Last update:
06-Jun-2005

Hypertension and hyperlipidemia are synergistic factors for cardiovascular events. Both show a degree of crosscorrelation through common mechanisms of pathogenesis, including insulin resistance and endothelial dysfunction. The overall clinical benefits observed with statin therapy appear to be greater than what might be expected from changes in lipid profile alone, suggesting that the beneficial effects of statins may extend beyond their effects on serum cholesterol levels. Indeed, recent experimental and clinical evidence indicates that some of the cholesterol-independent or "pleiotropic" effects of statins involve improving or restoring endothelial function, enhancing the stability of atherosclerotic plaques, and decreasing oxidative stress and vascular inflammation. Many of these pleiotropic effects of statins are mediated by their ability to block the synthesis of important isoprenoid intermediates, which serve as lipid attachments for a variety of intracellular signaling molecules. In particular, the inhibition of small G proteins Rho, Ras, and Rac, whose proper membrane localization and function are dependent on isoprenylation, may play an important role in mediating the direct cellular effects of statins on the vascular wall. Statins have shown a capability to lower blood pressure, in some small clinical trials. However, data from large-scale intervention trials are either absent or ambiguous. Definitive large-scale trials to investigate the antihypertensive effects of statins are required. End point studies examining the interaction of lipid lowering and antihypertensive drugs, to determine optimum combinations, are already under way. This article reviews the evidence that statins may, by their direct modes of action, be antihypertensive and may at least modulate blood pressure.

Key words: Cholesterol, Hypertension, Isoprenylation, Small G proteins, Statins.