Vascular smooth muscle dilatation

How it works Inhibits calcium movement across cell membranes of cardiac and vascular smooth muscle (dilates coronary arteries, peripheral arteries/arterioles) decreases heart rate, myocardial contractility, slows S A and AV conduction. Decreases total peripheral vascular resistance by vasodilation... 

Muscarinic acetylcholine receptors are present in the mammalian central nervous system (CNS) and in the periphery. Their stimulation produces inhibitory responses such as bradycardia and vascular smooth muscle dilatation, and excitatory responses such as ganglionic depolarization and smooth muscle contraction. Muscarinic receptors of the CNS are involved in motor control, temperature and sleep regulation, and in processes including higher cognitive functions such as memory and learning. 

Amiodarone dilates arteriolar vascular smooth muscle, especiady coronary arteries, and thus exhibits antianginal effects. Its effects on the peripheral vasculature to decrease resistance leads to a decrease in left ventricular stroke work and a decrease in myocardial oxygen consumption. The dmg rarely produces hypotension that requires discontinuation of the dmg (1,2). 

Systemic and coronary arteries are influenced by movement of calcium across cell membranes of vascular smooth muscle. The contractions of cardiac and vascular smooth muscle depend on movement of extracellular calcium ions into these walls through specific ion channels. Calcium channel blockers, such as amlodipine (Norvasc), diltiazem (Cardizem), nicardipine (Cardene), nifedipine (Procardia), and verapamil (Calan), inhibit die movement of calcium ions across cell membranes. This results in less calcium available for the transmission of nerve impulses (Fig. 41-1). This drug action of the calcium channel blockers (also known as slow channel blockers) has several effects on die heart, including an effect on die smooth muscle of arteries and arterioles. These drug dilate coronary arteries and arterioles, which in turn deliver more oxygen to cardiac muscle. Dilation of peripheral arteries reduces die workload of die heart. The end effect of these drug is the same as that of die nitrates. 

Pharmacology The principal pharmacological action of nitrates is relaxation of the vascular smooth muscle and consequent dilation of peripheral arteries and especially the veins. Dilation of the veins promotes peripheral pooling of blood and decreases venous return to the heart, thereby reducing left ventricular end-diastolic pressure and pulmonary capillary wedge pressure (preload). Arteriolar relaxation reduces systemic vascular resistance, systolic arterial pressure, and mean arterial pressure (afterload). Dilation of the coronary arteries also occurs. The relative importance of preload reduction, afterload reduction, and coronary dilation remains undefined. 

One important mechanism of serotonin elimination is the (re-) uptake, e.g. by platelets. Furthermore, serotonin is metabolized by monoaminox-idase to 5-hydroxyindoleacetaldehyde and, subsequently, by an aldehyde dehydrogenase to 5-hydroxyindolacetic acid. The vascular effects of serotonin are complex. The direct interaction with vascular smooth muscle induces a vasoconstriction, whereas the stimulation of 5-HT-receptors on the endothelium induces the release of vasorelaxant factors with a dilatation as a result. An intravenous application of serotonin increases the pressure in the pulmonary circulation. A continuous infusion results... 

Other vasodilators, such as diazoxide and minoxidil, cause dilation of blood vessels by activating potassium channels in vascular smooth muscle. An increase in potassium conductance results in hyperpolarization of the cell membrane, which will cause relaxation of vascular smooth muscle. 

Mechanism of Action An antihypertensive that inhibits calcium movement across cardiacand vascular smooth-muscle cell membranes. Therapeutic Effect Relieves angina by dilating coronary arteries, peripheral arteries, and arterioles. Decreases total peripheral vascular resistance and BP by vasodilation. 

Mecfianism of Action A prostaglandin that dilates systemic and pulmonary arterial vascular beds, alters pulmonary vascular resistance, and suppresses vascular smooth muscle proliferation. Therapeutic Effect Improves symptoms and exercise tolerance in patients with pulmonary hypertension delays deterioration of condition. Pharmacokinetics Protein binding 60%. Metabolized in liver. Primarily excreted in urine minimal elimination in feces. Half-life 20-30 min. 

Direct vasodilators reduce pressure by dilating resistance vessels (arteries) by vascular smooth muscle relaxation (e.g., Ca + channel blockers such as verapamil (4.133) or nifedipine (5.151) vasodilators such as dihydralazine (5.152))... 

Amlodipine is a long-acting calcium channel blocker that inhibits the transmembrane influx of calcium ions into vascular smooth muscle and cardiac muscle. By inhibiting calcium ion influx it directly dilates vascular smooth muscle. 

Direct vasodilators, which reduce pressure by relaxing vascular smooth muscle, thus dilating resistance vessels and—to varying degrees—increasing capacitance as well. 

Sodium nitroprusside is a powerful parenterally administered vasodilator that is used in treating hypertensive emergencies as well as severe heart failure. Nitroprusside dilates both arterial and venous vessels, resulting in reduced peripheral vascular resistance and venous return. The action occurs as a result of activation of guanylyl cyclase, either via release of nitric oxide or by direct stimulation of the enzyme. The result is increased intracellular cGMP, which relaxes vascular smooth muscle (Figure 12-2). 

Diazoxide is an effective and relatively long-acting parenterally administered arteriolar dilator that is occasionally used to treat hypertensive emergencies. Injection of diazoxide results in a rapid fall in systemic vascular resistance and mean arterial blood pressure associated with substantial tachycardia and increase in cardiac output. Studies of its mechanism suggest that it prevents vascular smooth muscle contraction by opening potassium channels and stabilizing the membrane potential at the resting level. 

Serotonin directly causes the contraction of vascular smooth muscle, mainly through 5-HT2 receptors. In humans, serotonin is a powerful vasoconstrictor except in skeletal muscle and heart, where it dilates blood vessels. At least part of this 5-HT-induced vasodilation requires the presence of vascular endothelial cells. When the endothelium is damaged, coronary vessels constrict. As noted previously, serotonin can also elicit reflex bradycardia by activation of 5-HT3 receptors on chemoreceptor nerve endings. A triphasic blood pressure response is often seen following injection of serotonin in experimental animals. Initially, there is a decrease in heart rate, cardiac output, and blood pressure caused by the chemoreceptor response. After this decrease, blood pressure increases as a result of vasoconstriction. The third phase is again a decrease in blood pressure attributed to vasodilation in vessels supplying skeletal muscle. Pulmonary and renal vessels seem especially sensitive to the vasoconstrictor action of serotonin. 

Relaxes vascular smooth muscle, with consequent dilatation of peripheral arteries and veins, resulting in peripheral pooling of blood and decreased venous return to the heart Ultimate effect is a reduction in leftventricular end-diastolic pressure and pulmonar y capillar y wedge pressure... 

Smooth muscles and vascular smooth muscles Prostaglandins E2 and I2 cause arteriolar dilation in the systemic and pulmonary vascular beds. Prostaglandins and E2, as well as thromboxane B2, constrict the human umbilical cord. Leukotrienes C4 and D4, which release prostaglandin E, decrease peripheral vascular resistance. 

Vascular smooth muscle tone is regulated by adrenoceptors consequently, catecholamines are important in controlling peripheral vascular resistance and venous capacitance. Alpha receptors increase arterial resistance, whereas 2 receptors promote smooth muscle relaxation. There are major differences in receptor types in the various vascular beds (Table 9-4). The skin vessels have predominantly receptors and constrict in the presence of epinephrine and norepinephrine, as do the splanchnic vessels. Vessels in skeletal muscle may constrict or dilate depending on whether ffor 13 receptors are activated. Consequently, the overall effects of a sympathomimetic drug on blood vessels depend on the relative activities of that drug at and 8receptors and the anatomic sites of the vessels affected. In addition, Di receptors promote vasodilation of renal, splanchnic, coronary, cerebral, and perhaps other resistance vessels. Activation of the Di receptors in the renal vasculature may play a major role in the natriuresis induced by pharmacologic administration of dopamine. 

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