naltrindole and Hypotension

MCRT (YPFPFRTic-NH(2)) is a chimeric opioid peptide based on morphiceptin and PFRTic-NH(2). In order to assess the cardiovascular effect of MCRT, it was administered by intravenous (i.v.) injection targeting at the peripheral nervous system and by intracerebroventricular (i.c.v.) injection targeting at the central nervous system. Naloxone and L-NAME were injected before MCRT to investigate possible interactions with MCRT. Results show that administration of MCRT by i.v. or i.c.v. injection could induce bradycardia and decrease in mean arterial pressure (MAP) at a greater degree than that with morphiceptin and PFRTic-NH(2). When MCRT and NPFF were coinjected, we observed a dose-dependent weakening of these cardiovascular effects by MCRT. Because naloxone completely abolished the cardiovascular effects of MCRT, we conclude that opioid receptors are involved in regulating the MAP of MCRT regardless of modes of injection. The effect of MCRT on heart rate is completely dependent on opioid receptors when MCRT was administered by i.c.v. instead of i.v. The central nitric oxide (NO) pathway is involved in regulating blood pressure by MCRT under both modes of injection, but the peripheral NO pathway had no effect on lowering blood pressure mediated by MCRT when it was administered by i.c.v. Based on the results from different modes of injection, the regulation of heart rate by MCRT mainly involves in the central NO pathway. Lastly, we observed that the cardiovascular effects of MCRT such as bradycardia and decrease of blood pressure, were stronger than that of its parent peptides. Opioid receptors and the NO pathway are involved in the cardiovascular regulation by MCRT, and their degree of involvement differs between intravenous and intracerebroventricular injection.

Topics: Analgesics, Opioid; Animals; Blood Pressure; Bradycardia; Endorphins; Heart Rate; Hypotension; Injections, Intravenous; Injections, Intraventricular; Male; Morphinans; Naloxone; Naltrexone; Narcotic Antagonists; NG-Nitroarginine Methyl Ester; Rats; Rats, Wistar

The aim of the present work was to investigate the role of brain μ, κ and δ opioid receptors in the central serotonergic mechanisms regulating blood pressure in rats. The data obtained show that: (1) pharmacological activation of central 5-HT(3) receptors yields a significant decrease in blood pressure; (2) the blockade of those receptors by a selective antagonist induces an acute hypertensive response; (3) the pharmacological blockade of central opioid receptors by three different opioid antagonists exhibiting variable degrees of selectivity to μ, κ and δ opioid receptors always suppressed the hypotensive response induced by central 5-HT(3) receptor stimulation; (4) the blockade of opioid receptors by the same opioid antagonists that impaired the hypotensive effect of central 5-HT(3) receptor stimulation failed to modify blood pressure in animals not submitted to pharmacological manipulations of central 5-HT(3) receptor function. It is shown that a 5-HT(3) receptor-dependent mechanism seems to be part of the brain serotonergic system that contributes to cardiovascular regulation since the hypertensive response observed after ondansetron administration indicates that central 5-HT(3) receptors exert a tonic inhibitory drive on blood pressure. Furthermore, the data obtained here clearly indicate that the hypotensive response observed after pharmacological stimulation of central 5-HT(3) receptors depends on the functional integrity of brain μ, κ and δ opioid receptors, suggesting that a functional interaction between serotonergic and opiatergic pathways in the brain is part of the complex, multifactorial system that regulates blood pressure in the central nervous system.

Topics: Animals; Biguanides; Blood Pressure; Heart Rate; Hypotension; Male; Naloxone; Naltrexone; Narcotic Antagonists; Ondansetron; Rats; Rats, Wistar; Receptors, Opioid; Receptors, Serotonin, 5-HT3; Serotonin 5-HT3 Receptor Agonists; Serotonin 5-HT3 Receptor Antagonists