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Evaluation of Cerebral Blood Flow Autoregulation in the Rat Using Laser Doppler Flowmetry
Published on: January 19, 2020
Effect of gamma-melanocyte-stimulating hormones on baroreflex sensitivity and cerebral blood flow autoregulation in
M J Nijsen1, G J de Ruiter, C M Kasbergen
1Department of Medical Pharmacology, Rudolf Magnus Institute for Neurosciences, Utrecht University, Universiteitsweg 100, 3584 CG, Utrecht, The Netherlands. nijsen@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 lysgamma(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 lysgamma(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.
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