Effects of opioid receptor activation on cardiovascular responses and extracellular monoamines within the rostral ventrolateral medulla during static contraction of skeletal muscle.
During static muscle contraction, activation of opioid receptors alters the extracellular glutamate concentrations within the rostral ventrolateral medulla (RVLM). In addition, microdialysis of glutamate in the ventrolateral medulla (VLM) increases the release of norepinephrine (NE), dopamine (DA), and serotonin (5-HT). Therefore, we hypothesized that extracellular concentrations of these monoamines as well as cardiovascular responses during static skeletal muscle contraction would be modulated following administration of [D-Ala(2)]methionine enkephalinamide (DAME), an opioid receptor agonist, into the RVLM. Microdialysis of 100 microM DAME into the RVLM of 10 rats significantly (P<0.01) decreased extracellular levels (in pg/10 microl) of NE (from 3.3+/-0.3 to 1.9+/-0.3), DA (from 5.5+/-0.2 to 3.7+/-0.3), and 5-HT (from 6.1+/-0.8 to 3.6+/-0.2) during static exercise. After microdialysis of DAME, the exercise pressor reflex also significantly (P<0.01) decreased mean arterial pressure (MAP) by 13+/-3 mmHg and heart rate (HR) by 16+/-6 bpm, compared with control (MAP=22+/-4 mmHg and HR=31+/-7 bpm). Subsequently, after 30 min microdialysis of naloxone, an opioid receptor antagonist, muscle contraction increased the extracellular monoamine levels (in pg/10 microl, 3.8+/-0.3 NE; 5.2+/-0.3 DA; and 5.5+/-0.4 5-HT) similar to the control groups and evoked a reversal of cardiovascular responses. Similarly, 30 min of microdialyzing naloxone, added to the perfusing medium containing DAME, reversed the attenuating effects of DAME on monoamines, MAP, and HR during a muscle contraction. Furthermore, microdialysis of 100 microM naloxone alone for 30 min potentiated cardiovascular responses and monoamine levels during a muscle contraction. In summary, the present data demonstrates that microdialysis of DAME into RVLM attenuates the exercise pressor reflex mediated increases in MAP, HR and extracellular levels of biogenic monoamines. A subsequent microdialysis of naloxone reversed the effects suggesting that an opioidergic mechanism within RVLM modulates the exercise pressor reflex. Overall, the present study provides further insights into the opioidergic modulation of the exercise pressor reflex.
Nauli
S M
SM
Department of Physiology and Pharmacology, Center for Perinatal Biology, Loma Linda University School of Medicine, Loma Linda, CA 92350, USA.
Maher
T J
TJ
Pearce
W J
WJ
Ally
A
A
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D004298:Dopamine / Q000378:metabolism*; D004744:Enkephalin, Methionine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D005110:Extracellular Space / Q000737:chemistry; D005260:Female; D018698:Glutamic Acid / Q000032:analysis / Q000502:physiology*; D006339:Heart Rate / Q000187:drug effects* / Q000502:physiology; D008526:Medulla Oblongata / Q000378:metabolism / Q000503:physiopathology*; D017551:Microdialysis; D009119:Muscle Contraction / Q000187:drug effects* / Q000502:physiology; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011957:Receptors, Opioid / Q000187:drug effects* / Q000502:physiology; D012701:Serotonin / Q000378:metabolism*
D009292:Narcotic Antagonists; D011957:Receptors, Opioid; D012701:Serotonin; D009270:Naloxone; D018698:Glutamic Acid; D004744:Enkephalin, Methionine; C022118:enkephalinamide-Met, Ala(2)-; D004298:Dopamine; D009638:Norepinephrine