Calcium-channel modulators for cardiovascular disease

Abstract

It is generally accepted that hypertension doubles the risk of cardiovascular disease, of which coronary heart disease is the most common and lethal. Hypertension is a predisposing factor for the development of stroke, peripheral arterial disease, heart failure and end-state renal disease. Atherosclerosis-causing coronary heart disease is related to the severity of hypertension. Inhibition of calcium entry reduces the active tone of vascular smooth muscle and produces vasodilatation. This pharmacological action has been the basis for the use of calcium-channel blockers (CCBs) for the management of hypertension. Other drug families may achieve this: diuretics, beta-blockers, angiotensin-converting enzyme inhibitors, angiotensin-receptor antagonists. Cardiovascular hypertrophy and atherosclerosis are major complications related to high blood pressure. Cardiac hypertrophy is considered as an independent risk factor associated with abnormalities of diastolic function and can result in heart failure. Atherosclerosis is associated with activation of innate immunity. Atherosclerosis is expressing itself not only as coronary heart disease, but as a cerebrovascular and peripheral arterial disease. By impairing physiological vasomotor function, atherosclerosis includes ultimately necrosis of myocardium. CCBs reduce blood pressure. Do they prevent the progress of the main complications of hypertension? This major question is the matter of the present paper.

Herbal medicines as diuretics: A review of the scientific evidence

“…Hypertension is considered to be a predisposing factor for stroke, coronary heart disease, peripheral arterial disease, heart failure and end-state renal disease (Williams et al, 2004;Godfraind, 2006). Common clinical strategies to achieve a lowering of blood pressure include the use of angiotensin converting enzyme (ACE) inhibitors, beta blockers, calcium channel blockers (or CCB's) and diuretics (Williams et al, 2004;Gallagher et al, 2006).…”

“…Beta receptor blockers act to counter the stimulatory effects of vascular and cardiac noradrenergic receptors (Rabbia et al, 2001). CCB's inhibit calcium entry thus decreasing the tone of vascular smooth muscle and promoting vasodilatation (Godfraind, 2006). Diuretics work by promoting the expulsion of urine (measured as the urine volume [UV] excreted) and urinary sodium (UNa) from the body and this helps reduce the volume of blood circulating through the cardiovascular system (Reyes and Taylor, 1999;Williams et al, 2004;Gallagher et al, 2006).…”

Nifedipine improves the migratory ability of circulating endothelial progenitor cells depending on manganese superoxide dismutase upregulation

“…In the same time, nifedipine lyposolubility could explain the difference of effect obtained on endothelial lineage when treated with the hydrophilic molecule amlodipine [35]. Accordingly, the antioxidant action of calcium channel blocker on endothelial cells was observed only with lipophilic dihydropyridine calcium antagonists [36,37].…”

Liquid Chromatography/Positive-Ion Electrospray Tandem Mass Spectrometry Assay for Nisoldipine in Human Plasma and Its Application to a Pharmacokinetic Study

“…Among the calcium channel antagonists, the 1,4-dihydropyridines are the most commonly used, not only for their ability to lower blood pressure but also for their multiple pharmacological effects, such as protecting the renal system, inhibiting ischemia, preventing platelet aggregation, and regressing left ventricular pressure. [1][2][3] Nisoldipine, (AE)3-isobutyl-5-methyl-1,4-dihydro-2,6-dimethyl-4-(2 0 -nitrophenyl)pyridine-3,5-dicarb-oxylate, a strong calcium antagonist of 1,4-dihydropyridine-sensitive calcium channels, can reduce vascular resistance and blood pressure by inhibiting calcium uptake of the myocardium and smooth muscle cells. Nisoldipine is commonly used in clinical practice to treat hypertension and coronary heart disease.…”