All Ca2+ antagonists yet developed are vasodilators. Vasodilation is a result of the uncoupling of the contractile mechanism of vascular smooth muscle, which requires Ca2+. Coronary artery muscle tone is reduced in healthy humans but is particularly pronounced in a condition of coronary spasm. Peripheral arteriole resistance is reduced more than venous beds. The vasodilatory effect of these drugs is the basis for their use in the control of angina and hypertension.13
Although verapamil, nifedipine, and diltiazem can cause vasodilation, they are not equally effective at blocking the Ca2+ channels found in various tissues. The phenyl-alkylamine verapamil and the benzothiazepine diltiazem have both cardiac and vascular actions. These drugs have antiarrhythmic, antianginal, and antihypertensive activity. They depress the cardiac neural network, and so slow sinus node automaticity, prolong atrioventricular (AV) nodal conductance, and depress myocardial contractility, as well as reduce peripheral vascular resistance to prevent a coronary vascular spasm. Nifedipine and other 1,4-dihy-dropyridines are more effective at causing vasodilation than affecting pacemaker and tension responses in the heart. This is especially important because selectivity occurs as a consequence of disease states. Hypertensive smooth muscle is more sensitive to Ca2+ channel blockers than is normotensive tissue.14 This makes verapamil and diltiazem more useful in ischemic conditions, because they have a more profound effect on cardiac muscle calcium channels.15
The inhibition of Ca2+ influx into cardiac tissue by Ca2+ antagonists is also the basis for the use of these drugs as antiarrhythmic agents. The Ca2+ channel blockers dampen Ca2+-dependent automaticity in the regular pacemaker cells in the sinoatrial (SA) node and depress the origination of ectopic foci. Calcium antagonists can block reentry pathways in myocardial tissue, an integral component of arrhythmias. Numerous side effects in the heart, such as bradycardia, decreased cardiac contractility, and reduced AV conductance, are traced to Ca2+ channel-blocking activity.
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Your heart pumps blood throughout your body using a network of tubing called arteries and capillaries which return the blood back to your heart via your veins. Blood pressure is the force of the blood pushing against the walls of your arteries as your heart beats.Learn more...