Endothelin-1 also referred as preproendothelin-1, is encoded by EDN1 gene. The gene is processed proteolytically and leads to release of endothelin-1 peptide. This peptide hormone is a potent vasoconstrictor produced by vascular endothelial cells. These properties of endothelin-1 has made it known for its major role in hypertension.

Research has shown various complex roles played by endothelin-1 in reproductive, pulmonary, cardiovascular, renal and neural physiology. This requires a tight regulation of endothelin-1 production. The rate of transcription of the gene is one mechanism to regulate the expression of endothelin-1. Studies have shown various crucial transcriptions factors in different cell types.

Ability of endothelin-1 gene to respond to different stimuli is important for maintaining the quantitative endothelin-1 expression in the body. Alterations in expression of edn1 gene have been reported to be associated with human diseases like proteinuria, cancer, atherosclerosis, asthma and various other diseases. This makes it clear that edn 1 transcription and expression of endothelin-1 is very important in maintaining the physiology and pharmacology of humans.

Few studies have explored how hypercalcemia stimulates production of endothelin-1 in kidney and increase in transcription of edn 1 gene through activation by CaR. The expression of endothelin-1 was analysed in kidney of rats with hypercalcemia. The study showed increased concentration of endothelin-1 in the cortex of kidney and not in the medulla during hypercalcemia. This was entirely opposite to the concentrations of endothelin-1 observed in normal conditions. It was understood that polyuria caused during hypercalcemia leads to dehydration. This may result in increased endothelin-1 expression. 

Distribution pattern of CaR expression also shows a contribution towards the specific induction of endothelin-1 in the kidney cortex. Thus, these studies demonstrate various stimuli and hormones that lead to increased expression of endothelin-1.