Endothelium, atherosclerosis and calcium channel blockers.

Probably the most significant advance in cardiovascular medicine over the last two decades has been the identification of endothelial cells as a vasoactive organ. The endothelium plays a primary autocrine/paracrine regulatory role by secreting substances that control both vascular tone and structure. The dysfunctioning endothelium, which is characteristic of essential hypertension and most of the cardiovascular risk factors, is a major promoter for atherothrombosis and, consequently, cardiovascular treatment. One of most relevant mechanisms of endothelial dysfunction is oxidative stress production, which causes nitric oxide breakdown. The clinical manifestations of atherosclerosis are by far the prevailing cause of morbidity and mortality in hypertensive patients. Various clinical studies have shown the beneficial effects of calcium channel blockers on endothelial dysfunction. The potential mechanism by which calcium channel antagonists could exert their beneficial activity on endothelial dysfunction is very unlikely to be a calcium-dependent mechanism since endothelial cells do not express voltage-operated calcium channels. Experimental evidence suggests that calcium channel antagonists exert an anti-oxidant effect and therefore could protect endothelial cells against free-radical injury. Nifedipine is the calcium channel blocker, which improves endothelial nitric oxide availability, antagonises endothelin 1, restores endothelial permeability and low-density lipoprotein deposition. Calcium antagonists have demonstrated anti-atherogenic properties in various dinical studies. Calcium antagonists--in addition to their primary action in lowering blood pressure influence numerous cellular process involved in early atherogenesis. All calcium channel blockers do not offer same benefit of reversal of endothelial dysfunction. Amlodipine does not seem to be as effective as nifedipine in terms of atheroprotection. With nifedipine, the overall risk of cardiovascular events decreased significantly. Therefore, nifedipine (long-acting formulation) remains the first choice calcium channel blocker in cardiovascular therapeutics--today and tomorrow.

Complications of hypertension as encountered by primary care physician.

Hypertension is a common clinical problem with great implications for public health. It is a silent killer and often remains asymptomatic. So regular BP check-up is a must. Complications of untreated hypertension include ventricular hypertrophy, heart failure and accelerated atherosclerosis, cerebrovascular disease and stroke, renal failure and retinopathy. Primary care physicians have immense duty to perform in this regard because they are the first to encounter them in various stages of the disease. Hypertension can present per se or in emergencies (as in crisis) or in disguise of a complication (like anaemia and renal failure). Control of hypertension and delaying the development of complications should be their first goal. Lastly, some hypertensives with complications may require referral to advanced centres.