Cardioacceleratory responses to hypocretin-1 injections into rostral ventromedial medulla.
Intracisternal injections of hypocretin-1 (hcrt-1) have been shown to elicit sympathoexciatory responses. However, the location of central sites that may mediate these cardiovascular effects have not been clearly elucidated. This study was done in male Wistar rats to investigate the effects of microinjections of hcrt-1 into the rostral ventromedial medulla (RVMM) on mean arterial pressure (MAP), heart rate (HR) and the arterial baroreflex. An initial series of experiments was done to provide a detailed mapping of the location of hcrt-1- and hcrt-1 receptors (hcrtR-1)-like immunoreactivity (i.r.) in the RVMM region. Hcrt-1 and hcrtR-1 ir were found throughout the RVMM region, but primarily within the magnocellular reticular nucleus and the adjacent nucleus paragigantocellularis lateralis. In the second series, this region containing hcrt-1 and hcrtR-1 ir was explored for sites that elicited changes in MAP and HR in the anaesthetized rat. Microinjection of hcrt-1 (0.5-2.5 pmol) into the region of magnocellular reticular nucleus elicited a dose-dependent increase in HR, with little or no change in MAP. Administration (i.v.) of the muscarinic receptor antagonist atropine methyl bromide significantly attenuated ( approximately 62%) the HR response whereas, the total autonomic blockade abolished the HR response. Finally, unilateral or bilateral microinjection of hcrt-1 into the magnocellular reticular nucleus significantly attenuated the reflex bradycardia resulting from the activation of the baroreflex following the increase in MAP from an iv injection of phenylephrine. These data suggest that hcrt-1 in the RVMM region activates neuronal circuits that both inhibit vagal activity and increase sympathetic activity to the heart, and that it alters the excitability of central circuits that reflexly control the circulation.
Department of Physiology and Pharmacology, Faculty of Medicine and Dentistry, Health Sciences Centre, University of Western Ontario, London, ON, Canada N6A 5C1. john.ciriello@fmd.uwo.ca
John
J
Ciriello
Zhaohui
Z
Li
Cleusa V R
CV
de Oliveira
D000818:Animals; D001341:Autonomic Nervous System / Q000502:physiology; D017704:Baroreflex / Q000187:drug effects / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D002352:Carrier Proteins / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects* / Q000502:physiology; D007150:Immunohistochemistry; D007276:Injections, Intraventricular; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects* / Q000502:physiology; D008845:Microinjections; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009479:Neuropeptides / Q000008:administration & dosage / Q000494:pharmacology*; D018733:Nicotinic Antagonists; D064446:Orexin Receptors; D000068797:Orexins; D051381:Rats; D017208:Rats, Wistar; D043562:Receptors, G-Protein-Coupled; D018013:Receptors, Neuropeptide / Q000378:metabolism
D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D018727:Muscarinic Antagonists; D009479:Neuropeptides; D018733:Nicotinic Antagonists; D064446:Orexin Receptors; D000068797:Orexins; D043562:Receptors, G-Protein-Coupled; D018013:Receptors, Neuropeptide