Modulation of cardiac activity by tachykinins in the rat substantia nigra.
1. The effects of tachykinin NK(1), NK(2) and NK(3) receptor agonists and antagonists were measured on blood pressure (MAP) and heart rate (HR) after bilateral microinjection into the substantia nigra (SN) of awake, unrestrained rats. 2. Increasing doses (25 pmol - 1 nmol) of selective agonists at NK(1) ([Sar(9),Met(O(2))(11)]SP), NK(2) ([beta-Ala(8)]NKA(4 - 10)) and NK(3) (senktide) receptors into the SN produced tachycardia which was selectively and reversibly blocked by the prior injection of tachykinin antagonists at NK(1) (RP67580, 250 pmol), NK(2) (SR48968, 250 pmol) and NK(3) (R-820, 500 pmol) receptor. A rapid fall in MAP followed by a pressor response was seen with 1 nmol of [Sar(9),Met(O(2))(11)]SP. Behavioural activity was elicited by 1 nmol of [Sar(9),Met(O(2)(11)]SP (sniffing > face washing = grooming) and senktide (sniffing > wet dog shake > rearing = locomotion). Tachykinin antagonists had no direct cardiovascular or behavioural effects. 3. The tachycardia produced by 100 pmol of [beta-Ala(8)]NKA(4 - 10) or senktide was abolished by an i.v. treatment with atenolol (beta(1)-adrenoceptor antagonist, 5 mg kg(-1)) while that evoked by [Sar(9),Met(O(2))(11)]SP was reduced. A combination of atenolol (5 mg kg(-1)) and atropine (muscarinic antagonist, 1 mg kg(-1)) blocked the response evoked by [Sar(9),Met(O(2))(11)]SP. 4. These data suggest that the SN is a potential site of modulation of cardiac activity by tachykinins. In addition to the withdrawal of the cardiovagal activity by NK(1) receptor, the three tachykinin receptors appear to increase the sympatho/adrenal drive to the heart. This occurs independently of changes in MAP and behaviour. Hence, this study highlights a new central regulatory mechanism of cardiac autonomic activity.
Lessard
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A
Département de Physiologie, Faculté de Médecine, Université de Montréal C.P. 6128, Succursale centre-ville, Montréal, Québec, Canada.
Couture
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R
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001262:Atenolol / Q000008:administration & dosage / Q000494:pharmacology; D001285:Atropine / Q000008:administration & dosage / Q000494:pharmacology; D001549:Benzamides / Q000008:administration & dosage / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D007211:Indoles / Q000008:administration & dosage / Q000494:pharmacology; D054833:Isoindoles; D008297:Male; D008845:Microinjections; D018727:Muscarinic Antagonists / Q000494:pharmacology; D064729:Neurokinin-1 Receptor Antagonists; D009842:Oligopeptides / Q000008:administration & dosage / Q000494:pharmacology; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology; D010880:Piperidines / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018040:Receptors, Neurokinin-1 / Q000819:agonists; D018041:Receptors, Neurokinin-2 / Q000819:agonists / Q000037:antagonists & inhibitors; D018042:Receptors, Neurokinin-3 / Q000819:agonists / Q000037:antagonists & inhibitors; D018039:Receptors, Tachykinin / Q000819:agonists* / Q000037:antagonists & inhibitors; D013373:Substance P / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D013378:Substantia Nigra / Q000187:drug effects*; D013610:Tachycardia / Q000188:drug therapy; D015320:Tachykinins / Q000494:pharmacology*
D000319:Adrenergic beta-Antagonists; D001549:Benzamides; D007211:Indoles; D054833:Isoindoles; D018727:Muscarinic Antagonists; D064729:Neurokinin-1 Receptor Antagonists; D009842:Oligopeptides; D010446:Peptide Fragments; D010880:Piperidines; C109443:R 820; D018040:Receptors, Neurokinin-1; D018041:Receptors, Neurokinin-2; D018042:Receptors, Neurokinin-3; D018039:Receptors, Tachykinin; D015320:Tachykinins; C054724:senktide; C071693:7,7-diphenyl-2-(1-imino-2-(2-methoxyphenyl)ethyl)perhydroisoindol-4-one; D013373:Substance P; D001262:Atenolol; C073839:SR 48968; D001285:Atropine