ROLE OF SPINAL NK1 RECEPTORS IN CARDIOVASCULAR-RESPONSES TO CHEMICAL-STIMULATION OF THE GALLBLADDER

The present study examined the role of substance P (SP) as a sensory n eurotransmitter in cardiovascular responses to bradykinin applied on t he gallbladder. Experiments were performed in anesthetized cats in whi ch sympathetic chains were transected at the T-5-T-6 level, and the ti p of the intrathecal catheter was positioned at T-6-T-7 to limit the i njectate between T-6 and L(2). Bradykinin (10 mu g/ml) was applied ont o the gallbladder before and after intrathecal injection of [D-Pro(2), D-Phe(7),D-Trp(9)]SP (100-200 mu g, NK1/NK2-receptor antagonist), CP-9 9,994 (50-100 mu g, selective NK1 antagonist), MEN-10,376 (100-500 mu g, selective NK2 antagonist), or vehicle. Intrathecal injection of NK1 but not NK2 antagonist significantly reduced increases in mean arteri al pressure, heart rate, and maximal rate of left ventricular pressure change by 28 +/- 2 mmHg (33 +/- 4%), 4 +/- 1 beats/min (42 +/- 5%), a nd 497 +/- 46 mmHg/s (36 +/- 4%), respectively. Intrathecal injection of NK1 or NK1/NK2 antagonist had no effect on cardiovascular responses evoked by electrical stimulation in the rostral ventral lateral medul la. These data suggest that endogenous SP, acting as a sensory neurotr ansmitter, is involved in the excitatory cardiovascular reflex caused by chemical stimulation of the gallbladder through its action on NK1 r eceptors in the spinal cord.