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

Objective: In the present paper, we are interested in the effects of γ-melanocyte-stimulating hormones (γ-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 lysγ2-MSH, γ2-MSH, γ2-MSH(6–12) or phenylephrine. Results: The γ-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 γ-MSHs showed a significant impairment of the baroreceptor reflex sensitivity and CBF autoregulation as compared to the phenylephrine group. γ2-MSH shows identical effects on the baroreceptor reflex and CBF as the endogenous occurring lysγ2-MSH. In addition, the C-terminal fragment of γ2-MSH, γ2-MSH(6–12), induced similar effects as γ2-MSH. The level of increase in MAP was comparable between the γ-MSHs and the phenylephrine group. Conclusions: The present study suggests that γ2-MSH and the shorter fragment γ2-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 γ2-MSH is relevant for its central-mediated inhibitory effects on the baroreceptor reflex and CBF.