Endothelin regulation of adrenal function

1. The goal of the present review is to recount the evidence that endotheli n (ET) has a significant influence on the peripheral sympathetic nervous sy stem by regulating the function of the adrenal medulla. 2. The presence of an active ET system in the adrenal medulla has been clea rly demonstrated. Endothelin protein, mRNA, binding sites and ET-converting enzyme have been identified in adrenal tissue and medullary chromaffin cel ls, suggesting that this peptide may contribute to the regulation of adrena l medullary function. 3. Studies investigating the function of ET in the adrenal gland have demon strated that ET has a stimulatory effect on the adrenal medulla, Endothelin elicits an increase in catecholamine release from perfused intact adrenal glands as well as from cultured chromaffin cells. This effect has been show n to be mediated by ETA and ETB receptors, 4. The mechanism by which ET causes an increase in catecholamine release fr om the adrenal medulla appears to be independent of cholinergic activation of chromaffin cells, Endothelin has been shown to act directly at chromaffi n cells to increase intracellular calcium, which results in catecholamine r elease. 5. Endothelin can indirectly affect catecholamine release by its effect on adrenal blood flow. Studies indicate that ET has both vasoconstrictor and v asodilator effects in the adrenal gland, which suggests a role for ET in th e regulation of adrenal blood flow. Endothelin has also been proposed to pa rticipate in the selective contraction of the adrenomedullary veins, which enhances the discharge of catecholamines from the adrenal gland during acti vation.