Modulation of cardiac activity by tachykinins in the rat substantia nigra

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. Increasing doses (25 pmol – 1 nmol) of selective agonists at NK 1 ([Sar 9 ,Met(O 2 ) 11 ]SP), NK 2 ([β‐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. The tachycardia produced by 100 pmol of [β‐Ala 8 ]NKA(4 – 10) or senktide was abolished by an i.v. treatment with atenolol (β 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. 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.British Journal of Pharmacology (2001) 134 , 1749–1759; doi: 10.1038/sj.bjp.0704401