Structural and functional changes of the microcirculation in hypertension: Influence of pharmacological therapy

The increased peripheral resistance in hypertension results from arteriolar vasoconstriction, increased media-to-lumen (M/L) ratio of small resistance arteries, and rarefaction (reduction in density) of microvessels. Numerous neurohumoral and hormonal factors are involved in causing structural and functional changes in the microcirculation in hypertension, including the renin-angiotensin-aldosterone system, remodelling of the extracellular matrix, increased growth of the smooth muscle cells of the media, and elevated collagen and fibronectin deposition. Although a wide variety of pharmacological agents can decrease blood pressure (BP) in hypertension, they vary in their ability to reverse structural and functional changes in the microcirculation. ACE inhibitors have consistently been shown to regress microvascular changes but findings with calcium antagonists have been variable and beta-adrenoceptor blockers appear to have no effect. In studies with ACE inhibitors, improvements in the M/L ratio and endothelial function of small resistance arteries have been recorded in both animal models of hypertension and human subcutaneous arteries obtained by biopsy of gluteal tissue from patients with essential hypertension. Recent studies with the very low-dose combination of perindopril and indapamide have indicated that these agents act synergistically to restore normal microvascularisation and reverse capillary rarefaction in the coronary circulation of hypertensive rats, and normalise coronary blood flow reserve in humans with hypertension. The additional benefit accruing from regression of structural and functional abnormalities in critical vascular beds such as coronary or renal circulations of patients with chronic hypertension may well become an important factor in selection of antihypertensive therapy, as complications such as ischaemic episodes and other target organ damage may be prevented and the BP-lowering effect of treatment may be extended such that it continues even after withdrawal. However, whether improvements in microcirculatory structure and function will be associated with improved morbidity and mortality outcomes in patients with chronic hypertension has yet to be firmly established.