Melanocortin 3/4 receptors in paraventricular nucleus modulate sympathetic outflow and blood pressure

P Li, BP Cui, LL Zhang, HJ Sun, TY Liu… - Experimental …, 2013 - Wiley Online Library
P Li, BP Cui, LL Zhang, HJ Sun, TY Liu, GQ Zhu
Experimental physiology, 2013Wiley Online Library
New findings• What is the central question of this study? The paraventricular nucleus (PVN)
is important in regulating sympathetic activity and blood pressure. This study addresses
whether activation of melanocortin 3/4 receptors in the PVN modulates sympathetic activity
and blood pressure, and whether intracellular signalling involves the cAMP–protein kinase
A pathway.• What is the main finding and its importance? Activation of melanocortin 3/4
receptors in the PVN increases sympathetic outflow and blood pressure via the cAMP …
New findings
  • • 
    What is the central question of this study?
    The paraventricular nucleus (PVN) is important in regulating sympathetic activity and blood pressure. This study addresses whether activation of melanocortin 3/4 receptors in the PVN modulates sympathetic activity and blood pressure, and whether intracellular signalling involves the cAMP–protein kinase A pathway.
  • • 
    What is the main finding and its importance?
    Activation of melanocortin 3/4 receptors in the PVN increases sympathetic outflow and blood pressure via the cAMP–protein kinase A pathway. Melanocortin 3 receptors in the PVN exert a tonic excitatory effect on sympathetic activity. Melanocortin 3/4 receptors in the PVN are a putative therapeutic target to inhibit sympathetic activity.
Central melanocortin 3/4 receptors (MC3/4Rs) are known to regulate energy balance. Activation of MC3/4Rs causes a greater increase in the firing activity of the PVN neurons in obese Zucker rats than in lean Zucker rats. The present study was undertaken to determine the roles of MC3/4Rs in the hypothalamic paraventricular nucleus (PVN) in modulating the sympathetic activity and blood pressure and its downstream pathway. Renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) were recorded in anaesthetized rats. Microinjection of the MC3/4R agonist melanotan II (MTII) into the PVN increased the RSNA and MAP. The MC3/4R antagonist agouti‐related peptide (AgRP) or SHU9119 decreased the RSNA and MAP, but the MC4R antagonist HS024 had no significant effect on the RSNA and MAP. The effects of MTII were abolished by pretreatment of the PVN with AgRP, SHU9119, the adenylate cyclase inhibitor SQ22536 or the protein kinase A inhibitor Rp‐cAMP, and substantially attenuated by HS024. Microinjection of SQ22536 alone into the PVN had no significant effect on the RSNA and MAP, but Rp‐cAMP caused significant decreases in the RSNA and MAP. Furthermore, MTII increased the cAMP level in the PVN. These results indicate that activation of MC3/4Rs in the PVN increases the sympathetic outflow and blood pressure via the cAMP–protein kinase A pathway. Melanocortin 3 receptors in the PVN may exert a tonic excitatory effect on sympathetic activity.
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