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(Hypertension. 2008;52:1019.)
© 2008 American Heart Association, Inc.

Editorial Commentaries

Direct Renin Inhibition

Another Weapon to Modulate the Renin-Angiotensin System in Postinfarction Remodeling?

Stefano Perlini; Francesco Salinaro; Maria Luisa Fonte

From the Clinica Medica II (S.P., F.S., M.L.F.), Dipartimento di Medicina Interna e Terapia Medica, Fondazione IRCCS Policlinico "San Matteo," Università di Pavia, Pavia, Italy; and the Centro Interuniversitario di Fisiologia Clinica ed Ipertensione (S.P.), Pavia, Monza and Milan, Italy.

Correspondence to Stefano Perlini, Clinica Medica II, Fondazione IRCCS Policlinico "San Matteo," Università di Pavia, P.le Golgi 2, 27100 Pavia, Italy. E-mail stefano.perlini@unipv.it

An extract of the first 250 words of the full text is provided, because this article has no abstract.

The process of cardiac healing and recovery after an acute myocardial infarction encompasses profound changes in the necrotic area ("infarct zone"), in the neighboring ischemic zone ("area at risk"), and in the nonischemic myocardium ("nonischemic region"). Patient’s prognosis ultimately depends on the functional, biochemical, electric, and structural changes taking place in these 3 different areas as a consequence of the acute ischemic event. These extracellular, cellular, and subcellular events are globally referred to as "postinfarction remodeling," and therapeutic interventions able to slow or reverse its progression have a favorable impact on patient prognosis.¹

A pivotal role in these processes is played by the renin-angiotensin-aldosterone system (RAAS) that is undoubtedly hyperactivated after myocardial infarction, together with other neural and endocrine systems. Locally synthesized angiotensin II has been suggested to act as an autocrine, paracrine, and intracrine modulator of cardiac function.² Notably, the major components of the RAAS components have been shown in cardiac tissue, and extracardiac renin uptake is associated with local release by myocardial mast cells.³

Angiotensin II intracellular signal transduction involves the phosphorylation of several proteins, such as membrane transporters and selective ion channels, structural and contractile proteins, and enzymes that regulate metabolism, protein synthesis, and gene expression. These multiple actions are mediated via complex intracellular signaling pathways, including stimulation of the phospholipase C-inositol 1,4,5-trisphosphate-1,2-diacylglycerol cascade, mitogen-activated protein kinases, tyrosine kinases, RhoA/Rho kinase, and reactive oxygen species generation through vascular NADPH oxidase activation. Beyond directly affecting vasomotor tone, angiotensin II potentiates the effects of several vasoconstrictor hormones, facilitates the . . . [Full Text of this Article]

Related Article:

Renin Inhibition Improves Cardiac Function and Remodeling After Myocardial Infarction Independent of Blood Pressure

Dirk Westermann, Alexander Riad, Olga Lettau, Anton Roks, Konstantinos Savvatis, Peter Moritz Becher, Felicitas Escher, A.H. Jan Danser, Heinz-Peter Schultheiss, and Carsten Tschöpe
Hypertension 2008 52: 1068-1075. [Abstract] [Full Text] [PDF]