Investigation of the central sites at which morphine acts to cause hypertension in conscious rabbits.
1. In conscious rabbits intracerebroventricular (i.c.v.) morphine (10 and 50 micrograms kg-1) caused a dose-related increase in plasma noradrenaline and adrenaline, respiratory depression and sedation. The increase in sympatho-adrenal outflow resulted in hypertension accompanied by bradycardia and the increase in adrenaline secretion caused hyperglycaemia. Morphine (1 microgram kg-1 i.c.v.) and i.c.v. saline had no effect. 2. The same doses of morphine given intracisternally (i.c.) caused bradycardia and a similar degree of respiratory depression to i.c.v. morphine, but no significant increase in blood pressure and only a small, gradual rise in plasma adrenaline. 3. Intravenous naloxone (1 mg kg-1) did not block the hypertension, hyperglycaemia or increase in plasma catecholamines that followed i.c.v. morphine, but prevented the respiratory depression and sedation. 4. Ganglionic blockade with pentolinium prevented the rise in plasma catecholamines, blood pressure and plasma glucose induced by i.c.v. morphine. 5. These findings demonstrate that the increased sympathoadrenal outflow following i.c.v. morphine results from an action on periventricular structures. The resultant increase in plasma catecholamines, which is largely naloxone resistant, accounts for the hypertension and hyperglycaemia. The bradycardia is probably partly baroflex mediated and partly due to an increase in vagal tone as a result of stimulation of brainstem opioid receptors. The respiratory depression is probably due to an action of morphine on brainstem opioid receptors.
May
C N
CN
Department of Medicine, St. Mary's Hospital Medical School, London.
Whitehead
C J
CJ
Dashwood
M R
MR
Mathias
C J
CJ
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D002395:Catecholamines / Q000097:blood; D002946:Cisterna Magna; D005730:Ganglionic Blockers / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000139:chemically induced* / Q000503:physiopathology; D007267:Injections; D007276:Injections, Intraventricular; D008297:Male; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology*; D009270:Naloxone / Q000494:pharmacology; D010101:Oxygen Consumption / Q000187:drug effects; D011817:Rabbits; D011957:Receptors, Opioid / Q000187:drug effects*
D001786:Blood Glucose; D002395:Catecholamines; D005730:Ganglionic Blockers; D011957:Receptors, Opioid; D009270:Naloxone; D009020:Morphine