Effect of gamma 2-melanocyte-stimulating hormone on cerebral blood flow in rats.
The effects of the proopiomelanocortin-(POMC)-derived peptide gamma 2-melanocyte-stimulating hormone (gamma 2-MSH) on mean arterial blood pressure (BP: MAP), heart rate (HR), internal and total carotid blood flow (BF) (CFint and CFtot, respectively), and regional cerebrocortical blood flow (CBF) were measured in urethane-anesthetized rats after intravenous (i.v.) and intracarotid (i.car.) administration of the peptide. gamma 2-MSH (1.5-100 nmol/kg) administered i.v. and i.car. caused a dose-dependent increase in MAP and HR. Injection of the peptide i.car. in the middose range resulted in a more pronounced pressor effect. Furthermore, the earlier onset of the hemodynamic effects after i.car. injection suggests that forebrain structures play a role in these effects. In addition to the pressor response, gamma 2-MSH produced a strong increase in CFint, CFtot, and CBF after both routes of administration, suggesting an increased intracerebral BF. Whereas the effects of the higher doses of gamma 2-MSH on MAP and CFtot were quantitatively comparable after either the intravenous or intracarotid administration, the effect on regional CBF and CFint was about twice as high after i.car. infusion, indicating a centrally mediated phenomenon underlying this effect on CBF. The increase in CFint cannot in itself be ascribed to a gamma 2-MSH-mediated higher perfusion pressure (i.e., BP), since an equipressor dose of norepinephrine (NE) caused a significant decrease in CFint. The significant and more than twofold higher increase in CBF after intracarotid administration of gamma 2-MSH in comparison with administration of NE by the same route also suggests a central origin for the enhancement of microcirculatory flow due to the peptide.
de Wildt
D J
DJ
Department of Medical Pharmacology, Rudolf Magnus Institute for Neurosciences, Medical Faculty, Utrecht University, The Netherlands.
Kasbergen
C M
CM
Versteeg
D H
DH
D000818:Animals; D001784:Blood Gas Analysis; D001794:Blood Pressure / Q000187:drug effects*; D002339:Carotid Arteries / Q000187:drug effects / Q000502:physiology; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects*; D007269:Injections, Intra-Arterial; D007275:Injections, Intravenous; D017078:Laser-Doppler Flowmetry; D008297:Male; D009074:Melanocyte-Stimulating Hormones / Q000008:administration & dosage / Q000494:pharmacology*; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D014662:Vasoconstrictor Agents; D009074:Melanocyte-Stimulating Hormones; D009638:Norepinephrine