Characterization of the peripheral action of neuropeptide K on the rat cardiovascular system.
The effects of neuropeptide K (NPK) were measured on mean arterial pressure (MAP) and heart rate (HR) after i.v. injection in urethane-anesthetized rats. NPK (6.5 and 32.5 nmol/kg) produced sustained decreases in MAP and elicited increases in HR. Whereas the NPK-induced tachycardia lasted more than 30 min at 32.5 nmol/kg, a latent and long-lasting bradycardia appeared from 20 min after injection of 6.5 nmol/kg. The initial tachycardia was converted to bradycardia by metoprolol but remained unaffected by hexamethonium, atropine and naloxone. These four treatments, however, prevented the bradycardiac response to NPK at 30 min. Whereas phentolamine, idazoxan, bilateral adrenalectomy and chemical sympathectomy with 6-hydroxydopamine (6-OHDA) preserved the initial tachycardia induced by NPK, they converted the decrease in HR to a tachycardiac response at 30 min. The vasodepressor response to NPK was significantly enhanced by bilateral adrenalectomy, chemical sympathectomy and metoprolol but remained unaffected by all other treatments. Neither the MAP nor the HR responses to NPK were affected by indomethacin. These results suggest that NPK can accelerate HR through non-reflex activation of the sympathoadrenal system. The secondary bradycardia induced by NPK may be due to a vagal reflex while the vasodepressor response to NPK is probably attributable to a direct action mediated by specific receptors on arterial blood vessels. Thus, NPK is considered as the most potent biologically active tachykinin so far described on the rat cardiovascular system.
Décarie
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Département de Physiologie, Faculté de Médecine, Université de Montréal, Qué, Canada.
Couture
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D000315:Adrenalectomy; D000818:Animals; D001337:Autonomic Agents / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects*; D007275:Injections, Intravenous; D008297:Male; D009479:Neuropeptides / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013563:Sympathectomy, Chemical; D015320:Tachykinins
D001337:Autonomic Agents; D009479:Neuropeptides; D015320:Tachykinins; C045206:neuropeptide K