Antihypertensive Properties of Angiotensin-Converting Enzyme Inhibitors (ACEI) Independent of the Renin-Angiotensin System

Therezinha      Bandiera Paiva; Jamille      Cristina Rocco Bravo; Nelson      Carvalho Farias; Teresa      Feres

Abstract

Angiotensin converting enzyme inhibitors (ACEi) lead to inhibition of angiotensin II formation and bradykinin inactivation. However, ACEi also have antihypertensive activity that is independent of the renin-angiotensin system. For example, the enhanced peripheral resistance due to smooth muscle cell hypertrophy and hyperplasia (related to lower apoptosis) increases vascular tonus in established hypertension. ACEi treatment restores susceptibility to apoptosis in these cells through stimulation of the Bax protein. Also, an altered function of the Na+/K+ ATPase leads to elevated levels of intracellular sodium concentration, and depolarization of smooth muscle membranes increasing their excitability. ACEi treatment normalizes this pump function, and the arterial tonus by release of endothelial nitric oxide and prostacyclin. Endothelium- dependent hyperpolarization (to acetylcholine) in mesenteric arteries mediated by release of the endotheliumderived hyperpolarizing factor, is impaired in hypertensive humans and animals. In this instance, ACEi restored this impaired response, since this treatment causes vascular remodeling in resistance SHR arteries through induction of apoptosis of vascular smooth muscle cells reducing the subendothelial thickening, which improves the EDHF circulation. The purpose of this review is to analyze the performance of ACEi in normalizing the vascular tonus during the hypertensive state, which may render new perspectives in basic and clinical research for the next years.

Keywords: Angiotensin-converting enzyme inhibitors, hypertension, endothelial dysfunction

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