Premium
Influence of CGRP (8–37), but not adrenomedullin (22–52), on the haemodynamic responses to lipopolysaccharide in conscious rats
Author(s) -
Gardiner S M,
March J E,
Kemp P A,
Bennett T
Publication year - 1999
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0702718
Subject(s) - calcitonin gene related peptide , adrenomedullin , endocrinology , medicine , antagonist , vasodilation , dexamethasone , receptor antagonist , calcitonin , hemodynamics , receptor , neuropeptide
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. 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 ). 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 AT 1 ‐receptor antagonist, losartan), ADM (22–52) had no significant cardiovascular effects. In contrast, the CGRP 1 ‐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. 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.British Journal of Pharmacology (1999) 127 , 1611–1618; doi: 10.1038/sj.bjp.0702718