Hc. Champion et al., ANALYSIS OF RESPONSES TO HUMAN SYNTHETIC ADRENOMEDULLIN AND CALCITONIN-GENE-RELATED PEPTIDES IN THE HINDLIMB VASCULAR BED OF THE CAT, Molecular and cellular biochemistry, 176(1-2), 1997, pp. 5-11
Vasodilator responses to human adrenomedullin (hADM), a newly discover
ed hypotensive peptide, human calcitonin gene related peptide-alpha (h
CGRP-alpha) and hCGRP-beta, which share structural homology with hADM,
were compared in the hindlimb vascular bed of the cat under constant
flow conditions. Injections of hADM (0.003-1 nmol), hCGRP-alpha, and h
CGRP-beta (0.003-0.3 nmol) into the perfusion circuit caused dose-rela
ted decreases in hindlimb perfusion pressure. Vasodilator responses to
hCGRP-alpha and hCGRP-beta were similar in potency and duration, and
the doses of hCGRP-alpha and hCGRP-beta required to reduce hindlimb pe
rfusion pressure 40 mm Hg (ED40 mm Hg) were significantly lower than t
he ED40 mm Hg for hADM. The duration of the hindlimb vasodilator respo
nses to hCGRP-alpha and hCGRP-beta were significantly longer than the
duration of the response to hADM, Amylin, a peptide that shares struct
ural homology with ADM and with CGRP, had no significant effect on hin
dlimb perfusion pressure when injected in doses up to 1 nmol. Decrease
s in hindlimb perfusion pressure in response to hADM, hCGRP-alpha, and
hCGRP-beta were not altered by L-N-5-(1-iminoethyl)-ornithine (L-NIO)
in a dose of the nitric oxide synthase inhibitor that decreased the v
asodilator response to acetylcholine or by the cyclooxygenase inhibito
r, meclofenamate, in a dose that decreased the vasodilator response to
arachidonic acid. The present data demonstrate that hADM, hCGRP-alpha
, and hCGRP-beta have potent, but relatively short-lasting, vasodilato
r activity, and that vasodilator responses are not dependent on the re
lease of nitric oxide or vasodilator prostaglandins in the hindlimb va
scular bed of the cat.