Intermedin 1-53 in central nervous system elevates arterial blood pressure in rats

Intermedin (IMD) is a novel member of the calcitonin/calcitonin gene-related peptide (CGRP) family identified from human and other vertebrate tissues. Preprointermedin can generate various mature peptides by proteolytic cleavage. Amino acid sequence analysis showed cleavage sites located between two basic amino acids at Arg93-Arg94 resulting in the production of prepro-IMD95-147, namely IMD1-53. The present study was designed to determine the effects of the IMD1-53 fragment in the central nervous system (CNS) on mean arterial blood pressure and heart rate in normal rats and its possible mechanism. Rats were given doses of adrenomedullin (ADM) or IMD1-53, intracerebroventricularly or intravenously, respectively, with continuous blood pressure and heart rate monitoring for 45 min. Analysis with CGRP receptor antagonist CGRP8-37, ADM receptor antagonist ADM22-52, and anti-prepro-IMD antibody showed that 0.1, 0.5, and 1.0 nmol/kg IMD1-53, caused a dose-dependent elevation in blood pressure, which was more prominent than the increase with equivalent IMD1-47 or ADM. As well, IMD1-53 caused a persistent increase in heart rate. The CNS action of IMD1-53 could be blocked by ADM22-52, CGRP8-37, or prepro-IMD antibody. In contrast to the CNS action, intravenous administration of IMD1-53 induced a depressor effect. These results suggest that IMD1-53 is an important regulatory factor in mean arterial blood pressure and heart rate through its central and peripheral bioaction.