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Rostral ventrolateral medullary opioid receptor activation modulates pressor response to muscle contraction
D Caringi1, D J Mokler, D M Koester
1Department of Pharmacology, University of New England College of Osteopathic Medicine, Biddeford, Maine 04005, USA.
Abstract:
The effects of an opioid agonist, [D-Ala2]methionine enkephalinamide (DAME), administered into the rostral ventrolateral medulla (rVLM) or caudal ventrolateral medulla (cVLM) on cardiovascular responses to isometric muscle contraction were determined in anesthetized rats. A 30-s contraction evoked by tibial nerve stimulation increased mean arterial pressure (MAP) and heart rate (HR) by 34 +/- 6 mmHg and 40 +/- 7 beats/min, respectively, with a developed tension of 322 +/- 30 g, after bilateral insertion of microdialysis probes into the rVLM. Thirty-minute dialysis of DAME (10 and 100 microM) attenuated the contraction-evoked cardiovascular changes dose dependently (10 microM: MAP = 25 +/- 4 mmHg, HR = 27 +/- 3 beats/min, tension = 333 +/- 25 g; 100 microM: MAP = 14 +/- 4 mmHg, HR = 16 +/- 5 beats/min, tension = 330 +/- 34 g). Preadministration of an opioid antagonist, naloxone (100 microM), augmented contraction-evoked MAP and HR responses and blocked effects of 100 microM DAME. Microdialysis of DAME into the cVLM produced no changes in the pressor response to contraction. At end of each experiment, tibial nerve stimulation after neuromuscular blockade evoked no MAP or HR change. Results demonstrate that opioid receptor activation within the rVLM modulates cardiovascular responses to isometric muscle contraction.