Abstract
The mechanism of cardiovascular responses to chemical stimulation of the hypothalamic arcuate nucleus (ARCN) was studied in urethane-anesthetized adult male Wistar rats. At the baseline mean arterial pressure (BLMAP) close to normal, ARCN stimulation elicited decreases in MAP and sympathetic nerve activity (SNA). The decreases in MAP elicited by ARCN stimulation were attenuated by either gamma-aminobutyric acid (GABA), neuropeptide Y (NPY), or beta-endorphin receptor blockade in the ipsilateral hypothalamic paraventricular nucleus (PVN). Combined blockade of GABA-A, NPY1 and opioid receptors in the ipsilateral PVN converted the decreases in MAP and SNA to increases in these variables. Conversion of inhibitory effects on the MAP and SNA to excitatory effects following ARCN stimulation was also observed when the BLMAP was decreased to below normal levels by an infusion of sodium nitroprusside. The pressor and tachycardic responses to ARCN stimulation at below normal BLMAP were attenuated by blockade of melanocortin 3/4 (MC3/4) receptors in the ipsilateral PVN. Unilateral blockade of GABA-A receptors in the ARCN increased the BLMAP and heart rate (HR) revealing tonic inhibition of the excitatory neurons in the ARCN. ARCN stimulation elicited tachycardia regardless of the level of BLMAP. ARCN neurons projecting to the PVN were immunoreactive for glutamic acid decarboxylase 67 (GAD67), NPY, and beta-endorphin. These results indicated that: 1) at normal BLMAP, decreases in MAP and SNA induced by ARCN stimulation were mediated via GABA-A, NPY1 and opioid receptors in the PVN, 2) lowering of BLMAP converted decreases in MAP following ARCN stimulation to increases in MAP, and 3) at below normal BLMAP, increases in MAP and HR induced by ARCN stimulation were mediated via MC3/4 receptors in the PVN. These results provide a base for future studies to explore the role of ARCN in cardiovascular diseases.
Highlights
The hypothalamic arcuate nucleus (ARCN) is located bilaterally adjacent to the floor of the third ventricle
We have previously reported that stimulation of ARCN by microinjections of N-methyl-D-aspartic acid (NMDA) elicits increases in blood pressure (BP), heart rate (HR) and SNA [29]
Microinjections of NMDA (2.5, 5, and 10 mM) into the ARCN elicited the decreases in Mean arterial pressure (MAP) and increases in HR
Summary
The hypothalamic arcuate nucleus (ARCN) is located bilaterally adjacent to the floor of the third ventricle. Gammaaminobutyric acid (GABA) is present in many NPY/AgRP neurons in the ARCN [8,9] These neurons serve orexigenic functions (increase in feeding and decrease in energy expenditure including decrease in sympathetic nerve activity [SNA]). Anorexigenic functions (decrease in feeding and increase in energy expenditure including increase in SNA) are served by neurons containing proopiomelanocortin (POMC) and cocaine and amphetamine-regulated transcript (CART) (POMC/CART neurons) which are located in the ventrolateral ARCN. POMC/CART neurons in the ARCN contain alpha-MSH, beta-endorphin and ACTH [11,12]. Stimulation of POMC/ CART neurons in the ARCN results in the release of one of the excitatory neurotransmitters (alpha-MSH) in the PVN; alphaMSH activates melanocortin receptors (MC3/4 receptors) in the PVN and inhibits food intake and increases energy expenditure and SNA. Leptin and insulin inhibit NPY/AgRP and stimulate POMC/CART neurons [4,15,16]
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