Nitric oxide vasodilator

Whittle, B.J.R. (1990). Role of endothelium-derived vasodilator, nitric oxide and neuropeptides in gastric integrity. Gastroenterology 98, A147. 

Nerve receptors, or nociceptors, may release substance P, a peptide that causes vasodilation when released.20 This dilation occurs mainly through substance P-induced production of the vasodilator nitric oxide. Substance P also generates the release of histamine, leading to bradykinin release and activation of an inflammatory process. Capsaicin relieves pain by stimulating the release of substance P from sensory nerve fibers, which ultimately depletes stores of substance P. 

Apart from being a vasodilator, nitric oxide is also a potent inhibitor of neutrophil adhesion to the vascular endothelium. This is due to the inhibitory effect of nitric oxide on the expression of adhesion molecules on the endothelial surface. The role of nitric oxide in protecting the endothelium has been demonstrated by studies that showed that treatment with nitric oxide donors protects against ischemia- and reperfusion-mediated endothelial dysfunction. 

The mechanism of the acute kidney injury is thought to be multifactorial and similar to other cases of myoglobinuric renal failure [118, 121-126]. These factors include obstruction of tubules, toxic effects of the pigment or iron on renal tubular cells and altered hemodynamics in association with inhibition of the vasodilator nitric oxide by myoglobin. Experimental animals exposed to heme pigment have increases in the renal synthesis of both heme oxidase and ferritin [125]. This allows for more rapid heme degradation and greater sequestration of potentially toxic iron by the tubular cells [125]. Whether narcotics or the hypotensive, hypoxic environment associated with rhabdomyolysis interfere with these protective effects of the kidney is unknown. 

A dose-related hemodynamic mechanism is likely dnring the initial months of therapy since renal fnnction improves rapidly following dose rednction. Reversible vasoconstriction and injnry to glomerular afferent arterioles occurs, possibly due to increased activity of vasoconstrictors, including thromboxane A2, endothelin, and the sympathetic nervous system, or diminished activity of vasodilators, nitric oxide, or prostacyclin. Vasoconstriction due to increased renin-angiotensin system activity may also contribute. In contrast renal arteriolar hyaflnization and chronic renal ischemia as well as increased extracellular matrix synthesis appear to contribute to cyclosporine-induced chronic kidney disease. ... 

Oxidative stress has been suggested to contribute to the etiology of hypertension [86-90]. Subjects with increased blood pressure have been noted to have decreased plasma antioxidants [91-93]. Epidemiological and clinical trial data also suggest that antioxidant-rich diets appear to reduce blood pressure and may reduce cardiovascular risk [94]. A direct involvement of oxidants in the hypertensive response of the vasculature as well as the consequence of oxidative inactivation of the potent vasodilator, nitric oxide (NO) has been implicated [95]. Oxidative stress has been implicated both as a causative as well as a consequence of hypertension. 

Nitric Oxide. Nitric oxide [10102-43-9] NO, is a ubiquitous intracellular and intercellular messenger serving a variety of functions including vasodilation, cytotoxicity, neurotransmission, and neuromodulation (9). NO is a paramagnetic diatomic molecule that readily diffuses through aqueous and hpid compartments. Its locus of action is dictated by its chemical reactivity and the local environment. NO represents the first identified member of a series of gaseous second messengers that also includes CO. 

Cyclic GMP is made from GTP by the enzyme gua-nylyl cyclase, which exists in soluble and membrane-bound forms. Each of these isozymes has unique physiologic properties. The atriopeptins, a family of peptides produced in cardiac atrial tissues, cause natriuresis, diuresis, vasodilation, and inhibition of aldosterone secretion. These peptides (eg, atrial natriuretic factor) bind to and activate the membrane-bound form of guanylyl cyclase. This results in an increase of cGMP by as much as 50-fold in some cases, and this is thought to mediate the effects mentioned above. Other evidence links cGMP to vasodilation. A series of compounds, including nitroprusside, nitroglycerin, nitric oxide, sodium nitrite, and sodium azide, all cause smooth muscle re-... 

Lippe, I.T., Stabentheiner, A. and Holzer, P. (1993a). Role of nitric oxide in the vasodilator but not exudative component of mustard oil-induced inflammation in rat skin. Agents Actions 38, c22-24. 

Warren, J.B., Loi, R.K. and Coughlan, M.L. (1993). Involvement of nitric oxide synthase in the delayed vasodilator response to ultraviolet light irradiation of rat skin in vriv. Br. J. Pharmacol. 109, 802-806. 

Nitric oxide, a vasodilatory hormone released by the endothelium, is found in higher concentrations in HF patients and provides two main benefits in HF vasodilation and neurohormonal antagonism of endothelin.9 Nitric oxide s production is affected by the enzyme inducible nitric oxide synthetase (iNOS), which is up-regulated in the setting of HF, likely due to increased levels of angiotensin II, norepinephrine, and multiple cytokines. In HF, the physiologic response to nitric oxide appears to be blunted, which contributes to the imbalance between vasoconstriction and vasodilation. 

Increased intrahepatic resistance to portal flow increases pressure on the entire splanchnic bed an enlarged spleen (splenomegaly) is a common finding in cirrhotic patient and can result in thrombocytopenia due to splenic sequestration of the platelets. Portal hypertension mediates systemic and splanchnic arterial vasodilation through production of nitric oxide and other vasodilators in an attempt to counteract the increased pressure gradient. Nitric oxide causes a fall in systemic arterial pressure unfortunately, this activates both the renin-angiotensin-aldosterone and sympathetic nervous systems and... 

As previously discussed, increased portal pressure triggers the release of nitric oxide to directly vasodilate the splanchnic arterial bed and decrease portal pressure. Unfortunately, nitric oxide also dilates the systemic arterial system, causing a decrease in blood pressure and a decrease in renal perfusion by lowering the effective intravascular volume. The kidney reacts by activating the renin-angiotensin-aldosterone system, which increases plasma renin activity, aldosterone production, and sodium retention. This increase in intravascular volume furthers the imbalance of intravascular oncotic pressure, allowing even more fluid to escape to the extravascular spaces. 

Results of a more recent series of investigations suggest that lead may cause hypertension in rats by increasing reactive oxygen species, which act as vasoconstrictors, and decreasing nitric oxide, a vasodilator released by the endothelium. The reactive oxygen species may be the hydroxyl radical, and did not appear to be the superoxide anion (Ding et al. 1998). 

Indicate the source, factors regulating the release, and physiological significance of the following vasodilators prostacyclin, nitric oxide, and atrial natriuretic peptide... 

The vascular endothelium produces a number of substances that are released basally into the blood vessel wall to alter vascular smooth muscle tone. One such substance is endothelin (ET-1). Endothelin exerts its effects throughout the body, causing vasoconstriction as well as positive inotropic and chronotropic effects on the heart. The resulting increases in TPR and CO contribute to an increase in MAP. Synthesis of endothelin appears to be enhanced by many stimuli, including Ag II, vasopressin, and the mechanical stress of blood flow on the endothelium. Synthesis is inhibited by vasodilator substances such as prostacyclin, nitric oxide, and atrial natriuretic peptide. There is evidence that endothelin is involved with the pathophysiology of many cardiovascular diseases, including hypertension, heart failure, and myocardial infarction. Endothelin receptor antagonists are currently available for research use only. 

First described in the 1980s as "endothelium-derived relaxing factor," nitric oxide (NO) is a vasodilator believed to play a role in regulation of blood pressure under physiologic and pathophysiological conditions. For example, inhibition of NO synthesis under normal conditions and during septic shock results in a significant elevation of blood pressure. 

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