Angiotensin-(1-7) and the rat aorta: modulation by the endothelium.
Peptide metabolites of angiotensin I and II are active components of the renin-angiotensin system. One such peptide is angiotensin-(1-7), which has been shown to be present in various tissues and has properties distinct from those of angiotensin II. We examined the effects of angiotensin-(1-7) on endothelium-intact and denuded rat aorta. Second, we evaluated whether an interaction occurred between angiotensin-(1-7) and angiotensin peptides, as well as noradrenaline. Finally, we addressed whether the responses to angiotensin-(1-7) were mediated by an AT1 receptor. Angiotensin-(1-7) produced concentration-dependent relaxations of the rat aorta that were significantly greater in endothelium-intact preparations (81.1 +/- 18.9% and 29.6 +/- 2.9% for intact and denuded, respectively). Angiotensin-(1-7) inhibited responses generated to angiotensin I, II, III, and noradrenaline. In endothelium-denuded preparations, angiotensin-(1-7) produced a rightward shift of the concentration-effect curves to angiotensin II and noradrenaline. In addition, the inhibition against angiotensin I and II was significantly greater in endothelium-intact preparations [mean median inhibitory concentration (IC50) values for endothelium-intact preparations, 1.25 x 10(-9) M and 1.57 x 10(-9) M for angiotensin I and II, respectively; and for endothelium-denuded preparations, 1.77 x 10(-8) M and 1.17 x 10(-8) M for angiotensin I and II, respectively). Losartan did not affect relaxations in endothelium-intact preparations but caused a significant potentiation of the relaxation by angiotensin-(1-7) in denuded preparations. We conclude that angiotensin-(1-7) is a component of the renin-angiotensin system that acts to modulate the pressor effects of angiotensin II and noradrenaline.
le Tran
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Y
Department of Pharmacology, University of Toronto, Ontario, Canada.
Forster
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C
D000803:Angiotensin I / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology*; D000805:Angiotensin III / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D066298:In Vitro Techniques; D019808:Losartan / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011945:Receptors, Angiotensin / Q000187:drug effects* / Q000378:metabolism
D000959:Antihypertensive Agents; D010446:Peptide Fragments; D011945:Receptors, Angiotensin; D000804:Angiotensin II; D000805:Angiotensin III; D000803:Angiotensin I; C118790:angiotensin I (1-7); D019808:Losartan; D009638:Norepinephrine