Exogenous NPY modulation of cardiac autonomic reflexes and its pressor effect in the conscious rabbit.
1. Neuropeptide Y (NPY) may inhibit sympathetic and vagal transmission via presynaptic Y2 receptors and cause vasoconstriction via postsynaptic Y1 receptors. We examined the effects of NPY and related peptides on cardiovascular parameters and autonomic reflexes in the conscious rabbit. Further, the postjunctional effects of NPY and related peptides were assessed on acetylcholine (ACh) and isoprenaline agonist dose-chronotropic response curves. 2. In conscious rabbits the cardiac baroreceptor-heart rate reflex (baroreflex), Bezold-Jarisch like and nasopharyngeal reflexes were assessed in control, propranolol-treated or methscopolamine-treated (baroreflex only) groups, before and 30 min after i.v. administration of NPY (10 microg kg[-1] + 5 microg kg[-1] min[-1]) or vehicle (saline, 10 ml h[-1]). The effects of equivalent pressor doses of [Leu31, Pro34]NPY or methoxamine on the baroreflex were also examined. In separate animals, dose-heart rate (HR) response curves to isoprenaline or ACh were constructed before and 15 min after administration of NPY, [Leu31,Pro34]NPY (ACh only) or [Leu31,Pro34]NpY + sodium nitroprusside (ACh only). 3. Administration of NPY-receptor agonists caused sustained bradycardia (in the absence of methscopolamine) and rightward shifts of the barocurves in all 3 groups. The range of sympathetically-mediated tachycardia was significantly decreased by NPY or [Leu31,Pro34]NPY in the methscopolamine-treated group. However, these changes in the baroreflex were no different from those elicted by equipressor doses of methoxamine. There was no vagal inhibition by any NPY-receptor agonist in all three autonomic reflexes examined. ACh or isoprenaline dose-HR response curves were not affected by NPY peptide administration. 4. We conclude that in the conscious rabbit, at a single dose that elicits a significant pressor response, exogenous NPY has no direct effect on modulation of cardiac and autonomic reflexes. Non-specific effects of exogenous NPY on the baroreflex may be fully explained by its pressor action. There was no effect of NPY on postjunctional ACh or isoprenaline agonist dose-response curves. Therefore, it is unlikely that endogenous NPY has a functional role in directly modulating cardiac autonomic neurotransmission in the rabbit.
Serone
A P
AP
Department of Pharmacology, University of Melbourne, Parkville, Victoria, Australia.
Angus
J A
JA
Wright
C E
CE
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D001341:Autonomic Nervous System / Q000187:drug effects*; D001794:Blood Pressure / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects*; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008729:Methoxamine / Q000494:pharmacology; D009305:Nasopharynx / Q000187:drug effects / Q000502:physiology; D009478:Neuropeptide Y / Q000031:analogs & derivatives / Q000494:pharmacology*; D011311:Pressoreceptors / Q000187:drug effects; D011817:Rabbits; D012018:Reflex / Q000187:drug effects*
D000318:Adrenergic beta-Agonists; D009478:Neuropeptide Y; D008729:Methoxamine; D007545:Isoproterenol