High Blood Pressure and Calcium Antagonism

Abstract

Calcium ions are intimately involved in many aspects of cardiovascular function. Modification of calcium homeostasis therefore represents a key target for pharmacological intervention to achieve therapeutic control of hypertension. The calcium channel blockers (CCBs) act by blocking calcium influx through voltage-dependent L (long-acting) channels without affecting calcium release from the sarcoplasmic reticulum. The effect of blocking these channels is a decrease in the intracellular calcium concentration, which reduces vascular smooth muscle tone. The subsequent decrease in peripheral resistance causes a decrease in systemic blood pressure. The CCBs also decrease myocardial contractility, which decreases myocardial oxygen consumption. Overall, the CCBs at therapeutic doses improve the efficiency of ventricular function. They also have a number of other beneficial effects, including an antiprolifera-tive effect. The CCBs in clinical use vary according to their relative selectivi-ties for vascular and cardiac tissue and their applicability to the treatment of hypertension or ischaemic heart disease. The first-generation CCBs (verapam-il, nifedipine and diltiazem) are associated with a relatively short duration of action and unwanted cardiovascular effects that were related to poor vascular selectivity. In addition, nifedipine was associated with a very rapid onset of action that caused a sudden vasodilation and reflex tachycardia in some patients. The newer second-generation CCBs, for example the dihydropyrid-ines, amlodipine, felodipine and nisoldipine, show greatly improved vascular selectivity and longer durations of action, achieved in part by novel con-trolled-release dosage forms. They bind to target receptors in a slow and sustained fashion, producing a smooth onset of action and 24-hour control of blood pressure. Once-daily dosing of these longer-acting agents improves patient compliance and is associated with a good side-effect profile. The second-generation CCBs are suitable antihypertensive agents for a wide range of patients, including the elderly and black patients, and those with concomitant diseases that preclude the use of other antihypertensives.

Tyrosine Phosphorylation of Human Platelet Plasma Membrane Ca 2+ -ATPase in Hypertension

“…In support of the influx hypothesis, Ca 2ϩ channel blockers have been successfully used to treat hypertension. 13,14 Reduction of peripheral resistance is the primary mechanism by which Ca 2ϩ channel blockers control hypertension, but reduction of platelet Ca 2ϩ influx could also contribute to protection from thrombotic events. 14,15 The Ca 2ϩ channel blocker nifedipine was used by Ahn et al 16 to reduce Ca 2ϩ in the platelets of hypertensives.…”

“…13,14 Reduction of peripheral resistance is the primary mechanism by which Ca 2ϩ channel blockers control hypertension, but reduction of platelet Ca 2ϩ influx could also contribute to protection from thrombotic events. 14,15 The Ca 2ϩ channel blocker nifedipine was used by Ahn et al 16 to reduce Ca 2ϩ in the platelets of hypertensives. Similarly, isradipine was reported to decrease platelet aggregation, 17 even specifically at the site of atherosclerotic lesions.…”

The central mechanism underlying hypertension: a review of the roles of sodium ions, epithelial sodium channels, the renin–angiotensin–aldosterone system, oxidative stress and endogenous digitalis in the brain

“…That is, if the baroreceptor reflex set point is not lowered, the CNS will struggle to restore blood pressure to a higher level. For example, vasodilators such as hydralazine 238 and short-acting dihyropyridine CCBs 239 often cause angina pectoris by increasing sympathetic tone. In fact, although excellent antihypertensive agents are now available, many antihypertensive agents have been screened during the long clinical history of hypertension treatment, only to be rejected because of adverse events.…”

Distinct effects of amlodipine treatment on vascular elastocalcinosis and stiffness in a rat model of isolated systolic hypertension

“…In this regard, reflected waves are very important in determining the morphology of the systolic pulse contour, peak aortic systolic pressure and cardiac afterload [4]. The timing of the reflected wave, favoring its superimposition on the forward wave to produce the final PP, is influenced by peripheral resistance [35], and CCB are well known peripheral vasodilators [36]. To dissociate the effect of amlodipine on calcification and pulse pressure, amlodipine was given for 1 week after 7 weeks of WVK treatment.…”