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-IMD(95-147), namely IMD(1-53). The present study was designed to determine the effects of the IMD(1-53) 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 IMD(1-53), intracerebroventricularly or intravenously, respectively, with continuous blood pressure and heart rate monitoring for 45min. Analysis with CGRP receptor antagonist CGRP(8-37), ADM receptor antagonist ADM(22-52), and anti-prepro-IMD antibody showed that 0.1, 0.5, and 1.0 nmol/kg IMD(1-53), caused a dose-dependent elevation in blood pressure, which was more prominent than the increase with equivalent IMD(1-47) or ADM. As well, IMD(1-53) caused a persistent increase in heart rate. The CNS action of IMD(1-53) could be blocked by ADM(22-52), CGRP(8-37), or prepro-IMD antibody. In contrast to the CNS action, intravenous administration of IMD(1-53) induced a depressor effect. These results suggest that IMD(1-53) is an important regulatory factor in mean arterial blood pressure and heart rate through its central and peripheral bioaction.
Ren
Yong-Sheng
YS
Institute of Cardiovascular Disease, Peking University First Hospital, Beijing 100034, China.
Yang
Jing-Hui
JH
Zhang
Jing
J
Pan
Chun-Shui
CS
Yang
Jun
J
Zhao
Jing
J
Pang
Yong-Zheng
YZ
Tang
Chao-Shu
CS
Qi
Yong-Fen
YF
D053607:Adrenomedullin / Q000502:physiology*; D000818:Animals; D001794:Blood Pressure / Q000502:physiology*; D015740:Calcitonin Gene-Related Peptide / Q000502:physiology; D002490:Central Nervous System / Q000502:physiology*; D007106:Immune Sera; D007275:Injections, Intravenous; D007276:Injections, Intraventricular; D009479:Neuropeptides / Q000502:physiology*; D010446:Peptide Fragments / Q000502:physiology*; D051381:Rats
C499411:Adm2 protein, rat; D007106:Immune Sera; D009479:Neuropeptides; D010446:Peptide Fragments; C104782:adrenomedullin (22-52); C058636:calcitonin gene-related peptide (8-37); D053607:Adrenomedullin; D015740:Calcitonin Gene-Related Peptide