aorta, a function that parallels the single known AT1 receptor in human vascular smooth muscle.