Calcium-channel blockers have been shown to be both safe and effective for treatment of patients with systemic hypertension. These drugs reduce peripheral vascular resistance predominantly by the inhibition of transmembrane calcium ion fluxes in vascular smooth muscle, and by this mechanism can reduce elevated blood pressure. To maximize blood pressure lowering efficacy in patients, calcium-channel blockers have also been used in combination with other antihypertensive treatments that have included diuretics, beta-adrenergic blockers, and angiotensin-converting enzyme inhibitors.