Calcium channel blockers, endothelial dysfunction, and combination therapy.

Ivonne H Schulman, Mareena Zachariah, Leopoldo Raij

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Endothelial dysfunction complicates hypertension and is a precursor of atherosclerosis. It is characterized by a reduction in the bioavailability of vasodilators, particularly nitric oxide (NO), and an increase in the activity of vasoconstrictors, including angiotensin (Ang) II and reactive oxygen species (ROS). To the extent that cardiovascular disease is characterized by an imbalance between NO, Ang II, and ROS in the endothelium, modulating the activity of these vasoactive substances has important implications for both the treatment of hypertension and the prevention of atherosclerosis and end organ damage. Accumulating experimental and clinical data suggest that a multitherapy antihypertensive regimen that includes inhibitors of the renin-angiotensin system and calcium channel antagonists may further reduce cardiovascular risk via greater improvements in endothelial function, in addition to the well-documented blood pressure lowering effects. Experimental studies in small and large coronary arteries and in aorta indicate that the calcium channel blocker, amlodipine, stimulates NO generation. These drug-specific actions beyond blood pressure lowering may exert cardio- and vasculoprotective effects by preventing the maladaptive changes that accompany hypertension, namely endothelial dysfunction, upregulation of proinflammatory molecules, vascular smooth muscle cell (VSMC) growth and migration, and increased extracellular matrix deposition, mechanisms that lead to atherosclerotic cardiovascular disease. These effects compliment those of other classes of antihypertensive agents and also 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins), which have also been demonstrated to ameliorate the damaging consequences of endothelial dysfunction and thus reduce the incidence of cardiovascular events.

Original languageEnglish
Pages (from-to)40-45
Number of pages6
JournalAging clinical and experimental research.
Volume17
Issue number4 Suppl
StatePublished - Aug 1 2005
Externally publishedYes

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Calcium Channel Blockers
Nitric Oxide
Hypertension
Angiotensin II
Antihypertensive Agents
Reactive Oxygen Species
Atherosclerosis
Cardiovascular Diseases
Blood Pressure
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Amlodipine
Vasoconstrictor Agents
Renin-Angiotensin System
Vasodilator Agents
Vascular Smooth Muscle
Biological Availability
Smooth Muscle Myocytes
Endothelium
Cell Movement
Extracellular Matrix

ASJC Scopus subject areas

  • Aging

Cite this

Calcium channel blockers, endothelial dysfunction, and combination therapy. / Schulman, Ivonne H; Zachariah, Mareena; Raij, Leopoldo.

In: Aging clinical and experimental research., Vol. 17, No. 4 Suppl, 01.08.2005, p. 40-45.

Research output: Contribution to journalArticle

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