Specificity of the Alteration in Aldosterone Biosynthesis in the Spontaneously Hypertensive Rat*

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Abstract
The spontaneously hypertensive rat (SHR) has a decreased aldosterone response to angiotensin II (A II), resulting in a compensatory increase in the activity of the reninangiotensin system. To assess whether this is a selective or generalized defect in hormonal regulation, aldosterone responsiveness to two other secretagogues (ACTH and potassium) and the status of the pituitary-thyroidal and pituitary-adrenal axes were determined in three groups of rats: SHR, normotensive Kyoto-Wistar (WKY), and normotensive Sprague-Dawley rats (SDR). The rats were placed on either a low or a high sodium diet for 10 days, and then blood was obtained for the measurement of plasma aldosterone, corticosterone, A II, ACTH, TSH, T3, sodium, and potassium. Additionally, purified glomerulosa cells were incubated with increasing doses of either ACTH or potassium. No differences between the groups were observed in vivo for any of the parameters measured when the animals were on a high salt diet or for any on the low salt diet, except A II and aldosterone. While all three groups demonstrated an increased plasma aldosterone level with sodium restriction, the SHR had significantly lower levels (378 ± 86 ng/dl) than the SDR (1100 ± 59 ng/dl; P < 0.01) or WKY (707 ± 151 ng/dl; P < 0.03). Similar to in vivo results, baseline aldosterone production by glomerulosa cells in animals on the low salt diet was significantly lower in the SHR than in the normotensive rats (P < 0.001). Yet, there was no significant difference between the SHR and WKY in their ability to respond to either ACTH or potassium. In contrast, the SDR had a slightly greater aldosterone increment in response to potassium than did the other two strains. Since the SHR has a reduced adrenal response to A II, but not to ACTH or potassium, compared to its normotensive genetic control (WKY), we conclude that the defect in aldosterone secretion in these animals is at the A II receptor site and/or at a postreceptor site exclusively involved in mediating A II-induced steroidogenesis.