Zaher Armaly1, Suheir Assady, Zaid Abassi. 1. aDepartment of Nephrology, EMMS Nazareth - The Nazareth Hospital, Nazareth, Galilee Medical School-Bar Ilan University, Zafed bDepartment of Nephrology cResearch Unit, Rambam Healthcare Campus dDepartment of Physiology, Rappaport Faculty of Medicine, Technion, Israel Institute of Technology, Haifa, Israel *Zaher Armaly and Suheir Assady contributed equally to the writing of this article.
Abstract
PURPOSE OF REVIEW: Natriuretic peptides play a key role in regulation of blood pressure and volume homeostasis due to their natriuretic/diuretic and vasodilatory actions. The natriuretic and diuretic responses to natriuretic peptides are markedly attenuated in edematous disease states. Our goal is to review the mechanisms underlying this phenomenon, with special emphasis on the role of corin in salt retention and edema formation in heart failure and nephrotic syndrome, and pathogenesis of hypertension. RECENT FINDINGS: Although three decades have passed since the discovery of atrial natriuretic peptide (ANP), major advances in understanding the physiological and pathophysiological role of the natriuretic peptide family in the regulation of sodium (Na) and water balance are still emerging. As well as ANP, the natriuretic peptide family contains at least two other members: brain natriuretic peptide (BNP) and C-type natriuretic peptide (CNP). Although encoded by different genes, these natriuretic peptides share a high similarity in their chemical structure and biosynthesis pathway. ANP and BNP are produced from proANP and proBNP, respectively, which are converted into the active forms mainly by corin. The latter is a transmembrane serine protease localized to the heart, and to a lesser extent to the kidneys. Recent studies have demonstrated that perturbations in corin activity lead to elevation of the prohormones at the expense of the mature forms, thereby causing the development of salt-sensitive hypertension, preeclampsia, cardiac hypertrophy, and Na and water retention. SUMMARY: Natriuretic peptides are an important endocrine system in the regulation of body fluid balance and blood pressure. Corin mediates an essential step in the cascade of natriuretic peptide biosynthesis and eventually their action. Thus, it is postulated that aberrations in the normal activity of corin may contribute to cardiovascular and renal diseases.
PURPOSE OF REVIEW: Natriuretic peptides play a key role in regulation of blood pressure and volume homeostasis due to their natriuretic/diuretic and vasodilatory actions. The natriuretic and diuretic responses to natriuretic peptides are markedly attenuated in edematous disease states. Our goal is to review the mechanisms underlying this phenomenon, with special emphasis on the role of corin in salt retention and edema formation in heart failure and nephrotic syndrome, and pathogenesis of hypertension. RECENT FINDINGS: Although three decades have passed since the discovery of atrial natriuretic peptide (ANP), major advances in understanding the physiological and pathophysiological role of the natriuretic peptide family in the regulation of sodium (Na) and water balance are still emerging. As well as ANP, the natriuretic peptide family contains at least two other members: brain natriuretic peptide (BNP) and C-type natriuretic peptide (CNP). Although encoded by different genes, these natriuretic peptides share a high similarity in their chemical structure and biosynthesis pathway. ANP and BNP are produced from proANP and proBNP, respectively, which are converted into the active forms mainly by corin. The latter is a transmembrane serine protease localized to the heart, and to a lesser extent to the kidneys. Recent studies have demonstrated that perturbations in corin activity lead to elevation of the prohormones at the expense of the mature forms, thereby causing the development of salt-sensitive hypertension, preeclampsia, cardiac hypertrophy, and Na and water retention. SUMMARY: Natriuretic peptides are an important endocrine system in the regulation of body fluid balance and blood pressure. Corin mediates an essential step in the cascade of natriuretic peptide biosynthesis and eventually their action. Thus, it is postulated that aberrations in the normal activity of corin may contribute to cardiovascular and renal diseases.
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