Enhancement of glucocorticoid and mineralocorticoid receptor density in the microcirculation of the spontaneously hypertensive rat

Objective: Elevated blood pressure and abnormal physiological parameters in the microcirculation of the spontaneously hypertensive rat (SHR) can be normalized by adrenalectomy. Thus glucocorticoids and mineralocorticoids may have major control over blood pressure status and organ injury mechanisms in SHRs. As background, this study was designed to examine the distribution of the glucocorticoid and mineralocorticoid receptors in a microvascular network. Methods: Mature SHR and their normotensive controls, the Wistar-Kyoto (WKY) rat, were studied. An immunohistochemical method was developed that provides a comprehensive display of the receptors in all segments of the mesentery microcirculation and the surrounding tissue parenchyma. Results: All cells in the mesentery exhibit immunolabeling of the glucocorticoid receptor with predominant expression in the nuclei of parenchymal and endothelial cells. The mineralocorticoid receptor is expressed also in most cells of the microcirculation and adjacent parenchymal tissue. Both receptors exhibit the highest levels of immunolabel in the wall of the arterioles and venules, with lower levels in capillaries. Compared with WKY rats, the SHRs exhibit significantly enhanced density of glucocorticoid and mineralocorticoid receptors in endothelial cells of arterioles and venules as well as in parenchymal cells. Conclusions: These results suggest that the enhanced sensitivity of the SHR to glucocorticoids and aldosterone may be in part associated with enhanced glucocorticoid and mineralocorticoid receptor densities in the microcirculation.