E L Schiffrin1. 1. Medical Research Council of Canada Multidisciplinary Research Group of Hypertension, Clinical Research Institute of Montreal, University of Montreal, Quebec, Canada.
Abstract
ROLE OF CALCIUM: Alterations in the structure and function of small arteries may contribute to elevated blood pressure in patients with essential hypertension and the cardiovascular complications of this disease. Angiotensin II, endothelin 1, and other peptides, as well as catecholamines, may contribute to the altered structure and function of small arteries, in part through their effects on intracellular calcium. Intracellular calcium is implicated in signal transduction pathways that result in smooth muscle cell growth and contraction and in the release of endothelium-dependent agents involved in the regulation of vascular function. VASCULAR EFFECTS OF NEWER ANTIHYPERTENSIVE AGENTS: The newer antihypertensive agents that affect intracellular calcium pathways either directly or indirectly, such as calcium antagonists or angiotensin converting enzyme (ACE) inhibitors, may exert vascular protective effects, partly by regressing vascular remodeling and by correcting endothelial dysfunction. A double-blind trial comparing the effects of the ACE inhibitor cilazapril and the beta-blocker atenolol on media: lumen ratio of small gluteal subcutaneous arteries, which was significantly higher in hypertensive patients before treatment than in normotensive subjects, was corrected after treatment with cilazapril. In contrast, no improvement was seen in the media: lumen ratio of small arteries in the patients receiving atenolol, even after 2 years of treatment. In another study, treatment with the intrinsically long-acting calcium antagonist amlodipine resulted in a reduction in forearm minimal vascular resistance. Patients treated with amlodipine also showed normalized responses of forearm blood flow to nitric oxide synthase inhibition. Furthermore, patients treated with a slow-release formulation of nifedipine exhibited normal media: lumen ratio of small arteries and normal endothelium-dependent relaxation. CONCLUSIONS: These findings appear very promising; however, it remains to be demonstrated whether the apparently beneficial effects of treatment with long-acting calcium antagonists and ACE inhibitors will lead to reductions in the cardiovascular morbidity and mortality associated with hypertension.
ROLE OF CALCIUM: Alterations in the structure and function of small arteries may contribute to elevated blood pressure in patients with essential hypertension and the cardiovascular complications of this disease. Angiotensin II, endothelin 1, and other peptides, as well as catecholamines, may contribute to the altered structure and function of small arteries, in part through their effects on intracellular calcium. Intracellular calcium is implicated in signal transduction pathways that result in smooth muscle cell growth and contraction and in the release of endothelium-dependent agents involved in the regulation of vascular function. VASCULAR EFFECTS OF NEWER ANTIHYPERTENSIVE AGENTS: The newer antihypertensive agents that affect intracellular calcium pathways either directly or indirectly, such as calcium antagonists or angiotensin converting enzyme (ACE) inhibitors, may exert vascular protective effects, partly by regressing vascular remodeling and by correcting endothelial dysfunction. A double-blind trial comparing the effects of the ACE inhibitor cilazapril and the beta-blocker atenolol on media: lumen ratio of small gluteal subcutaneous arteries, which was significantly higher in hypertensive patients before treatment than in normotensive subjects, was corrected after treatment with cilazapril. In contrast, no improvement was seen in the media: lumen ratio of small arteries in the patients receiving atenolol, even after 2 years of treatment. In another study, treatment with the intrinsically long-acting calcium antagonist amlodipine resulted in a reduction in forearm minimal vascular resistance. Patients treated with amlodipine also showed normalized responses of forearm blood flow to nitric oxide synthase inhibition. Furthermore, patients treated with a slow-release formulation of nifedipine exhibited normal media: lumen ratio of small arteries and normal endothelium-dependent relaxation. CONCLUSIONS: These findings appear very promising; however, it remains to be demonstrated whether the apparently beneficial effects of treatment with long-acting calcium antagonists and ACE inhibitors will lead to reductions in the cardiovascular morbidity and mortality associated with hypertension.