Influence of CGRP (8-37), but not adrenomedullin (22-52), on the haemodynamic responses to lipopolysaccharide in conscious rats.
1. The functional involvement of the vasodilator peptides, adrenomedullin (ADM) and calcitonin gene-related peptide (CGRP), in the haemodynamic sequelae of continuous infusion of lipopolysaccharide (LPS) was assessed in conscious, male, Long Evans rats, by the use of peptide antagonists. 2. It was demonstrated that ADM (22-52) at a dose of 500 nmol kg-1 h-1 caused significant inhibition of the effects of ADM (1 nmol kg-1), without affecting responses to CGRP (0.1 or 1 nmol kg-1). 3. Even when the regional vasodilator responses to LPS infusion were enhanced (by pre-treatment with dexamethasone and the endothelin antagonist, SB 209670, or by pretreatment with SB 209670 and the AT1-receptor antagonist, losartan), ADM (22-52) had no significant cardiovascular effects. In contrast, the CGRP1-receptor antagonist, CGRP (8-37), caused small, but significant, inhibitions of the hypotensive and renal and mesenteric vasodilator effects of LPS, but only 6 h after onset of infusion in the presence of dexamethasone and SB 209670. 4. The results indicate that, in this model of endotoxaemia, the marked regional vasodilatations seen in the presence of dexamethasone and SB 209670 do not involve ADM, but do involve CGRP, albeit only to a small extent.
Gardiner
S M
SM
School of Biomedical Sciences, University of Nottingham Medical School, Queen's Medical Centre, Nottingham NG7 2UH.
March
J E
JE
Kemp
P A
PA
Bennett
T
T
D053607:Adrenomedullin; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology*; D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D003907:Dexamethasone / Q000494:pharmacology; D065128:Endothelin Receptor Antagonists; D004731:Endotoxins / Q000494:pharmacology*; D019453:Escherichia coli O157; D005938:Glucocorticoids / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects*; D007189:Indans / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D019808:Losartan / Q000494:pharmacology; D008297:Male; D010446:Peptide Fragments / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051381:Rats; D020318:Rats, Long-Evans; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D014664:Vasodilation / Q000187:drug effects
D057911:Angiotensin Receptor Antagonists; D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D065128:Endothelin Receptor Antagonists; D004731:Endotoxins; D005938:Glucocorticoids; D007189:Indans; D008070:Lipopolysaccharides; D010446:Peptide Fragments; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; C104782:adrenomedullin (22-52); C087551:1H-Indene-2-carboxylic acid, 1-(1,3-benzodioxol-5-yl)-3-(2- (carboxymethoxy)-4-methoxyphenyl)-2,3-dihydro-5-propoxy-, (1S,2R,3S)-; C058636:calcitonin gene-related peptide (8-37); D053607:Adrenomedullin; C044101:endotoxin, Escherichia coli; D003907:Dexamethasone; D015740:Calcitonin Gene-Related Peptide; D019808:Losartan