Vascular protection with newer antihypertensive agents

Role of calcium Alterations in the structure and function of small arteries may contribute to elevated blood pressure in patients with essential hyper tension and the cardiovascular complications of this disease, Angiotensin I I, endothelin 1, and other peptides, as well as catecholamines, may contrib ute to the altered structure and function of small arteries, in part throug h their effects on intracellular calcium. Intracellular calcium is implicat ed in signal transduction pathways that result in smooth muscle cell growth and contraction and in the release of endothelium-dependent agents involve d in the regulation of vascular function. Vascular effects of newer antihypertensive agents The newer antihypertensiv e agents that affect intracellular calcium pathways either directly or indi rectly, such as calcium antagonists or angiotensin converting enzyme (ACE) inhibitors, may exert vascular protective effects, partly by regressing vas cular remodeling and by correcting endothelial dysfunction, A double-blind trial comparing the effects of the ACE inhibitor cilazapril and the beta-bl ocker atenolol on media:lumen ratio of small gluteal subcutaneous arteries, which was significantly higher in hypertensive patients before treatment t han in normotensive subjects, was corrected after treatment with cilazapril , In contrast, no improvement was seen in the media:lumen ratio of small ar teries in the patients receiving atenolol, even after 2 years of treatment. In another study, treatment with the intrinsically long-acting calcium ant agonist amlodipine resulted in a reduction in forearm minimal vascular resi stance. Patients treated with amlodipine also showed normalized responses o f forearm blood flow to nitric oxide synthase inhibition. Furthermore, pati ents treated with a slow-release formulation of nifedipine exhibited normal media:lumen ratio of small arteries and normal endothelium-dependent relax ation. Conclusions These findings appear very promising; however, it remains to be demonstrated whether the apparently beneficial effects of treatment with l ong-acting calcium antagonists and ACE inhibitors will lead to reductions i n the cardiovascular morbidity and mortality associated with hypertension. J Hypertens 16 (suppl 5):S25-S29 (C) 1998 Lippincott Williams & Wilkins.