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Role of Endothelin-2 on the Cardiovascular System
Endothelin-2 (ET-2), like endothelin-1 (ET-1), has a role in modulating vascular tone. This can have implications for blood pressure control. A specific EDN2 gene polymorphism has been correlated with essential hypertension and alternative studies have shown associations between certain rare ET-2 polymorphisms and lower diastolic blood pressures. The ET-2 gene has been shown to co-segregate with blood pressure in rodent studies; a potential reason for the link.

However, as transgenic rats expressing the human ET-2 gene under the control of the human endothelin promotor are normotensive (blood pressure in normal range), despite these studies suggesting that overexpression of ET-2 results in glomerulosclerosis. This suggests that further investigation into the role of ET-2 in blood pressure is warranted.

As a strong positive inotrope, endothelin-2 has an impact on the human myocardium and for this reason, endothelin-2 antagonists have been shown to improve exercise tolerance and inhibit clinical deterioration in pulmonary hypertension. ET-2 demonstrates a positive chronotropic and proarrhythmic effects. A study showed a significant association of a specific polymorphism of the EDN2 gene with increased incidence of atrial fibrillation in patients with hypertrophic cardiomyopathy. Overall, the evidence suggests that ET-2 could modulate vascular tone, tissue morphology and remodelling.