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 (A DM) and calcitonin gene-related peptide (CGRP), in the haemodynamic sequela e of continuous infusion of lipopolysaccharide (LPS) was assessed in consci ous, 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) c aused 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 enhance d (by pre-treatment with dexamethasone and the endothelin antagonist, SE 20 9670, or by pretreatment With SE 209670 and the AT(1)-receptor antagonist, losartan), ADM (22-52) had no significant cardiovascular effects. In contra st, the CGRP(1)-receptor antagonist, CGRP (8-37), caused small, but signifi cant, inhibitions of the hypotensive and renal and mesenteric vasodilator e ffects of LPS, but only 6 h after onset of infusion in the presence of dexa methasone and SE 209670. 4 The results indicate that, in this model of endotoxaemia, the marked regi onal vasodilatations seen in the presence of dexamethasone and SE 209670 do not involve ADM, but do involve CGRP, albeit only to a small extent.