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(Circulation Research. 1995;77:326-334.)
© 1995 American Heart Association, Inc.

Articles

Attenuation of the Exercise Pressor Reflex

Effect of Opioid Agonist on Substance P Release in L-7 Dorsal Horn of Cats

André F. Meintjes, Antonio C. L. Nóbrega, Ingbert E. Fuchs, Ahmmed Ally, L. Britt Wilson

From the Harry S. Moss Heart Center, Departments of Internal Medicine and Physiology, University of Texas Southwestern Medical Center at Dallas.

Correspondence to Dr L. Britt Wilson, Harry S. Moss Heart Center, Department of Physiology, UT Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX.

Abstract Using -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 µ-opioid agonist [D-Ala²]-methionine enkephalinamide (DAME, 200 µmol/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 µmol/L), a µ-antagonist, blocked this effect, suggesting that the opioid agonist has a specific receptor action. Naloxone alone had no effect on the pressor 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 µL 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.

Key Words: muscle contraction • presynaptic inhibitory effect • primary afferents • substance P

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