Characterization of angiotensin-(1-7) receptor subtype in mesenteric arteries.
Mesenteric arteries from male Sprague-Dawley rats were mounted in a pressurized myograph system. Ang-(1-7) concentration-dependent responses were determined in arteries preconstricted with endothelin-1 (10(-7)M). The receptor(s) mediating the Ang-(1-7) evoked dilation were investigated by pretreating the mesenteric arteries with specific antagonists of Ang-(1-7), AT(1) or AT(2) receptors. The effects of Ang-(3-8) and Ang-(3-7) were also determined. Ang-(1-7) caused a concentration-dependent dilation (EC(50): 0.95 nM) that was blocked by the selective Ang-(1-7) receptor antagonist D-[Ala(7)]-Ang-(1-7). Administration of a specific antagonist to the AT(2) receptor (PD123319) had no effect. On the other hand, losartan and CV-11974 attenuated the Ang-(1-7) effect. These results demonstrate that Ang-(1-7) elicits potent dilation of mesenteric resistance vessels mediated by a D-[Ala(7)]-Ang-(1-7) sensitive site that is also sensitive to losartan and CV-11974.
The Hypertension and Vascular Disease Center, Wake Forest University School of Medicine, Winston-Salem, NC 27157-1932, USA.
Liomar A A
LA
Neves
David B
DB
Averill
Carlos M
CM
Ferrario
Mark C
MC
Chappell
Judy L
JL
Aschner
Michael P
MP
Walkup
K Bridget
KB
Brosnihan
D000803:Angiotensin I / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D019332:Endothelin-1 / Q000494:pharmacology; D008297:Male; D008638:Mesenteric Arteries / Q000378:metabolism*; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011945:Receptors, Angiotensin / Q000145:classification* / Q000378:metabolism*; D014664:Vasodilation / Q000187:drug effects
D000959:Antihypertensive Agents; D019332:Endothelin-1; D010446:Peptide Fragments; D011945:Receptors, Angiotensin; D000803:Angiotensin I; C118790:angiotensin I (1-7)