RT Journal Article
SR Electronic
T1 ACUTE TOLERANCE TO NOREPINEPHRINE IN DOGS
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 336
OP 343
VO 136
IS 3
A1 Marvin E. Rosenthale
A1 Joseph R. DiPalma
YR 1962
UL http://jpet.aspetjournals.org/content/136/3/336.abstract
AB Acute tolerance developed to an infusion of norepinephrine given over a 3-hour period to normal anesthetized dogs. Neither splenectomy nor adrenalectomy altered the development of tolerance. Hemoconcentration, acidosis, decreased blood volume and decreased cardiac output accompanied the development of tolerance. Administration of plasma expanders at the height of tolerance temporarily restored normal sensitivity to norepinephrine but did not affect the acidosis. Adjustment of blood pH to normal with THAM buffer or sodium bicarbonate did not affect tolerance. Experiments designed to demonstrate if neural circulatory adjustments could explain tolerance to norepinephrine were negative. These included the administration of hexamethonium and atropine and decerebration and spinal cord section. No evidence was found for increased removal or destruction of norepinephrine. At the height of tolerance, the norepinephrine levels were very high. Liver monoamine oxidase activity was not enhanced and monoamine oxidase inhibited animals showed the same degree of acute tolerance.