Adrenal endothelin-1 levels are not associated with aldosterone secretion in primary aldosteronism

Background. Endothelin-1 (ET-1) may function as an aldosterone secretagogue and, in turn, aldosterone can up-regulate ET-1 expression. Hence, the existence of a feedforward loop involving ETs and aldosterone has been speculated in primary aldosteronism (PA). In the present study, we sought to examine ET-1 secretion from the adrenal glands in patients with PA. Design. We determined ET-1 levels in blood samples obtained during adrenal venous sampling of patients affected by PA (n=17). Further, we examined the mRNA expression of the ET system in tissue samples from aldosterone-producing adenomas (APAs, n=9) and control normal adrenals (n=3). Methods. Blood ET-1 levels were determined by radioimmunoassay. Tissue mRNA expression of the ET system was assayed with Affymetrix microarrays. Results. ET-1 levels did not differ between inferior vena cava and adrenal vein blood in both bilateral adrenal hyperplasia and APA patients. Moreover, cortisol-normalized ET-1 levels did not show lateralized adrenal ET-1 secretion in APAs. Through gene expression profiling with microarray performed in a distinct set of APA individuals (n=9), we confirmed the adrenal expression of a complete ET system, but we did not detect a significant up-regulation of ET components within the APA tissue compared to normal adrenals. Conclusions. The present data argue against the hypothesis of increased ET-1 secretion from APAs and do not support a general role for adrenal ET-1 in the vascular pathophysiology of PA.