The action of chlorothiazide in the perfused cat kidney

Abstract

Crawford & found the prolonged saluretic and diuretic effects which characterize the action of chlorothiazide in man (Laragh, 1958; Bayliss, Marrack, Perkis, Rees & Silva, 1958; and others) and in dogs (Beyer, 1958) were absent both in clinical and experimental diabetes insipidus. The first dose of chlorothiazide caused loss of salt without change in urine volume in these diabetics, so that the osmolarity of the urine rose. Thereafter the saluresis abated but the urine remained concentrated so long as the drug was given, and the daily volume of urine remained about halved. Kennedy & Crawford (1959) attributed this adaptation to the initial saluretic effects of chlorothiazide to change in the effects of the drug on tubular function. Then de los Reyes, Gomez & Bradford (1960) found that chlorothiazide decreased the filtration rate in diabetic patients; this they considered sufficient to explain the decrease in urine volume. They were confirmed in their observation by DAvid, Lazlo & Kovacs (1960), who also showed that the antidiuretic action of chlorothiazide in patients with diabetes insipidus was absent in patients suffering from psychic polydypsia, although both groups of patients lack circulating anti-diuretic hormone (ADH). Davey & Lockett (1960) found differences in the actions of aldosterone monacetate on the isolated cat kidney related to the presence or absence of a circulation through the head during the collection of blood for the perfusion circuit and the making of the heart-lung-kidney preparation. They attributed this difference to the absence of an oxytocin-like substance from blood collected in the absence of a head circulation. We were therefore interested to compare the actions of chlorothiazide on isolated kidneys perfused with these two types of blood, and to discover whether oxytocin modified the effects of chlorothiazide in these preparations. METHODSMale, female or neuter cats were used. Anaesthesia was induced with ether and was maintained by the intravenous injection of 1.0 % chloralose in 0.9 % NaCl, 8-0 ml./kg. The larger cats were used as blood donors. Heparinized blood (heparin 1500 u.f100 ml. blood)

Hormonal actions of the heart and of lungs on the isolated kidney

“…The discovery of the influence of variation in cardiac filling on the function of kidneys perfused from heart-lung circuits does not invalidate our former observations (Davey & Lockett, 1960;de Lima & Lockett, 1961;Lockett & Roberts, 1963;Lockett, 1965Lockett, , 1966Lockett, , 1967a. All these earlier perfusions were made at constant pressure and at constant peripheral resistance: cardiac output and hence cardiac filling must therefore have remained unchanged throughout each experiment.…”

Perfusion of Gat Kidneys from Heart-Lung Circuits.

“…The cat kidney, perfused at constant temperature and pressure from a heart-lung circuit, provides a valuable isolated kidney preparation of high sensitivity to hormones ( 1,4,6,7). The cat kidney, perfused at constant temperature and pressure from a heart-lung circuit, provides a valuable isolated kidney preparation of high sensitivity to hormones ( 1,4,6,7).…”