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 (AT(1)) receptor: AT(1A) and AT(1B). It is unclear which receptor subtype mediates contraction in response to angiotensin II in various arteries. We tested the hypothesis that the AT(1B) 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 AT(1B) 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 AT(1B) receptor knockout mice. Contractions in response to K(+) and U46619 (thromboxane A(2) mimetic) were not different between rings obtained from wild-type and AT(1B) 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 AT(1B) receptor. Our data support the concept that AT(1B) receptors couple to contraction in the mouse abdominal aorta, a function that parallels the single known AT(1) receptor in human vascular smooth muscle.
Swafford
Albert N
AN
Physiology, Louisiana State University Health Sciences Center, New Orleans, Louisiana.
Harrison-Bernard
Lisa M
LM
Dick
Gregory M
GM
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D001012:Aorta, Abdominal / Q000378:metabolism; D066298:In Vitro Techniques; D007537:Isometric Contraction; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D009213:Myography; D011189:Potassium Chloride / Q000494:pharmacology; D044140:Receptor, Angiotensin, Type 1 / Q000172:deficiency* / Q000235:genetics; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D044140:Receptor, Angiotensin, Type 1; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D011189:Potassium Chloride; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid