Contrasting influences of central and peripheral opioids on cardiac baroreflex sensitivity in rabbits.
We studied the effects of naloxone [0.1 mg/kg intravenously (i.v.) or 7.5 micrograms/kg intracisternally (i.c.)], naloxone methyl iodide (NMI, 0.2 mg/kg, i.v. or 15 micrograms/kg i.c.) and morphine (2 mg/kg i.v.) on the cardiac baroreflex elicited in conscious rabbits especially bred for high and low baroreflex sensitivity (BRS) (group I, BRS > 5.5 beats/min/mm Hg and group II BRS < 4 beats/min/mm Hg, respectively). Full sigmoid barocurves were produced in 37 rabbits by i.v. injection of phenylephrine (1-15 micrograms/kg) and nitroglycerin (1-20 micrograms/kg) after pretreatment with saline or one of the above drugs. In group I, both naloxone i.v. and i.c. and NMI i.c. significantly reduced BRS and decreased the degree of bradycardia in response to a pressor stimulus; neither morphine nor NMI i.v. had any effect. In group II, naloxone i.v. and i.c. and NMI i.c. had no effect on BRS, but both morphine and NMI i.v. significantly increased BRS. An even greater increase was achieved by a combination of these drugs, which also increased specifically the degree of tachycardia in response to a decrease in blood pressure (BP). The results suggest that baroreceptor activation in group I released in the brainstem an opioid peptide that acts to increase BRS. In contrast, group II rabbits responded by peripheral opioid activation, which results in a decrease in BRS, possibly by inhibiting norepinephrine (NE) release from cardiac neurons. The predominance of peripheral or central opioid involvement in BRS modulation appears to be due to genetic factors.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D002946:Cisterna Magna / Q000187:drug effects; D005260:Female; D006339:Heart Rate / Q000187:drug effects*; D007275:Injections, Intravenous; D008297:Male; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology*; D009270:Naloxone / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology*; D005996:Nitroglycerin / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011311:Pressoreceptors / Q000187:drug effects* / Q000502:physiology; D000644:Quaternary Ammonium Compounds; D011817:Rabbits; D011957:Receptors, Opioid / Q000187:drug effects* / Q000502:physiology
D000644:Quaternary Ammonium Compounds; D011957:Receptors, Opioid; D010656:Phenylephrine; D009270:Naloxone; C041269:N-methylnaloxone; D009020:Morphine; D005996:Nitroglycerin