Arteriolar vasodilators

Possible uses. Arteriolar vasodilators are given to lower blood pressure in hypertension (p. 312), to reduce cardiac work in angina pectoris (p. 308), and to reduce ventricular afterload (pressure load) in cardiac failure (p. 132). Venous vasodilators are used to reduce venous filling pressure (preload) in angina pectoris (p. 308) or cardiac failure (p. 132). 

Vascular smooth muscle. PGE2 and PGI2 produce arteriolar vasodilation PGp2a, venoconstriction. 

Minoxidil, an antihypertensive agent, produces arteriolar vasodilation by an unknown mechanism. In limited clinical studies, minoxidil increases penile rigidity and has been used in the long-term treatment of organic impotence. 

The answer is d. (Hardman, pp 192-193.) Nicotine is a depolarizing ganglionic blocking agent that initially stimulates and then blocks nicotinic muscular (NM) (skeletal muscle) and nicotinic neural (NN) (parasympathetic ganglia) cholinergic receptors. Blockade of the sympathetic division of the autonomic nervous system (ANS) results in arteriolar vasodilation, bradycardia, and hypotension. Blockade at the neuromuscu-... 

Substance P is the most important member of the tachykinin family. It exerts a variety of incompletely understood central actions that implicate the peptide in behavior, anxiety, depression, nausea, and emesis. It is a potent arteriolar vasodilator, producing marked hypotension in humans and several animal species. The vasodilation is mediated by release of nitric oxide from the endothelium. Conversely, substance P causes contraction of venous, intestinal, and bronchial smooth muscle. It also stimulates secretion by the salivary glands and causes diuresis and natriuresis by the kidneys. 

When injected intravenously, kinins produce a rapid fall in blood pressure that is due to their arteriolar vasodilator action. The hypotensive response to bradykinin is of very brief duration. Intravenous infusions of the peptide fail to produce a sustained decrease in blood pressure prolonged hypotension can only be produced by progressively increasing the rate of infusion. The rapid reversibility of the hypotensive response to kinins is due primarily to reflex increases in heart rate, myocardial contractility, and cardiac output. In some species, bradykinin produces a biphasic change in blood pressure—an initial hypotensive response followed by an increase above the preinjection level. The increase in blood pressure may be due to a reflex activation of the sympathetic nervous system, but under some conditions, bradykinin can directly release catecholamines from the adrenal medulla and stimulate sympathetic ganglia. Bradykinin also increases blood pressure when injected into the central nervous system, but the physiologic significance of this effect is not clear, since it is unlikely that kinins cross the blood-brain barrier. 

Hydralazine was one of the first orally active antihypertensive drugs marketed in the United States. Its structure is shown in Figure 12.4. Initially, the drug was used infrequently because of its propensity to produce reflex tachycardia and tachyphylaxis. However, with a better understanding of the compensatory cardiovascular responses that accompany use of arteriolar vasodilators (the drug has little or no effect on venous smooth muscle), hydralazine was combined with sympatholytic agents and diuretics with greater therapeutic success. 

Nifedipine [nye FED i peen] functions mainly as an arteriolar vasodilator. This drug has minimal effect on cardiac conduction or heart rate. Nifedipine is administered orally and has a short half-life (about 4 hours) requiring multiple dosing. The vasodilation effect of nifedipine is useful in the treatment of variant angina caused by spontaneous coronary spasm. Nifedipine can cause flushing, headache, hypotension, and peripheral edema as side effects of its vasodilation activity. The drug may cause reflex tachycardia if peripheral vasodilation is marked resulting in a substantial decrease in blood pressure. 

Diazoxide [dye az OX ide] is a direct-acting arteriolar vasodilator. It has vascular effects like those of hydralazine. For patients with coronary insufficiency, diazoxide is administered intravenously with a p-blocker, which diminishes reflex activation of the heart. Diazoxide is useful in the treatment of hypertensive emergencies, hypertensive encephalopathy, and eclampsia. Excessive hypotension is the most serious toxicity. 

Despite the development of portosystemic collaterals, which ought to lead to a fall in portal hypertension, the hyperdynamic circulation accompanied by splanchnic vasodilation (= increased cardiac output, decreased systemic vascular resistance, hypervolaemia, systemic arteriolar vasodilation) maintains portal hypertension in both the splanchnic and systemic vascular systems. (10, 47, 87) The hyperdynamic circulation is either the cause... 

Dipyridamole is also a potent coronary arteriolar vasodilator, perhaps by opening of vascular K tp channels (2). However, the Food and Drug Administration withdrew conditional approval for certain drug products containing dipyridamole, because of a lack of sufficient evidence of effectiveness in the long-term therapy of angina pectoris (3). 

Dopamine Afferent+efferent arteriolar vasodilation Dependence on balance of constrictors and dilators [237]... 

Chlorothiazide rat, dog, man i, or no change i, or no change Decline in SNGFR, when it occurs, may be related to t proximal intratubular pressure, volume contraction or afferent arteriolar vasodilation... 

Direct-acting arteriolar vasodilators relax the smooth muscles of the blood vessels, causing vasodilation, which results in an increase in blood flow to the brain and kidneys. Direct-acting arteriolar can be combined with diuretics to decrease the edema. 

The principle of dipyridamole and adenosine thallium imaging is related to their coronary arteriolar vasodilator properties. Dipyridamole inhibits adenosine cellnlar renptake, resulting in increased concentrations of adenosine in the blood and tissues. Adenosine is a potent coronary artery vasodilator and can increase perfusion four to five times over baseline. Areas distal to a coronary artery obstruction will show a relative hypoperfnsion compared with normal coronary arteries because there is reduced perfusion pressure owing to preferential perfusion of normal segments over stenotic segments. Acutely, these areas will appear as cold spots, but on the redistribution scans, the defects will fill, indicating viable bnt jeopardized myocardium. 

Local autoregulatory processes maintain adequate tissue oxygenation. When tissue oxygen demand is normal to low, the local arteriolar bed remains relatively vasoconstricted. However, increases in metabolic demand trigger arteriolar vasodilation that lowers peripheral vascular resistance and increases blood flow and oxygen delivery through autoregulation. 

The mechanism by which trazodone produces an erection is not clear. It likely acts peripherally to antagonize a-adrenergic receptors. As a result, a predominant cholinergic effect results, which causes peripheral arteriolar vasodilation and relaxation of cavernosal tissues, which enhances blood filling of the corpora. Intracavernosal injection of trazodone in experimental studies supports this likely mechanism. ... 

Arteriolar vasodilation via K+ channel opening. Reflex tachycardia —> T CO, T renin secretion. Used IV for hypertensive emergencies. 

Epoxygenase metabolites contribute to nitric oxide-independent afferent arteriolar vasodilation in response to bradykinin. J. Vase. Res. 38, 247-255. 

Minoxidil (loniten) is efficacious in patients with the most severe and drug-resistant forms of hypertension. A small fraction of minoxidil is metabolized by hepatic sulfotransferase to the active molecule, minoxidil N-O sulfate. Minoxidil sulfate activates the ATP-modulated channel in smooth muscle, causing hyperpolarization and relaxation of arteriolar smooth muscle. Minoxidil produces arteriolar vasodilation with essentially no effect on capacitance vessels. Minoxidil preferentially increases blood flow to skin, skeletal muscle, the GI tract, and the heart. The disproportionate increase in blood flow to the heart may have a metabolic basis, in that administration of minoxidil is associated with a reflex increase in myocardial contractility and in cardiac output. The cardiac output can increase by as much as three- to fourfold, primarily due to enhanced venous return to the heart. The increased venous return probably results from enhanced flow in vascular beds with a fast response for venous return to the heart. The adrenergic increase in myocardial contractility contributes to the increased cardiac output, but is not the predominant factor. The renal effects of minoxidil are complex it dilates renal arteries, but systemic hypotension produced by the drug actually can decrease renal blood flow. Renal function usually improves in patients who take minoxidil for the treatment of hypertension, especially if renal dysfunction is secondary to hypertension. Minoxidil potently stimulates renin secretion, an effect mediated by renal sympathetic stimulation. 

Ms. Green has severe hypertension and is to receive minoxidil. Minoxidil is a powerful arteriolar vasodilator that does not act on autonomic receptors. When used in severe hypertension, its effects would probably include... 

Substance P is an arteriolar vasodilator that is also a pain-mediating neurotransmitter. The answer is (I),... 

Substance P, an undecapeptide, is a member of the tachykinin peptide group. It is an important sensory neuron transmitter in the ENS and, of course, in primary afferents involved in nociception. Substance P contracts intestinal and bronchiolar smooth muscle but is an arteriolar vasodilator (possibly via NO release). It may also play a role in renal and salivary gland functions. 

Antihypertensive arteriolar vasodilator, orally active used in severe HTN, CHF. Tox tachycardia, salt and water retention, lupus-like syndrome. 

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