The hemodynamic effects of gamma 2-melanocyte-stimulating hormone and related melanotropins depend on the arousal potential of the rat.
In conscious rats, i.v. administered adrenocorticotropic hormone (ACTH-(4-10)) and gamma 2-melanocyte-stimulating hormone (gamma 2-MSH) induced a dose-dependent increase in blood pressure (BP), heart rate (HR) and pulse pressure (PP). No circadian influence on these effects was observed. The structurally related peptide, alpha-melanocyte-stimulating hormone (alpha-MSH), only caused an increase in HR, which was not dose-dependent, whereas the stable ACTH-(4-9) analog, Org 2766, was without effect on these hemodynamic parameters. In rats under light urethane-induced anesthesia, which is known to maintain reflexes and sufficient sympathetic tone, gamma 2-MSH caused hemodynamic responses similar to those observed in conscious rats. In contrast, gamma 2-MSH had an opposite effect in rats under deep pentobarbital-induced anesthesia: a depressor effect combined with a slight bradycardia. A comparative study with rats of a more arousable Wistar rat substrain (Riv:TOX) and of a less excitable rat substrain (U:WU) showed that the dose-pressor response curves for ACTH-(4-10) and gamma 2-MSH were shifted to the left in the more excitable rats as compared to the in the less excitable rats. We conclude that a restricted amino acid sequence in the N-terminal part of the pro-opiomelanocortin (POMC)-molecule (gamma 2-MSH/ACTH-(4-10)-like) is responsible for the stimulating effects on the cardiovascular system and that those effects are strongly dependent on the state of arousal, i.e. sympathetic tone, of the rat. These stimulatory effects override a depressor phenomenon which can only be detected during central depression.
De Wildt
D J
DJ
Department of Medical Pharmacology, Rudolf Magnus Institute, Medical Faculty, Utrecht University, Netherlands.
Krugers
H
H
Kasbergen
C M
CM
De Lang
H
H
Versteeg
D H
DH
D000324:Adrenocorticotropic Hormone / Q000031:analogs & derivatives / Q000494:pharmacology*; D000595:Amino Acid Sequence; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D001143:Arousal / Q000187:drug effects*; D001784:Blood Gas Analysis; D001794:Blood Pressure / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D008297:Male; D009074:Melanocyte-Stimulating Hormones / Q000494:pharmacology*; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013045:Species Specificity; D000521:alpha-MSH / Q000494:pharmacology
D000927:Anticonvulsants; D010446:Peptide Fragments; C013765:Org 2766; D000521:alpha-MSH; D000324:Adrenocorticotropic Hormone; D009074:Melanocyte-Stimulating Hormones; C011394:ACTH (4-10)