Microinjection of nociceptin (Orphanin FQ) into nucleus tractus solitarii elevates blood pressure and heart rate in both anesthetized and conscious rats

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 activatio n of nociceptin receptors with a unilateral injection of synthetic nocicept in into the NTS, wherein injection of L-glutamate (1 nmol) caused typical d epressor 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 nm ol. 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 nocice ptin receptor antagonist nocistatin (1 nmol) into the NTS abolished the noc iceptin-induced hypertension and tachycardia. In contrast, the nonselective opioid receptor antagonist naloxone (5 nmol) did not modify the cardiovasc ular responses to nociceptin. Intra-NTS injection of nocistatin (0.04 and 1 nmol) and naloxone alone had no significant effect on baseline blood press ure and HR. In chronically cannulated and conscious rats, similar pressor a nd tachycardic responses were induced by intra-NTS injection of 1 nmol of n ociceptin. However, changes in blood pressure and HR were rapid, and quickl y returned to normal levels within 10 min. These data suggest that the newl y discovered nociceptinergic transmission in the NTS has a powerful influen ce on peripheral hemodynamic activity. This influence is inhibitory and may not be tonically active under normal physiological conditions. Moreover, t he cardiovascular responses to exogenous nociceptin were mediated through a ctivation of specific nociceptin receptors rather than typical naloxone-sen sitive opioid receptors.