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
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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
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↵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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