[Mechanism of primary hypertension]

We review various theories of the pathogenetic mechanisms of steroid-induced and essential hypertension. We investigated the possibility that a pathogenetic mechanism leading to glucocorticoid (GC)-induced hypertension or to mineralocorticoid (MC)-induced hypertension, or both, may be of critical importance in primary hypertension. We studied plasma levels of corticosterone (BK) and aldosterone (Aldo), and their concentrations in arterial and renal tissues of spontaneously hypertensive rats (SHR), a model of primary hypertension, and in the antecedent strain WKY rats as a normotensive control. Plasma levels of BK and Aldo were found to be normal and identical in SHRs and WKYs. Tissue (intracellular) levels of BK were more than double in SHRs than in WKYs. Subsequently we examined the activity of 11 beta-hydroxy steroid dehydrogenase (11-HSD) in both aortic and renal tissues of SHRs and WKYs. 11-HSD converts BK to the corresponding 11-keto compound, 11-dehydro-corticosterone (cpd.AK), which is inactive, in view of its inability to bind to the MC receptors (and also to the GC receptors). BK, the main glucocorticoid in the rat, as well as cortisol, have high affinity for the MC-receptor (MR). Normally BK or cortisol are present in 10(2)-10(3) times greater concentrations than Aldo in tissues possessing MR. The enzyme 11-HSD deactivates BK (or cortisol), thus protecting MC-receptors in the MC target tissues from being activated by GC. When we examined arterial and renal tissue activities of 11-HSD in SHRs, the activity of 11-HSD was only one-third that found in the WKY rats. This explained higher levels of BK in the tissues of SHR, and suggested that decreased activity of 11-HSD is a pathogenetic factor for hypertension in SHRs. Thus, in a model of primary hypertension such as SHR, decreased activity of 11-HSD in the target tissues of MC appears to lead to glucocorticoid-induced mineralocorticoid hypertension.