Adrenomedullin (ADM), acting through ADM(22-52)-sensitive receptors, is involved in the endotoxin-induced hypotension in rats.
The possible involvement of adrenomedullin (ADM) in the endotoxin-induced hypotension has been investigated in the rat. Lipopolysaccharide (LPS, 500 micrograms/kg intraperitoneum) caused a severe decrease in the blood pressure (BP), reaching maximum 2-3 h after the injection and subsiding after 12 h. The putative ADM-receptor antagonist ADM(22-52) (3 nmol/kg) counteracted LPS-induced BP lowering at 1 and 2 h, and reversed it at 3 and 6 h. CGRP(8-37), a selective antagonist of the CGRP1 receptors, was ineffective. Both ADM(22-52) and CGRP(8-37) did not evoke significant changes in the basal BP. Our findings provide strong support to the view ADM overproduction plays a major role in the LPS-induced decrease in BP, and suggest a potentially important therapeutic effect of the blockade of ADM(22-52)-sensitive receptors during endotoxic shock.
Mazzocchi
G
G
Department of Human Anatomy and Physiology, Section of Anatomy, University of Padua, 35121 Padua, Italy.
Albertin
G
G
Nussdorfer
G G
GG
D053607:Adrenomedullin; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology; D004731:Endotoxins / Q000494:pharmacology*; D007022:Hypotension / Q000139:chemically induced* / Q000503:physiopathology; D066298:In Vitro Techniques; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology*; D010455:Peptides / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D058265:Receptors, Adrenomedullin; D018000:Receptors, Peptide / Q000037:antagonists & inhibitors*
D000959:Antihypertensive Agents; D004731:Endotoxins; D008070:Lipopolysaccharides; D010446:Peptide Fragments; D010455:Peptides; D058265:Receptors, Adrenomedullin; D018000:Receptors, Peptide; C104782:adrenomedullin (22-52); C058636:calcitonin gene-related peptide (8-37); D053607:Adrenomedullin; C044101:endotoxin, Escherichia coli; D015740:Calcitonin Gene-Related Peptide