Naloxone potentiation of cardiovascular responses to sympathomimetic amines in the rat.
The work was aimed at analyzing the ability of naloxone to potentiate 1) the arterial pressure responses to sympathomimetic amines administered i.v. in normotensive anesthetized, pithed, chemically sympathectomized or acutely adrenalectomized rats and 2) the chronotropic responses to norepinephrine in the isolated rat atria. In anesthetized rats, naloxone (2.5-10 mg/kg i.v.) potentiated the pressor responses to epinephrine (2 micrograms/kg). Naloxone (5 mg/kg) significantly potentiated the pressor responses to norepinephrine (1-4 micrograms/kg), phenylephrine (10-50 micrograms/kg) and the reflex pressor responses to a 60-sec carotid occlusion. On the contrary, naloxone did not potentiate the arterial pressure responses to methoxamine (100 micrograms/kg), angiotensin (0.5-2 micrograms/kg) and isoproterenol (1 micrograms/kg). Pithing or acute adrenalectomy did not alter the naloxone-induced potentiation of the pressor responses to norepinephrine (0.125-0.5 micrograms/kg). 6-Hydroxydopamine pretreatment abolished completely the naloxone-induced potentiation of the pressor responses to norepinephrine (0.25-1 micrograms/kg). In isolated rat atria, naloxone (1.4 and 2.8 x 10(-5) M) potentiated the chronotropic responses to norepinephrine (1.5-6 x 10(-8) M). It is suggested that naloxone potentiates cardiovascular responses to sympathomimetic amines by interacting with presynaptic adrenergic mechanisms which could additionally contribute to its pressor effects in acute hypotensive conditions.
Feria
M
M
Department of Pharmacology, Faculty of Medicine, University of La Laguna, Tenerife, Spain.
Alvarez
C
C
Domínguez
J
J
Sánchez
A
A
Boada
J
J
D000809:Angiotensins / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D004357:Drug Synergism; D006339:Heart Rate / Q000187:drug effects*; D008297:Male; D009270:Naloxone / Q000494:pharmacology*; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000187:drug effects; D017465:Receptors, Opioid, delta; D013566:Sympathomimetics / Q000494:pharmacology*
D000809:Angiotensins; D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; D013566:Sympathomimetics; D009270:Naloxone; D009638:Norepinephrine