From Macrocirculation to Microcirculation: Benefits of Preterax

Abstract

Maintaining vascular health has become an important target in the management of cardiovascular disease and hypertension-related organ damage. The microvasculature, which is both a target and a determinant of hypertension, contributes to the pathologic changes in the macrocirculation and subsequently to end-organ damage. The major changes in the microcirculation of hypertensive individuals include: (1) an increased wall/lumen ratio of small arteries, (2) a rarefaction of arterioles and capillaries, and (3) an enhanced microvascular permeability. The prevention or regression of hypertension-dependent vascular alterations represents a desirable goal for pharmacologic treatments. Combination treatment with the angiotensin-converting enzyme inhibitor perindopril and the diuretic indapamide (Preterax) has been shown to have positive effects on the microcirculation and macrocirculation and on subsequent cardiovascular disease. In the 1-year pREterax in regression of Arterial Stiffness in a contrOlled double-bliNd (REASON) study, perindopril/indapamide treatment decreased pulse wave velocity and aortic augmentation index, both measures of arterial stiffness and macrovascular health. In addition, data gathered from animal studies show that perindopril/indapamide has a beneficial impact on capillary structure, the endothelium, and angiogenesis. In rat models of renal failure, treatment with perindopril/indapamide prevented glomerular hyalinosis and tubulointerstitial damage, reduced the hypertrophy of superficial glomeruli and the mesangial expansion of deep glomeruli, and positively affected proteinuria and glomerular injury. Together these data suggest that hypertension-related damage to the microvascular and macrovascular system may be manageable through pharmacologic interventions such as combination treatment with perindopril/indapamide.