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Research ArticleNEUROPHARMACOLOGY

Microinjection of Nociceptin (Orphanin FQ) into Nucleus Tractus Solitarii Elevates Blood Pressure and Heart Rate in Both Anesthetized and Conscious Rats

Limin Mao and John Q. Wang
Journal of Pharmacology and Experimental Therapeutics July 2000, 294 (1) 255-262;
Limin Mao
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Abstract

The role of nociceptinergic transmission in the nucleus tractus solitarii (NTS) in the central modulation of cardiovascular activity was investigated in pentobarbital-anesthetized and conscious rats. Pharmacological activation of nociceptin receptors with a unilateral injection of synthetic nociceptin into the NTS, wherein injection ofl-glutamate (1 nmol) caused typical depressor responses, elevated blood pressure and heart rate (HR) in most of the anesthetized rats. The elevation of blood pressure and HR by nociceptin was dose-dependent (0.04, 0.2, and 1 nmol) with a threshold dose of 0.2 nmol. At 1 nmol, changes in blood pressure and HR were evident at 5 min, and remained for 45 min after injection. Pretreatment with the selective nociceptin receptor antagonist nocistatin (1 nmol) into the NTS abolished the nociceptin-induced hypertension and tachycardia. In contrast, the nonselective opioid receptor antagonist naloxone (5 nmol) did not modify the cardiovascular responses to nociceptin. Intra-NTS injection of nocistatin (0.04 and 1 nmol) and naloxone alone had no significant effect on baseline blood pressure and HR. In chronically cannulated and conscious rats, similar pressor and tachycardic responses were induced by intra-NTS injection of 1 nmol of nociceptin. However, changes in blood pressure and HR were rapid, and quickly returned to normal levels within 10 min. These data suggest that the newly discovered nociceptinergic transmission in the NTS has a powerful influence on peripheral hemodynamic activity. This influence is inhibitory and may not be tonically active under normal physiological conditions. Moreover, the cardiovascular responses to exogenous nociceptin were mediated through activation of specific nociceptin receptors rather than typical naloxone-sensitive opioid receptors.

Footnotes

  • Send reprint requests to: John Q. Wang, Ph.D., Division of Pharmacology, School of Pharmacy, University of Missouri-Kansas City, 2411 Holmes St., Kansas City, MO 64108. E-mail: wangjq{at}umkc.edu

  • ↵1 This study was supported by the American Heart Association-Heartland Affiliate (99-6-0266Z) and the National Institute on Drug Abuse/National Institutes of Health (DA10355).

  • Abbreviations:
    ORL1
    opioid receptor-like 1
    ABP
    arterial blood pressure
    RVL
    rostral ventrolateral medulla
    NTS
    nucleus tractus solitarii
    HR
    heart rate
    PE
    polyethylene
    MAP
    mean arterial pressure
    bpm
    beats per min
    • Received December 23, 1999.
    • Accepted March 14, 2000.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 294 (1)
Journal of Pharmacology and Experimental Therapeutics
Vol. 294, Issue 1
1 Jul 2000
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Research ArticleNEUROPHARMACOLOGY

Microinjection of Nociceptin (Orphanin FQ) into Nucleus Tractus Solitarii Elevates Blood Pressure and Heart Rate in Both Anesthetized and Conscious Rats

Limin Mao and John Q. Wang
Journal of Pharmacology and Experimental Therapeutics July 1, 2000, 294 (1) 255-262;

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Research ArticleNEUROPHARMACOLOGY

Microinjection of Nociceptin (Orphanin FQ) into Nucleus Tractus Solitarii Elevates Blood Pressure and Heart Rate in Both Anesthetized and Conscious Rats

Limin Mao and John Q. Wang
Journal of Pharmacology and Experimental Therapeutics July 1, 2000, 294 (1) 255-262;
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