Effect of gamma-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 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 intr avenous 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 baro receptor reflex-mediated bradycardia. All tested gamma -MSHs showed a signi ficant impairment of the baroreceptor reflex sensitivity and CBF autoregula tion 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 incr ease in MAP was comparable between the gamma -MSHs and the phenylephrine gr oup. Conclusions: The present study suggests that gamma (2)-MSH and the sho rter fragment gamma (2)-MSH(6-12) impair baroreceptor reflex sensitivity, d ue to a strong increase in sympathetic tone and/or change in baroreceptor r eflex setpoint, and induce cerebrovasodilatation, which can counteract an a utoregulation-mediated cerebrovasoconstriction due to systemic presser effe cts. Furthermore, the results indicate that the C-terminal site of gamma (2 )-MSH is relevant for its central-mediated inhibitory effects on the barore ceptor reflex and CBF. (C) 2001 Elsevier Science B.V. All rights reserved.