Adrenomedullin binding improves catecholamine responsiveness and kidney function in resuscitated murine septic shock
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.