Pharmacological Modulations of the Renin-Angiotensin-Aldosterone System in Human Congestive Heart Failure: Effects on Peripheral Vascular Endothelial Function

Elevated peripheral vascular tone has been proposed as one of the detrimental factors causing increased cardiac after load and reduced exercise capacity in patients with congestive heart failure (CHF). A number of studies have shown impaired endothelium-dependent vasodilation in limb resistance and conduit vessels in CHF, suggesting that this is one of the important etiologies of vascular dysfunction. Several clinical trials have shown that pharmacological inhibition of the renin-angiotensin-aldosterone system by angiotensin converting enzyme inhibitors, angiotensin II receptor antagonists, or aldosterone receptor antagonists, significantly improves prognosis in this disorder. However, the relationship between the clinical utility of this type of drug and its pharmacological effects on the peripheral vasculature has not been extensively assessed in patients with CHF. The present review summarizes recent reports including our own observations on the pharmacological effects and mechanisms of this type of drug on vascular endothelial function in the peripheral vasculature in human CHF.