TY - JOUR T1 - THE RELEASE OF NOREPINEPHRINE FROM THE MAMMALIAN HEART BY RESERPINE JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 153 LP - 160 VL - 123 IS - 2 AU - Matti K. Paasonen AU - Otto Krayer Y1 - 1958/06/01 UR - http://jpet.aspetjournals.org/content/123/2/153.abstract N2 - Experiments were conducted in the heart-lung preparation of the dog (HLP), in intact dogs, and in intact rats in order to examine further the effect of reserpine upon the content of norepinephrine (NE) and epinephrine (E) of the heart. The analyses of the catechol amine content of the tissues (right atrium and left ventricle of the dog heart, total heart and total lungs of the rat) were made biologically using the blood pressure of the cat and the rectal cecum of the hen. The heart rate increase in the HLP after reserpine administration is the result of NE release from the heart tissue. In the HLP in a state of myocardial failure there is a concomitant positive inotropic effect. Veratramine antagonizes the reserpine-induced tachycardia but not the improvement of the work capacity of the heart. Administration of reserpine (about 3 mgm./l. of blood) to the HLP leads to a marked decrease of the NE content of the heart after two hours or more; the E content, which normally is 5 per cent that of NE, shows no clear-cut decrease. There is no increase in the NE or E content of the plasma taken from the coronary sinus outflow during the maximal heart rate increase following administration of 3 mgm. reserpine to the HLP. Dogs treated with reserpine (0.5 mgm./kgm. body weight, intraperitoneally) 3 and 2 days prior to removal of the heart for analysis do not have NE in their hearts, the cardiac stores of E, though apparently lower, are not depleted. In the HLP, prepared from dogs pretreated in this manner, reserpine does not increase the heart rate. In the rat heart in situ, reserpine (5 mgm./kgm. body weight, intraperitoneally) causes the disappearance of 90 per cent or more of NE within two hours. Replenishment requires about two weeks. There is no indication of E depletion along with the disappearance of NE. Likewise, in the rat lungs in situ, a depletion of NE, but not of E, follows the administration of reserpine. 5-Hydroxytryptamine, when given to the HLP by continuous infusion at rates between 0.1 and 100 microgm./min. does not increase the heart rate. The contents of NE and E in the hearts of large sized (17 to 26, average 22 kgm.) dogs are significantly lower than those of small sized (8.7 to 13, average 9.8 kgm.) dogs. ER -