Evidence that intravenous morphine stimulates central opiate receptors to increase sympatho-adrenal outflow and cause hypertension in conscious rabbits.
1. In conscious rabbits, intravenous morphine caused hypertension, bradycardia, hyperglycaemia and increased plasma adrenaline and noradrenaline. These effects were prevented by ganglionic blockade with pentolinium. 2. The cardiovascular responses to morphine were not altered by pretreatment with a vasopressin V1-receptor antagonist. 3. After bilateral adrenalectomy morphine caused a similar rise in noradrenaline but no increase in adrenaline. The rise in blood pressure was attenuated and the hyperglycaemia was abolished. 4. Adrenaline infused intravenously to mimic the levels that occurred after morphine caused a similar degree of hyperglycaemia but only a small increase in blood pressure. 5. Pretreatment with intracerebroventricular naloxone prevented the morphine-induced hypertension, hyperglycaemia, increase in plasma catecholamines, respiratory depression and sedation. 6. These results demonstrate that, in conscious rabbits, intravenous morphine causes hypertension by increasing sympathetic vasoconstrictor nerve activity and elevating plasma adrenaline levels; the latter alone produces the hyperglycaemia. Vasopressin release is not involved in the hypertensive response to morphine. The effects of morphine appear to result from stimulation of central opiate receptors leading to enhanced sympathoadrenal outflow.
May
C N
CN
Medical Unit, St Mary's Hospital Medical School, London.
Whitehead
C J
CJ
Heslop
K E
KE
Mathias
C J
CJ
D000315:Adrenalectomy; D000818:Animals; D001127:Arginine Vasopressin / Q000031:analogs & derivatives / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D004837:Epinephrine / Q000008:administration & dosage / Q000097:blood; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000139:chemically induced*; D007262:Infusions, Intravenous; D007276:Injections, Intraventricular; D008297:Male; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology*; D009270:Naloxone / Q000008:administration & dosage; D009638:Norepinephrine / Q000097:blood; D010425:Pentolinium Tartrate / Q000494:pharmacology; D011817:Rabbits; D013564:Sympathetic Nervous System / Q000187:drug effects
D001127:Arginine Vasopressin; D009270:Naloxone; C025043:vasopressin, 1-(1-mercaptocyclohexaneacetic acid)-2-(O- methyl-L-tyrosine)-8-L-arginine-; D009020:Morphine; D010425:Pentolinium Tartrate; D009638:Norepinephrine; D004837:Epinephrine