Central mechanisms for the hypertensive effects of preproadrenomedullin-derived peptides in conscious rats.
Peptides derived from postranslational processing of preproadrenomedullin exert potent hypotensive effects in the periphery. One of those peptides, adrenomedullin (AM) also has been demonstrated to act centrally in conscious rats to inhibit water drinking and salt appetite and, in anesthetized rats, surprisingly to increase blood pressure. We examined the effects of AM and the other postranslational product, proadrenomedullin NH2-terminal 20 peptide (PAMP), on blood pressure in conscious rats. Both AM and PAMP elicited dose-related increases in mean arterial pressure after cerebroventricular administration. The hypertensive effects of both AM and PAMP and of ANG II were blocked by peripheral administration of phentolamine, indicating actions of the peptides in brain to stimulate sympathetic nervous system function. Blockade of central ANG II receptors with saralasin prevented the hypertensive effects of both ANG II and PAMP, suggesting recruitment of endogenous angiotensinergic systems by central PAMP. The structural homolog of AM, calcitonin gene-related peptide (CGRP), at similar doses did nto significantly affect blood pressure. Furthermore, the hypertensive effects of ANG II, AM, and PAMP were not abrogated by prior administration of the CGRP antagonist. We hypothesize that AM and PAMP exert cardioprotective effects in brain, which may counterbalance the volume-unloading actions of the peptides in the periphery.
Samson
W K
WK
Department of Physiology, University of North Dakota School of Medicine, Grand Forks 58202-9037, USA.
Murphy
T C
TC
Resch
Z T
ZT
D053607:Adrenomedullin; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology*; D002316:Cardiotonic Agents / Q000494:pharmacology*; D002490:Central Nervous System / Q000502:physiology*; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology*; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*; D011506:Proteins / Q000494:pharmacology*; D051381:Rats; D014665:Vasodilator Agents / Q000494:pharmacology*
D002316:Cardiotonic Agents; D010446:Peptide Fragments; D010455:Peptides; D011506:Proteins; D014665:Vasodilator Agents; D053607:Adrenomedullin