The Use of Histamine as a Standard Test for Diminished Resistance in Suprarenalectomized Rats

Abstract

The resistance of suprarenalectomlzed animals to a number of nonspecific poisons is markedly reduced, as has been shown by several independent workers (1-6). These observers employing such poisons as cobra venom, curare, morphine, diphtheria toxin and typhoid vaccine were able to demonstrate a striking difference in resistance between normal and suprarenalectomized rats. In comparing the results obtained in different laboratories with the same poison, considerable differences in the lethal dose appeared to exist. With some of the poisons, as for example, typhoid vaccine, it seemed likely that the difference could be explained by a lack of uniformity of the preparation. Inasmuch as this test may have considerable value in future experimental work, it seemed advisable to secure additional data concerning certain of these poisons in order to find a stable substance having a relatively constant ratio between the lethal dose for suprarenalectomized rats and that for normal rats. This ratio should be at least 1:20. If such a substance could be found, the test might be standardized. In our attempts to standardize this test, we have used, up to the present time, typhoid vaccine, chloral hydrate, sodium cyanide and histamine, and the results obtained may be summarized as follows:Typhoid Vaccine.--Marine and his coworkers (4) have shown that 75 per cent of rats are killed by 0.25 cc. of a standard typhoid vaccine within 8 days after suprarenalectomy. In a recent paper we showed (6) that suprareualectomized rats surviving in good condition are killed by typhoid vaccine in doses of 0.4-1 cc. at the height of susceptibility (5-7 days). On repeating these experiments, it was noted 5o3 on

The Effect of Bilateral Suprarenalectomy in Adult Albino Rats on the Natural and Acquired Resistance to Bartonella Muris Anemia

“…By work in this laboratory and that of other investigators, it has been shown that the suprarenal glands are essential in the mechanism of natural resistance (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12). In the case of suprarenalectomized rats, this resistance can be raised almost to normal by injection of the hormone of the suprarenal cortex (13)(14)(15).…”

Immunological Studies in Relation to the Suprarenal Gland

“…The depression of antibody formation during the 1st week coincides with the marked depression in resistance of suprarenalectomized rats noted by numerous observers (2,(5)(6)(7). It was found by one of us (8,9) that the height of susceptibility of rats to typhoid and to histamine poisoning is reached during the period from 5 to 7 days after bilateral suprarenalectomy.…”

Phenylbutazone and Histamine Formation in Rat Glandular Stomach: Its Relationship to Gastric Ulceration

“…The sensitivity of adrenalectomized rats to phenylbutazone was increased by fasting for 24 hr before administration of the drug; this produced a further increase in the ulceration index and a decrease in the survival time after injection. An increased sensitivity of adrenalectomized rats to histamine is well known (Voegtlin & Dyer, 1924;Crivellari, 1927;Marmorston-Gottesman & Gottesman, 1928;Scott, 1928;Perla & Marmorston-Gottesman, 1931;Noble & Collip, 1941). There is some evidence that the increased histamine formation in situ (Schayer, 1962b) and the diminished resistance of the atrophied gastric mucosa in the adrenalectomized rats (Shay, Bralow, Kovarov & Kessler, 1962;Kyle, Clarke, Ward, Adesola & Welbourn, 1963) are responsible for the development of ulceration and death in these animals.…”