The role of corticosteriods in the regulation of vascular tone.

Abstract

Time for primary review 31 days. Disease states resulting from excesses of circulating (adreno)corticosteroids include primary hyperaldosteronism, renal artery stenosis, ACTH-secreting tumors, and administration of glucocorticoids for treatment of other diseases. Hypertension is commonly associated with these diseases. Although renal sodium retention and intravascular volume overload contribute to the attendant hypertension, especially early in the course of the disease, a non-renal mechanism (increase in peripheral vascular resistance) is involved in the development and maintenance of hypertension. The concept of non-renal actions of corticosteroids in the development of hypertension stems from a seminal report in which Langford and Snavely [1]demonstrated that deoxycorticosterone acetate raised blood pressure in dogs and rats devoid of renal mass. In addition, corticosteroids in lesser amounts are essential for the maintenance of peripheral vascular resistance in healthy persons. This review details the proposed mechanisms by which corticosteroids maintain and, in excess, enhance vascular tone. If corticosteroids indeed regulate vascular tone, vascular smooth muscle cells (VSMCs), the vasoactive element of the vasculature, should contain specific receptor molecules for corticosteroids. Classically, corticosteroid receptors are considered to be members of the steroid receptor superfamily of ligand-dependent transcription factors [2]. Radioligand binding studies have defined two distinct cytosolic corticosteroid receptors. Type I (mineralocorticoid) receptors bind with greatest affinity to aldosterone, deoxycorticosterone or corticosterone and with less affinity to the synthetic glucocorticoid dexamethasone. In contrast, type II (glucocorticoid) receptors bind with greatest affinity to dexamethasone and with less affinity to aldosterone, deoxycorticosterone or corticosterone. There is significant base sequence homology between these receptors. Corticosteroid receptors possess highly conserved regions that are necessary for ligand binding, receptor dimerization, nuclear translocation, DNA binding and transactivation (recruiting accessory proteins so that transcription will initiate). The genes for the rat [3, 4]and human [5, 6]mineralocorticoid receptor and the human [7]glucocorticoid receptor … * Tel.: +843-792-4122; fax: +843-792-8399; e-mail: ullianme@musc.edu