Neuropeptide W increases mean arterial pressure as a result of behavioral arousal.
Neuropeptide W (NPW), an endogenous ligand for G protein-coupled receptors NPBWR1 (GPR7) and NPBWR2 (GPR8), has been detected in neurons in limbic and reticular activating system areas known to be important in arousal, as well as hypothalamic nuclei known to be important in food and water intake and the neuroendocrine response to stress. In rat, central administration of NPW increased mean arterial pressure (MAP) and behaviors associated with locomotion and grooming. We hypothesized that the NPW-induced increase in MAP was secondary to those increases in physical activity. Since peptides that stimulate arousal have been shown to increase sympathetic activity (e.g., orexin), we tested the ability of the mixed α1- and α2-adrenergic antagonist, phentolamine, to block the NPW-23-induced rise in MAP. Phentolamine pretreatment abrogated the NPW-induced MAP increase. However, we noticed the animals no longer exhibited NPW-associated behavioral arousal when pretreated with phentolamine. Anesthesia also blocked the NPW-induced increase in MAP, although the animals still were able to respond with an increase in MAP to centrally administered ANG II. Additionally, pretreatment with an orexin type 1 receptor antagonist significantly reduced the behavioral action of NPW-23 and completely blocked the peptide's action to increase MAP, suggesting that orexin neurons are downstream targets of NPW. Our results suggest that NPW increased MAP secondary to increased behavioral arousal.
Department of Pharmacological and Physiological Science, Saint Louis University, St. Louis, Missouri.
Alicia T
AT
Pate
Gina L C
GL
Yosten
Willis K
WK
Samson
D058668:Adrenergic alpha-1 Receptor Antagonists / Q000494:pharmacology; D058669:Adrenergic alpha-2 Receptor Antagonists / Q000494:pharmacology; D000758:Anesthesia; D000804:Angiotensin II / Q000008:administration & dosage; D000818:Animals; D001143:Arousal / Q000187:drug effects*; D062186:Arterial Pressure / Q000187:drug effects*; D001522:Behavior, Animal / Q000187:drug effects*; D003243:Consciousness; D006120:Grooming / Q000187:drug effects; D057967:Infusions, Intraventricular; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009479:Neuropeptides / Q000008:administration & dosage / Q000494:pharmacology*; D064446:Orexin Receptors / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors
D058668:Adrenergic alpha-1 Receptor Antagonists; D058669:Adrenergic alpha-2 Receptor Antagonists; C578627:Hcrtr1 protein, rat; D009479:Neuropeptides; D064446:Orexin Receptors; D000804:Angiotensin II
GPR7; GPR8; behavioral arousal; mean arterial pressure; neuropeptide W