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Biomedical subjects

D J Morris

Publications and source records attributed to D J Morris.

At least 199 records · Page 11Linked to original sources
PubMed1983

Antinatriuretic and kaliuretic activities of the reduced derivatives of aldosterone.

The mineralocorticoid activities of the two dihydro- and the four tetrahydroisomers of the ring A-reduced derivatives of aldosterone were tested in adrenalectomized male rats. Potency was assessed by three criteria. Overall mineralocorticoid activity is expressed as the ability to reduce the urinary Na+/K+ ratio; antinatriuretic activity is represented by decreases in urinary Na+/creatinine; kaliuretic activity is shown by increases in K+/creatinine. All measurements were made on urine collected in the period 1-3 h postinjection. Measurements of overall activity indicate that the potency of aldosterone is greater than 5 alpha-dihydroaldosterone (DHA) greater than 3 alpha, 5 alpha-tetrahydroaldosterone (THA) greater than 3 alpha, 5 beta-THA greater than 3 beta, 5 alpha-THA greater than 5 beta-DHA greater than 3 beta, 5 beta-THA. Measurements of individual cation effects indicated that reduced derivatives generally, and the 5 alpha-reduced derivatives in particular, have greater antinatriuretic than kaliuretic activity. For example 5 alpha-DHA possesses between 7% and 17% of the antinatriuretic activity of aldosterone but only 0.7-2.7% of the kaliuretic activity. 5 alpha-DHA and 3 alpha, 5 beta-THA at concentrations of 10(-7)M were also shown to have mineralocorticoid activity in the isolated toad bladder; both caused an increase in the short circuit current across this epithelium although not to the level shown by a similar concentration of aldosterone. 5 beta-DHA appeared to be inactive at this dose.

Adrenalectomy↗
PubMed1982

Aldosterone and its metabolism in spontaneously hypertensive rats (SHR).

The development of hypertension in spontaneously hypertensive rats (SHR) was blocked by adrenalectomy and restored with aldosterone treatment. The blood pressures of normotensive strains of rat were not affected by aldosterone. Infusions of 10 micrograms aldosterone/day into adrenalectomized (ADX)--SHR, Wistar Kyoto (WKY) and Sprague-Dawley (SD) rats completely suppressed plasma renin activity in all strains and lowered plasma potassium levels to below normal in WKY and SD rats; aldosterone treated SHR were normokalemic. In acute studies, SHR responded normally to the antinatriuretic actions of aldosterone but gave a shallower kaliuretic response compared with WKY and SD rats. The urine of ADX-SHR injected with 3H-aldosterone contained a larger proportion of polar neutral metabolites of aldosterone than WKY urine but smaller amounts of acidic and sulfate metabolites. HPLC of the neutral metabolites showed that several polar compounds were present in larger amounts in SHR urine but that unmetabolized aldosterone was less than in WKY urine.

Adrenalectomy↗
PubMed1981

The role of cytochrome P-450 in the synthesis of polar metabolites of aldosterone by microsomes of male rat liver.

Among the tissues of the male rat studied, the largest quantities of the neutral polar metabolites of aldosterone were synthesized by the hepatic microsomal fraction. The polar metabolites of aldosterone were separated by HPLC into six peaks. Three peaks of non-polar (reduced) metabolites were also synthesized. Synthesis of at least four of the neutral polar metabolites was induced by phenobarbital and inhibited by both CO and SKF-525A. The rates of synthesis of these metabolites, which were linear up to 5 minutes, correlated well with the concentration of cytochrome P-450 in the liver microsomes. Addition of aldosterone to the microsomal fraction caused a pronounced type I change in the cytochrome P-450 spectrum. The half maximal spectral change (KS) for aldosterone was calculated to be 8 microM. These experiments indicate that the neutral polar metabolites of aldosterone are produced by cytochrome P-450 dependent hydroxy lations.

Aldosterone↗
PubMed1981

The role of aldosterone in the development of hypertension in spontaneously hypertensive rats.

A continuous sc infusion of aldosterone for 2 weeks (10 micrograms/day) markedly increased the blood pressure of male, adrenalectomized (ADX), spontaneously hypertensive rats (SHR) from 142 to 178 mm Hg, which was similar to the increase seen in a group of sham-operated SHR. The blood pressure in a group of ADX SHR maintained without aldosterone declined from 141 to 119 mm Hg during the 2 weeks after surgery. Wistar Kyoto (WKY) and Sprague-Dawley (SD) rats treated in an identical fashion remained normotensive throughout. Adrenalectomy caused hyperkalemia in all strains of rat. Plasma potassium levels in aldosterone-treated WKY and SD rats were lower than those in sham-operated controls, but were similar to those in corresponding groups of SHR. Acute renal responses of ADX male rats showed that SHR reabsorbed more water and sodium of an injected isotonic saline load than WKY rats and excreted less potassium than either WKY or SD rats. Sensitivity to aldosterone in the three strains of rats was compared using the urinary sodium to creatinine and potassium to creatinine ratios 1-3 h postinjection of aldosterone. Decreases in the urinary ratio of sodium to creatinine in response to various doses of aldosterone (0-1.25 micrograms aldosterone) were similar for the three strains of rat. ADX SHR appeared to be less responsive to the kaliuretic actions of aldosterone than WKY and SD rats. The present studies show that aldosterone is essential to the development of hypertension in SHR. The hypertensinogenic actions of aldosterone in these rats may be related to a blunted kaliuretic response to mineralocorticoids.

Adrenalectomy↗
PubMed1976

The effects of castration and treatment with testosterone on the biliary excretion of (3H)aldosterone in rats.

The rate of excretion of aldosterone radiometabolites into the bile duct cannulation, and the intravenous injection of (3H)aldosterone, was demonstrated to be markedly increased in male rats following castration. In 1 h, 72% of the injected 3H-radioactivity was excreted in the bile of castrated male rats compared with 26% in the intact male control rats. Castration of the males led to the increased biliary excretion of aldosterone metabolites and the elimination of the sex-dependence of this process in rats. The ovariectomy of female rats did not substantially increase the rate of excretion of aldosterone metabolites via the bile. Castrated male rats treated with testosterone excreted aldosterone metabolites into the bile at a slower rate. A similar treatment of ovariectomized female rats with testosterone also significantly slowed the rate of biliary excretion of the aldosterone metabolites. These findings suggest that the presence of androgens plays an important role in regulating the routes of hepatic metabolism of aldosterone and the rates of clearance of aldosterone and its metabolites from the plasma into the bile of rats.

Aldosterone↗