Our objective is to study low renin hypertension of childhood. 1. To study the role of known hormones in low renin hypertension. a. Is aldosterone the pressor steroid in dexamethasone-suppressible hyperaldosteronism (DSH). Is DOC the pressor steroid in 11Beta-hydroxylase and 17-hydroxylase deficiency. We shall establish whether the hormones measured in excess in low renin hypertensive syndromes are indeed the pressor steroids raising blood pressure. We shall measure the effect of administering the excessive steroid on blood pressure during dexamethasone suppression when blood pressure is normal. Should the results indicate that aldosterone or DOC do not raise blood pressure, we shall look for a yet unidentified steroid capable of raising blood pressure. b. Do androgens play a role in the rise of blood pressure in DSH. Evidence in both animal and human models have suggested that gonadal androgens may exert control over blood pressure. We have observed elevated serum androgen levels in prepuberty in children with DSH. Our hypothesis is that this precocious rise of androgens contributers to elevation of blood pressure. We propose to measure the effect of administration of the androgen, DHEA-S, on blood pressure in the dexamethasone suppressed state when androgens and blood pressure are reduced to normal. 2. To study the role of yet unidentified hormones in low renin hypertension of childhood. The proposed research is directed towards characterizing and quantifying these unknown steroids in DSH and in other forms of low renin hypertension. 3. To use the rat renal slice radioreceptor assay to search for unidentified steroids with mineralocorticoid-binding activity in children with low renin hypertension. We shall study patients with low renin hypertension for total mineralocorticoid-binding activity to screen for yet unidentified receptor-binding mineralocorticoids. 4. To study the role of the mineralocorticoid receptor in vivo in children with low renin hypertension. We shall use the colonic potential difference (PD) as a measure of the activity of the mineralocorticoid receptor in vivo in children. We shall correlate this measurement with the circulating level of mineralocorticoids. When there is a disparity in the concentration of mineralocorticoids and the PD, we shall investigate the cause of the disparity. In order to accomplish this aim, we must establish reference data for PD in normal infants and children, and in children with hypo and hyper-mineralocorticoid states. Using these reference data, we will use colonic PD measurements to study patients with low renin hypertension in which the mechanism of the excess mineralocorticoid activity remains to be explained.
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