ATTENUATION OF THE EXERCISE PRESSOR REFLEX - EFFECT OF OPIOID AGONIST ON SUBSTANCE-P RELEASE IN L-7 DORSAL HORN OF CATS

Using alpha-chloralose-anesthetized cats, we studied blood pressure and heart rate responses to static contraction and passive stretch of the triceps surae muscle before and after microdialyzing the mu-opioid agonist [D-Ala(2)]-methionine enkephalinamide (DAME, 200 mu mol/L) into the L-7 dorsal horn of the spinal cord. In addition, we measured contraction-induced substance P release in the dorsal horn before and after drug delivery. After 92+/-3 minutes of dialyzing the opioid agonist, contraction-induced increases in mean arterial pressure and heart rate were attenuated from control values of 58+/-7 mm Hg and 17+/-3 beats per minute to postdrug values of 27+/-7 mm Hg and 10+/-2 beats per minute, respectively. A similar attenuation was observed for the passive muscle stretches after 97+/-5 minutes of dialysis (control, 38+/-4 mm Hg and 8+/-2 beats per minute; after drug, 23+/-4 mm Hg and 5+/-1 beats per minute). Prior microdialysis of naloxone (300 mu mol/ L), a mu-antagonist, blocked this effect, suggesting that the opioid agonist has a specific receptor action. Naloxone alone had no effect on the presser or tachycardiac responses. The contraction-induced increase in substance P-like immunoreactivity was reduced from a control value of 0.119+/-0.024 to 0.047+/-0.010 fmol/100 mu L by DAME. Time-control experiments revealed no decrease in the release of substance P-like immunoreactivity. Thus, activation of opioid receptors modulates the transmission of group III and IV muscle afferent nerve activity through the L-7 dorsal horn. Presynaptic inhibition of substance P release from muscle afferents is a potential mechanism of action for DAME.