Substance K: vascular and cardiac effects in rat and pig

The effects of substance K (SK), a newly discovered tachykinin, on the cardiovascular and sympathetic system were evaluated in the pithed rat preparation and in the in situ domestic pig heart. In pithed rats, SK (10 nmol/kg, IV) produced a triphasic mean blood pressure (MAP) response: short depressor, short pressor (+11 +/- 1 mmHg), and prolonged depressor phase (-9 +/- 1 mmHg, n = 9-24, p less than 0.001). Neither effect was significantly affected by pretreatment with propranolol (2 mg/kg) or phentolamine (1 mg/kg). The pressor response was accompanied by increased heart rate (HR): 41 +/- 4 beats/min, while lower doses produced a decrease: -8 +/- 2 beats/min (p less than 0.01). Propranolol abolished the increase in HR. SK inhibited the pressor response evoked by electrical stimulation of the spinal cord (SCS) and by Arg8-vasopressin (AVP). SK increased circulating levels of epinephrine and norepinephrine but did not change release of catecholamines evoked by SCS. Direct intracoronary injections of SK (0.3-100 nmol, intact pig heart) increased coronary blood flow; higher doses decreased MAP and increased HR. These results indicate that: SK can produce pressor and depressor effects in the rat and is a potent coronary dilator in the pig. In the pithed rat SK causes catecholamine release which mediates its cardiac accelerator effect and it antagonizes adrenergic and non-adrenergic pressor stimuli.