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Cardiovascular Research 2001 49(1):226-233; doi:10.1016/S0008-6363(00)00204-2
© 2001 by European Society of Cardiology
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Copyright © 2000, European Society of Cardiology

Effect of {gamma}-melanocyte-stimulating hormones on baroreflex sensitivity and cerebral blood flow autoregulation in rats

Marjoleen J.M.A Nijsen*, Gerrit J.W de Ruiter, Carina M Kasbergen and Dick J de Wildt

Department of Medical Pharmacology, Rudolf Magnus Institute for Neurosciences, Utrecht University, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands

* Corresponding author. Tel.: +31-30-253-3634; fax: +31-30-253-9032 nijsen{at}med.ruu.nl

Objective: In the present paper, we are interested in the effects of {gamma}-melanocyte-stimulating hormones ({gamma}-MSHs) on cardiovascular regulatory systems. Methods: Mean arterial pressure (MAP), cerebral blood flow (CBF) and heart rate (HR) were measured in urethane-anaesthetised rats after intravenous administration of lys{gamma}2-MSH, {gamma}2-MSH, {gamma}2-MSH(6–12) or phenylephrine. Results: The {gamma}-MSHs caused an increase in MAP, CBF and HR, whereas phenylephrine caused an increase in MAP and CBF and baroreceptor reflex-mediated bradycardia. All tested {gamma}-MSHs showed a significant impairment of the baroreceptor reflex sensitivity and CBF autoregulation as compared to the phenylephrine group. {gamma}2-MSH shows identical effects on the baroreceptor reflex and CBF as the endogenous occurring lys{gamma}2-MSH. In addition, the C-terminal fragment of {gamma}2-MSH, {gamma}2-MSH(6–12), induced similar effects as {gamma}2-MSH. The level of increase in MAP was comparable between the {gamma}-MSHs and the phenylephrine group. Conclusions: The present study suggests that {gamma}2-MSH and the shorter fragment {gamma}2-MSH(6–12) impair baroreceptor reflex sensitivity, due to a strong increase in sympathetic tone and/or change in baroreceptor reflex setpoint, and induce cerebrovasodilatation, which can counteract an autoregulation-mediated cerebrovasoconstriction due to systemic pressor effects. Furthermore, the results indicate that the C-terminal site of {gamma}2-MSH is relevant for its central-mediated inhibitory effects on the baroreceptor reflex and CBF.

KEYWORDS Blood pressure; Heart rate (variability); Hormones; Cerebrovascular disorders


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