GPCR models of pain in cardiovascular diseases: Contributions of kinins and endothelins

Antagonists targeting the G-protein coupled receptors for endothelin-1 (ET-1) or bradykinin (BK) are clinically indicated to alleviate morbidity related to primary pulmonary hypertension and digital ulcers associated with Raynaud's syndrome or non-allergic angioedema, respectively.Despite the extensively documented functional cross talks between ET-1 and BK in cardiovascular diseases, none of the currently used antagonists for the two peptides target cardiovascular related pain perception as a primary endpoint.This review highlights the role of both peptides as biomarkers and as modulators of nociceptive responses in specific cardiac and vascular diseases.