Differential responses to angiotensin-(1-7) in the feline mesenteric and hindquarters vascular beds.
Regional vascular responses to angiotensin (Ang)-(1-7), a heptapeptide derivative of Ang II were investigated in the feline hindquarters and mesenteric vascular beds under conditions of controlled flow. In the mesenteric vascular bed, injections of Ang-(1-7) in doses of 1, 3 and 10 micrograms produced dose-dependent decreases in mesenteric perfusion pressure whereas at doses of 30 and 100 micrograms, increases were observed. In contrast, in the hindquarters circulation, low doses produced increases while high doses produced decreases in perfusion pressure. In both vascular beds the degree of vasoconstriction was weak, being less than 1% of that elicited by Ang II. The vasoconstrictor effect of Ang-(1-7) in both the mesenteric and hindquarters vascular bed was blocked by DuP 753 (1 mg/kg i.v.), an Ang receptor subtype 1 (AT1) antagonist. The vasodilator responses in both vascular beds were partially blocked by the nitric oxide synthase inhibitor, NG-nitro-L-arginine methyl ester (100 mg/kg i.v.) but were unaffected by the cyclooxygenase inhibitor, meclofenamate (2.5 mg/kg i.v.). The present results show that in the peripheral vascular bed of the cat, Ang-(1-7) causes vasodilation or modest vasoconstriction, depending on the dose and the regional vascular bed studied. The present data also suggest that the vasodilator effect of the peptide may be mediated in part by the release of endothelium-derived relaxing factor and the vasoconstrictor effect by activation of the AT1 receptor subtype.
Osei
S Y
SY
Department of Pharmacology, Tulane University School of Medicine, New Orleans, LA 70112.
Ahima
R S
RS
Minkes
R K
RK
Weaver
J P
JP
Khosla
M C
MC
Kadowitz
P J
PJ
D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors; D000803:Angiotensin I; D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000805:Angiotensin III / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000494:pharmacology; D002415:Cats; D006614:Hindlimb / Q000098:blood supply; D007093:Imidazoles / Q000494:pharmacology; D019808:Losartan; D008469:Meclofenamic Acid / Q000494:pharmacology; D017538:Mesenteric Artery, Superior / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester; D019001:Nitric Oxide Synthase; D010446:Peptide Fragments / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D010477:Perfusion; D013777:Tetrazoles / Q000494:pharmacology; D014655:Vascular Resistance / Q000187:drug effects*; D014661:Vasoconstriction / Q000187:drug effects
D001713:Biphenyl Compounds; D007093:Imidazoles; D010446:Peptide Fragments; D013777:Tetrazoles; D000804:Angiotensin II; D000805:Angiotensin III; D008469:Meclofenamic Acid; D000803:Angiotensin I; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; C118790:angiotensin I (1-7); D019808:Losartan; D019331:NG-Nitroarginine Methyl Ester