19-Nor-deoxycorticosterone (19-nor-DOC) is a potent hypertensinogenic mineralocorticoid which may be pathogenic in certain forms of experimental and human hpertension. This study proposes to develop and validate a 19-nor-DOC radioimmunoassay and to apply this RIA to various forms of experimental animal and human hypertension. Since purified 19-nor-DOC is unavailable commercially, 19-nor-DOC will be synthesized by the oxidation of 19-hydroxy-DOC extracted from incubated hamster adrenal glands in vitro. Synthesized 19-nor-DOC will be isolated and purified for immunogen preparation and labelled 1,2 3H-19-nor-DOC for use as a radioligand in the RIA and for constant infusion studies in human subjects. Following validation of the 19-nor-DOC RIA, it will be applied to 3 hypertensive investigations: (1) spontaneously hypertensive rats (SHR), (2) adrenal regeneration hypertension (ARH), and (3) human hypertension. Specifically, SHR and normotensive WKY rats will be studied from 3-8 weeks of age and urinary 19-nor-DOC will be correlated with blood pressure and electrolyte excretion to determine the possible role of 19-nor-DOC as an etiologic factor in this form of hypertension. Similarly, adrenal enucleated Sprague-Dawley rats will have urinary 19-nor-DOC measured during the sodium-retaining phase of ARH. 19-Nor-DOC levels will be correlated with blood pressure and electrolyte balance and compared to intact sham-adrenalectomized controls to determine if 19-nor-DOC is pathogenic in ARH. In human studies, both plasma and urinary 19-nor-DOC excretion and 19-nor-DOC production rates (PR) and clearance rates (CR) will be measured in hypertensive and normotensive subjects during low sodium (10 mEq), high sodium (250 mEq), dexamethasone suppression (2 mg/day), ACTH stimulation (80 U. q. 12), and baseline (sodium 128 mEq) periods. These studies will establish the 19-nor-DOC PR, CR, and plasma levels during various states of adrenocortical stimulation and suppression, and determine whether 19-nor-DOC excess may be associated with hypertensive disease in some individuals. It is possible that abnormal 19-nor-DOC regulation during sodium-surfeit states could produce hypertension in susceptible individuals. The knowledge obtained from these studies should help define the metabolism of 19-nor-DOC and its possible importance in human hypertensive disease.
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| Griffing, G T; Wilson, T E; Melby, J C (1985) Converting-enzyme inhibitor administration lowers urinary free 19-nor-deoxycorticosterone levels. Hypertension 7:178-81 |
| Griffing, G T; McIntosh, T; Berelowitz, B et al. (1985) Plasma beta-endorphin levels in primary aldosteronism. J Clin Endocrinol Metab 60:315-9 |
