Heart Tissue Concentrations Research Articles

Tissue concentrations and the mortality of d-amphetamine in mice: Changes associated with the use of diethylaminoethyl 2,2-diphenylvalerate · HCl

The concentrations of d-amphetamine produced by doses of 20 to 60 mg/kg were determined in brain, heart, lung, and liver of adult mice and were examined for correlations with mortality. Administration of p-hydroxy-amphetamine with amphetamine did not affect mortality, and the tissue concentrations of this metabolite were not determined. The concentrations of d-amphetamine increased linearly with the dose in brain and lung and nonlinearly in the liver and heart. The concentration in heart tissue varied in a phasic manner, the higher doses (50 and 60 mg/kg) producing lower concentrations than a 40-mg/kg dose. Pretreatment of mice with diethylaminoethyl 2,2-diphenylvalerate · HCl (SKF 525-A) altered tissue concentrations of d-amphetamine only in the liver and the heart. The phasic nature of the d-amphetamine concentrations in heart tissue which was eliminated by SKF 525-A pretreatment corresponded to the elimination of the phasic nature of the lethal dose curve by SKF 525-A.

The effect of 6-aminonicotinamide blockade of the pentose phosphate pathway on catecholamines in the rat adrenal medulla, superior cervical ganglion, hypothalamus and synaptosome fractions.

The effect on tissue catecholamines of blockade of the pentose phosphate pathway with 6-aminonicotinamide (6-AN) was studied in the rat. 6-AN at 35-50 mg kg-1 persistently lowered the adrenaline content in the adrenal gland to less than 10% of control values and caused a 50% loss of noradrenaline, which recovered. When the amine turnover rate was increased by a preceding period of drum stress, 6-AN also consistently depressed noradrenaline in the gland. 6-AN was without significant effect on the noradrenaline concentration in heart tissue, hypothalamus and superior cervical ganglion and did not affect the uptake or release of catecholamines in vitro. The possibility is discussed that 6-AN interferes with the biosynthesis of catecholamines, when it blocks the pentose phosphate pathway, by decreasing the supply of reducing equivalents in the form of NADPH which are necessary for the tetrahydropteridine cofactors of tyrosine hydroxylase.

ALDOSTERONE AND WATER AND SODIUM DISTRIBUTION IN NORMAL AND ADRENALECTOMIZED RATS.

SUMMARY Adrenalectomy in the rat caused an increase of intracellular sodium, both total and relative concentration in heart tissue and a decrease of both in abdominal muscle. These changes were reversed after administration of aldosterone. When aldosterone was given in similar doses to normal animals no changes were observed. It was concluded that an increase in the intracellular sodium concentration of heart and/or other soft tissues, including the adrenals, may stimulate the secretion of aldosterone. A possible regulating system is discussed. It is suggested that total sodium and its intracellular concentration in muscle are influenced by the availability of aldosterone and sodium.

Corticosterone inhibition of pyridine nucleotide oxidase from heart sarcosomes.

IT has recently been found in this laboratory that corticosterone is present in higher concentrations in heart tissue than in plasma1. Since steroid hormones are known to interfere with tissue oxidations, presumably at the level of the flavine enzymes2, the relative abundance of corticosterone in heart tissue suggested a study of the effect of this steroid on heart tissue oxidations in vitro. Reduced diphosphopyridine nucleotide was chosen as substrate in order to get the flavine enzymes involved as directly as possible. The enzyme preparation used in the experiments was made from isolated pig heart sarcosomes. These were ground with alumina oxide, suspended in dilute tris-buffer pH 7.4 and centrifuged for 20 min. at 25,000 g. The opalescent supernatant contained an active reduced diphosphopyridine nucleotide-oxidase3 with a specific activity of about 0.1 µmole reduced diphosphopyridine nucleotide oxidized per min. per mgm. protein at 25° C.