Raines and Niner, Neuropharmacology (1975),2032 demonstrated in cats that PHT (10-20 mg/kg) reduced systolic and diastolic blood pressure and heart rate, which had been elevated by carotid occlusion.

2032. Raines, A. and Niner, J. M., Blockade of a sympathetic nervous system reflex by diphenylhydantoin, Neuropharmacology, 14: 61-66, 1975.

Lew, Proceedings of the Society of Experimental Biology and Medicine (1975),1282 found that PHT increased the concentration of norepinephrine in the hypothalamus, cerebellum and brainstem in a strain of naturally hypertensive rats. The author notes that a deficiency in norepinephrine in the hypothalamus has been reported in hypertension, and that certain treatments effective in reducing high blood pressure produce an increase of norepinephrine in the hypothalamus.

1282. Lew, G. M., Increased hypothalamic norepinephrine in genetically hypertensive rats following administration of diphenylhydantoin, Proc. Soc. Exp. Biol. Med., 148: 30-32, 1975.

Dadkar, Gupte and Dohadwalla, Medical Biology (1979),1789 studied the effect of PHT on spontaneously hypertensive rats which exhibit many features similar to human essential hypertension. PHT (5-20 mg/kg), orally for five days, elicited a dose-dependent fall in elevated systolic blood pressure, and increased nor-epinephrine concentration in the hypothalamus. PHT did not lower blood pressure in a group of rats with normal blood pressure.

1789. Dadkar, M. K., Gupte, R. D. and Dohadwalia, A. M., Effect of diphenylhydantoin on blood pressure of spontaneously hypertensive rats, Med. Biol., 57: 398-401, 1979.

See also Refs. 414, 1480, 1717, 1797, 1892, 2090, 2316, 2668.

414. Editor, Hypertension in a young man, JAMA, 143: 939, 1954.
1480. Rose, L. I., Williams, G. H., Jagger, P. I., Lauler, D. P., and Thorn, G. W., The paradoxical dexamethasone response phenomenon, Metabolism, 18: 369-375, 1969.
1717. Aldrete, J. A. and Franatovic, Y., Postponement of operations-its prevention in patients found to be mildly hypertensive, Arch. Surg., II 5: 1204-6, 1980.
1797. de la Torre, R., Murgia-Suarez, J. J. and Aldrete, J. A., Comparison of phenytoin and conventional drug therapy in the treatment of mild hypertension, Clin. Ther., 3(4): 117-24, 1980.
1892. Helfant, R. H., Effectiveness of diphenylhydantoin as an antihypertensive, Personal Communication, 1975.
2090. Starkova, N. T., Marova, E. I., Lemesheva, S. N., Goncharova, V. N., Atamanova, T. M. and Sedykh, L. P., The effect of diphenin on functional condition of the adrenal cortex in patients with Itsenko-Cushing disease, Problemy Endokrinologii, 18: 35-8, Nov/Dec, 1972.
2168. Delini-Stula, A., Radeke, E., Schlicht, G. and Hedwall, P.R., Detection of CNS-depressant properties of antihypertensives: validity of various methods in rodents and estimation of therapeutic margin in hypertensive rats, Pharmac. Ther., 5: 43144, 1979.
2316. Beebtereva, N. P., Nikitina, L. I., Iliuchina, V. A., Dambinova, S. A., Denisova, V. V., Dilantin: clinical and scientific experience of application, Eur. J. Clin. Invest., 14: 36, 1984.
2668. Kotovskaya, E. S., Erina, E. V., Experiment in the use of neurotropic preparations (diphenylhydantoin and pyrroxan) for the purpose of the crisis-preventive treatment of hypertensive patients, Biull, Vsesoiuznogo Kardiol. Nauchn. Tsentra AMN SSSR, 5(l): 75-9, 1982.