These findings suggest that these antihypertensive drug classes may have clinically important vasoprotective effects beyond BP lowering. This hypothesis has yet to be supported by the results of randomized, controlled trials.82 Recent evidence suggests that a second angiotensin II receptor subtype (AT2), which is not expressed in the normal vasculature but appears to be induced in the setting of vascular inflammation/hypertension/atherosclerosis, may oppose the vasoconstrictor, antinatriuretic, and proinflammatory effects Because of the apparent vasoprotective effects of AT2 receptor activation, AT2 receptor agonists have been considered for the treatment of hypertension,84 but there is no evidence that they are effective in treating hypertension in humans. Calcium ions (Ca2+ ) are major intracellular mediators of vas- cular smooth muscle cell contraction and inotropic and chro- notropic functions of the heart. Ca2+ enters vascular smooth muscle cells, cardiomyocytes, and pacemaker cells via volt- age-dependent L- and T-type calcium channels. In vascular smooth muscle, the voltage-gated L-type (long-acting, slowly activating) channel allows entry of sufficient Ca2+ for the ini- tiation of contraction by calcium-induced intracellular Ca2+ release from the sarcoplasmic reticulum. Increased intracel- also has atherosclerosis-promoting effects. The dihydropyridine CCBs bind to the 1 subunit of the L-type channel and are highly selective for arterial/arterio- lar tissues, including the coronary arteries, where they are vasodilators. The nondihydropyridine CCBs, including the phenylalkylamines (verapamil-like) and benzothiazepines (diltiazem-like), bind to different sites on the 1 subunit and are less selective for vascular tissue; they have nega- tive chronotropic and dromotropic effects on sinoatrial and atrioventricular nodal conducting tissue and negative ino- tropic effects on cardiomyocytes. 