Arterial steroid receptors and their putative role in the mechanism of hypertension.

Data from clinical and experimental studies indicate that mechanism(s) for action of mineralocorticoids, other than renal, must be involved in the overall effect of mineralocorticoids on circulation--increased peripheral resistance and hypertension. We have postulated existence of such a mechanism in the arterial wall and have looked for the evidence for its presence. We have found high affinity, specific binders for mineralocorticoids, and glucocorticoids, with characteristics of steroid receptors, in the cytosol of rabbit aorta and femoral and carotid arteries. These binders possess physico-chemical properties of steroid receptors and, moreover, they translocate to cell nuclei (as steroid-receptor complexes) and bind to relatively specific "acceptor-sites" on nuclear chromatin. This provides evidence for the existence in the arterial wall of a molecular mechanism for a direct in situ action of mineralocorticoids and glucocorticoids. The mineralocorticoid receptors are not present in veins. We have also found that chronically elevated levels of 11-desoxycorticosterone (DOC) result in a marked increase in permeability of arterial smooth muscle cell membrane to sodium ions; this is in accord with findings of other investigators in the rat. This change presumably leads, through a chain of biochemical events, to increased arterial and arteriolar smooth muscle contractility, increased peripheral resistance and hypertension. Study is in progress to determine whether the effect of DOC on arterial smooth muscle cell-membrane permeability to electrolytes is elicited through the receptor-mediated mechanism for the in situ action of mineralocorticoids in the arterial wall. It is postulated that this mechanism is primarily responsible for "mineralocorticoid hypertension", but may well be instrumental also in pathogeneses of various other forms of hypertension, including "essential".