Circulatory therapeutics: use of antihypertensive agents and their effects on the vasculature

• Antihypertensive agents - Diuretics - β-blockers - Calcium channel blockers - Angiotensin converting enzyme inhibitors - Angiotensin receptor blockers - ACEIs versus ARBs versus CCBs versus diuretics - Direct renin inhibitors - a-adrenergic blockers - Centrally acting agents - Direct vasodilators - Mineralocorticoid receptor blockers - Endothelin receptor antagonists • Effects of antihypertensive treatment on blood vessels - Antihypertensive therapy and large artery stiffness - Antihypertensive therapy and small artery structure - Antihypertensive therapy and small artery function - Effect of antihypertensive treatment on arterioles • Conclusions and future perspectives This review addresses the use of the different antihypertensive agents currently available and some in development, and their effects on the vasculature. The different classes of agents used in the treatment of hypertension, and the results of recent large clinical trials, dosing protocols and adverse effects are first briefly summarized. The consequences on blood vessels of the use of antihypertensive drugs and the differential effects on the biology of large and small arteries resulting in modulation of vascular remodelling and dysfunction in hypertensive patients are then described. Large elastic conduit arteries exhibit outward hypertrophic remodelling and increased stiffness, which contributes to raise systolic blood pressure and afterload on the heart. Small resistance arteries undergo eutrophic or hypertrophic inward remodelling, and impair tissue perfusion. By these mechanisms both large and small arteries may contribute to trigger cardiovascular events. Some antihypertensive agents correct these changes, which could contribute to improved outcome. The mechanisms that at the level of the vascular wall lead to remodelling and can be beneficially affected by antihypertensive agents will also be addressed. These include vasoconstriction, growth and inflammation. The molecular pathways contributing to growth and inflammation will be summarily described. Further identification of these signalling pathways should allow identification of novel targets leading to development of new and improved medications for the treatment of hypertension and cardiovascular disease.