Effects of calcium channel and renin-angiotensin system blockade on intravascular and neurohormonal mechanisms of hypertensive vascular disease

Several classes of antihypertensive drugs have been shown to improve vascular function through mechanisms other than reducing blood pressure (BP) alone. Certain dihydropyridine calcium channel blockers (CCBs) and inhibitors of the renin-angiotensin system (RAS) increase nitric oxide (NO) bioavailability and decrease oxidative stress, thereby improving endothelial activity and vascular function. Pulse wave analyses have shown that these agents reduce the impact of pressure wave reflections on central systolic BP (SBP), consistent with a decrease in arterial stiffness. The complementary vascular mechanisms of these drug classes suggest that combination therapy may be effective for improving clinical outcomes. In animal model studies, combination calcium channel/RAS blockade has been shown to be more effective in improving endothelial dysfunction than treatment with drugs from either class alone. Furthermore, results from recent clinical trials suggest a greater reduction in central aortic SBP, pulse pressure, and cardiovascular events with calcium channel/RAS blockade vs. beta-blocker/diuretic therapy. These studies support the potential benefit of combination calcium channel and RAS blockade in the prevention and treatment of cardiovascular disease.