Neuropeptide Y is a prejunctional inhibitor of vagal but not sympathetic inotropic responses in guinea-pig isolated left atria.
1. The effects of NPY and related peptides were examined on basal contractile force and nerve-mediated inotropic responses to electrical field stimulation of the guinea-pig isolated left atrium. 2. Electrical field stimulus (EFS)-inotropic response curves were constructed by applying 1-64 trains of four field pulses (200 Hz, 0.1 ms duration, 100 V) across isolated left atria (paced at 4 Hz, 2 ms, 1-4 V) within the atrial refractory period. Curves were constructed in presence of vehicle, propranolol (1 microM) or atropine (1 microM) to determine appropriate stimulus conditions. 3. The effects of PYY (1-10,000 nM), NPY (0.01-10 microM), N-Ac-[Leu28,31]NPY(24-36) (N-A[L]NPY(24-36); 0.01-10 microM) and clonidine (0.1-1000 nM) were examined on the positive and negative inotropic responses to EFS (eight trains, four pulses per refractory period). 4. NPY-related peptides had no effect on basal force of contraction nor on the inotropic concentration-response curves to bethanechol or isoprenaline. All three peptides inhibited vagally-mediated negative inotropic responses; rank order of potency PYY>NPY> or =N-A[L]NPY(24-36) was consistent with an action at prejunctional Y2-receptors. Clonidine concentration-dependently inhibited sympathetic inotropic responses. However, PYY, NPY and N-A[L]NPY(24-36) failed to mediate any significant inhibition of the positive inotropic response to EFS. 5. These data demonstrate that NPY is an effective inhibitor of vagal but not sympathetically-mediated inotropic responses in the guinea-pig isolated left atria. This may suggest that endogenously co-released NPY is important in mediating cross talk between efferent components of the autonomic nervous system modulating cardiac contractility, acting overall to sustain positive inotropic responses.
Serone
A P
AP
Department of Pharmacology, University of Melbourne, Parkville, Victoria, Australia.
Angus
J A
JA
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002316:Cardiotonic Agents / Q000037:antagonists & inhibitors*; D003000:Clonidine / Q000494:pharmacology; D004558:Electric Stimulation; D005260:Female; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects / Q000294:innervation*; D066298:In Vitro Techniques; D008297:Male; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009200:Myocardial Contraction / Q000187:drug effects*; D009478:Neuropeptide Y / Q000031:analogs & derivatives / Q000494:pharmacology*; D011433:Propranolol / Q000494:pharmacology; D012032:Refractory Period, Electrophysiological / Q000187:drug effects; D013564:Sympathetic Nervous System / Q000187:drug effects*; D009435:Synaptic Transmission / Q000187:drug effects; D014630:Vagus Nerve / Q000187:drug effects*
D000316:Adrenergic alpha-Agonists; D000319:Adrenergic beta-Antagonists; D002316:Cardiotonic Agents; D018727:Muscarinic Antagonists; D009478:Neuropeptide Y; D001285:Atropine; D011433:Propranolol; D003000:Clonidine