TY - JOUR
T1 - Differential responses to angiotensin-(1-7) in the feline mesenteric and hindquarters vascular beds
AU - Osei, Suzette Y.
AU - Ahima, Rexford S.
AU - Minkes, Robert K.
AU - Weaver, Joseph P.
AU - Khosla, Mahesh C.
AU - Kadowitz, Philip J.
N1 - Funding Information:
The authors wish to thank Todd Higuera for technical assistance and Jan Ignarro for editorial assistance. This work was supported by NIH Grant HL15580 and a grant from the American Heart Association.
PY - 1993/3/30
Y1 - 1993/3/30
N2 - Regional vascular responses to angiotensin (Ang)-(1-7), a heptapeptide derivative og Ang II were investigated in the feline hindquarters and mesenteric vascular under conditions of controlled flow. In the mesenteric vascular bed, injections of Ang-(1-7) in doses of 1, 3 and 10 μg produced dose-dependent decreases in mesenteric perfusion pressure whereas at doses of 30 and 100 μg, 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.
AB - Regional vascular responses to angiotensin (Ang)-(1-7), a heptapeptide derivative og Ang II were investigated in the feline hindquarters and mesenteric vascular under conditions of controlled flow. In the mesenteric vascular bed, injections of Ang-(1-7) in doses of 1, 3 and 10 μg produced dose-dependent decreases in mesenteric perfusion pressure whereas at doses of 30 and 100 μg, 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.
KW - Angiotensin receptors
KW - Angiotensin-(1-7)
KW - DuP 753
KW - L-NAME (N-nitro-L-arginine methyl ester)
KW - Nitric oxide synthase
KW - Peptides
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U2 - 10.1016/0014-2999(93)90703-K
DO - 10.1016/0014-2999(93)90703-K
M3 - Article
C2 - 7682513
AN - SCOPUS:0027497895
SN - 0014-2999
VL - 234
SP - 35
EP - 42
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
IS - 1
ER -