(pro11,d-ala12)-angiotensin i has rapid onset vasoconstrictor
activity in the cat.
Garrison, Etoi A., Hunter C. Champion, and Philip J. Kadowitz.
Department of Pharmacology, Tulane University School of Medicine,
New Orleans, Louisiana 70112
APStracts 4:0183E, 1997.
Responses to the synthetic substrate (Pro11,D-Ala12)-angiotensin I
were investigated in the hindlimb vascular bed of the cat, a system
in which local angiotensin converting enzyme activity is high. Under
constant-flow conditions, injections of (Pro11,D-Ala12)-angiotensin I
into the perfusion circuit in doses of 1-300 [mu]g caused dose
-related increases in perfusion pressure that were rapid in onset and
that were not changed by the presence of a time-delay coil in the
perfusion circuit upstream from the site of peptide injection. The
synthetic substrate was approximately 100-fold less potent than
angiotensin I and II, and responses to (Pro11,D-Ala12)-angiotensin I
were not altered by captopril in a dose that inhibited pressor
responses to angiotensin I but did not alter responses to angiotensin
II. Responses to (Pro11,D-Ala12)-angiotensin I, angiotensin I, and
angiotensin II were inhibited by DuP 532 and candesartan but were not
altered by the AT2 receptor antagonist PD 123,319. The present data
show that (Pro11,D-Ala12)-angiotensin I has significant
vasoconstrictor activity in the hindlimb vascular bed of the cat and
suggest that responses are mediated by the activation of AT1
receptors, and that activation of AT2 receptors is not involved. The
present data show that the onset of responses to (Pro11,D-Ala12)
-angiotensin I and angiotensin II are similar and are not dependent on
the action of the angiotensin-converting enzyme. The present data
suggest that conversion of the synthetic substrate to an active
peptide occurs rapidly within the hindlimb vascular bed or that the
peptide may have direct AT1-receptor stimulating activity.
Received 24 April 1997; accepted in final form 7 August 1997.
APS Manuscript Number E186-7.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1997 The American Physiological Society.
Published in APStracts on 27 August 1997