The central distribution of adrenomedullin and its effects on blood pressure and heart rate in rats.
The present study was designed to make certain whether there exists adrenomedullin (ADM) in the rat central nervous system and evaluated the hemodynamic actions of intracerebroventricular administration (ICVA) of human ADM[13-52]. By immunohistochemistry (ABC method). We found that there was a discrete localization of ADM-positive immunoreactivity in the rat central system including cerebral cortex, paraventricular tissues, hypothalamus, cerebella cortex, mesencephalon and medulla oblongata. By reverse transcription-polymerase chain reaction (RT-PCR) analysis, rat ADM mRNA was found to be expressed in rat brain. These above results of immunohistochemistry and RT-PCR suggest that ADM exists in the rat brain. We also found that centrally administered ADM[13-52] in a dose of 0.4 to 3.2 nmol/kg provoked marked, prolonged and dose-dependent increases in mean arterial blood pressure (MABP) and heart rate (HR). To clarify the mechanisms of the hemodynamic changes induced by centrally administered ADM [13-52], the effect of centrally administered ADM[13-52] on renal sympathetic nerve activity (RSNA) was studied. The result showed that centrally administered ADM [13-52] (1.6 nmol/kg) provoked a marked increase in RSNA, therefore, the increases in MABP and HR induced by centrally administered ADM [13-52] might be due to the stimulation of central sympathetic mechanism. In addition, we also compared the relationship of activity and structure among the different fragments of ADM. In conclusion, ADM exists in the rat brain, and it may play an important role in the central control of cardiovascular system.
Wei
Y
Y
Department of Physiology, Institute of Basic Medicine, Hebei Medical College, Shijiazhuang.
Li
Q
Q
Song
L
L
Zhao
D
D
Zhang
Z
Z
He
R
R
Tang
J
J
D053607:Adrenomedullin; D000818:Animals; D000959:Antihypertensive Agents / Q000493:pharmacokinetics* / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D001923:Brain Chemistry; D006339:Heart Rate / Q000187:drug effects*; D007150:Immunohistochemistry; D007276:Injections, Intraventricular; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology; D010455:Peptides / Q000493:pharmacokinetics* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar
D000959:Antihypertensive Agents; D010446:Peptide Fragments; D010455:Peptides; D053607:Adrenomedullin