ABSTRACT
The high secretion rate of 18-hydroxydeoxycorticosterone in hypertensives and the steroids implication as a mineralocorticoid has led to the synthesis of potential di-, tetra-, and hexahydro metabolites of it and 18-hydroxy-progesterone. These potential metabolites have been synthesized by reduction of the double bond and the 3- and 20-ketones, singly or in combination. They have been evaluated for pro- and antimineralocorticoid activity and their affinity for the renal aldosterone receptor. All except one of the potential metabolites either lack or have reduced mineralocorticoid activity and aldosterone receptor binding affinity. The exception is the 3-ketopregn-4-ene-18,20-diol which has high receptor affinity but functions as an aldosterone antagonist.
Subject(s)
18-Hydroxydesoxycorticosterone/metabolism , Desoxycorticosterone/analogs & derivatives , Hydroxyprogesterones/metabolism , Animals , Hypertension/metabolism , Kidney/metabolism , Male , Rats , Receptors, Glucocorticoid/metabolism , Receptors, MineralocorticoidABSTRACT
The beneficial antiulcer actions of carbenoxolone may possibly be due to an aldosterone-like component on the gastric mucosa. This suggests that aldosterone and possibly other corticoids may have antiulcer actions. The potential gastric antisecretory and antiulcer actions of aldosterone (ALDO) and desoxycorticosterone acetate (DOCA) were studied in the rat in comparison to the reference standard carbenoxolone. Stress ulcers were induced in fasted rats by the the forced exertion technique. Gastric secretion was evaluated in the five-hour pyloric ligated Shay rat model. The renal mineralocorticoid actions of these drugs were also studied in the adrenalectomized rat. Intragastric administration of carbenoxolone and DOCA, but not ALDO, significantly inhibited gastric ulcer formation in rats. Carbenoxolone given subcutaneously (s.c.) did not inhibit ulcer formation. ALDO exhibited antiulcer actions only when multiple s.c. injections were made. The antiulcer actions of DOCA and ALDO are not mediated via an inhibitory effect on gastric secretion. At all doses tested DOCA and ALDO showed significant renal effect, while carbenoxolone exhibited this effect only at the highest tested dose. These results suggest that the beneficial antiulcerogenic action of carbenoxolone is due to a direct effect on gastric mucosa and is not related to an aldosterone-like component.
Subject(s)
Aldosterone/pharmacology , Anti-Ulcer Agents , Carbenoxolone/pharmacology , Desoxycorticosterone/pharmacology , Gastric Mucosa/drug effects , Glycyrrhetinic Acid/analogs & derivatives , Animals , Gastric Mucosa/metabolism , Male , Mineralocorticoids/blood , Rats , Stomach Ulcer/prevention & control , Stress, Physiological/complicationsABSTRACT
In unanesthetized water-loaded rats, intracerebroventricular (IVT) angiotensin II (AII) injections produce centrally mediated pressor effects and antidiuresis. Experiments were performed to evaluate the role of antidiuretic hormone (ADH) release versus neurogenic mechanisms in the antidiuretic responses to central AII median eminence lesions used to block ADH release abolish antidiuretic effects but only attenuated pressor responses to IVT AII infusions. Pretreatment with an intravenous infusion of ADH antibody had a similar effect. Central administration of AII in water and saline-loaded rats produced no change in effective renal plasma flow or glomerular filtration rate, Natriuretic and kaliuretic responses to IVT AII injections were similar to those observed to intravenous ADH infusions. These data are consistent with the suggestion that antidiuresis and osmotic excretion observed after IVT AII injections in the rats are the result of ADH release, and that neurogenic mechanisms play a major role in the blood pressure but not in the antidiuretic responses.
Subject(s)
Angiotensin II/pharmacology , Hypothalamo-Hypophyseal System/drug effects , Kidney/drug effects , Median Eminence/drug effects , Vasopressins/metabolism , Water-Electrolyte Balance/drug effects , Angiotensin II/administration & dosage , Animals , Blood Pressure/drug effects , Diuresis/drug effects , Glomerular Filtration Rate/drug effects , Injections, Intraventricular , Kidney/blood supply , Natriuresis/drug effects , RatsSubject(s)
Angiotensin II/pharmacology , Vasopressins/metabolism , Animals , Blood Pressure/drug effects , Carbachol/pharmacology , Dose-Response Relationship, Drug , Heart Rate/drug effects , Hypophysectomy , Injections, Intravenous , Injections, Intraventricular , Male , Rats , Reaction Time/drug effects , Sympathectomy , Vasopressins/administration & dosage , Vasopressins/pharmacologyABSTRACT
A semiautomated method for microanalysis of dextran with anthrone reagent has been developed. The method utilizes the Technicon inulin manifold and other standard AutoAnalyzer equipment. Since the anthrone method is sensitive to plasma glucose, a glocuse oxidase method which eliminates glucose in samples to be analyzed for dextran has also been developed. When solutions containing 50 mg. per 100 ml. of dextran were compared to solutions containing 50 mg. per 100 ml. of dextran plus up to 200 mg. per 100 ml. glucose, no significant difference was observed. The coefficient of the anthrone-glucose oxidase method is 0.039, which is within the error of the AutoAnalyzer itself.
