Nitric Oxide, Donors, Inhibitors

Name the enzyme responsible for the synthesis of nitric oxide in tissues. 

List the major beneficial and toxic effects of endogenous nitric oxide. 

List two drugs that spontaneously or enzymatically break down in the body to release nitric oxide. 

Endotheiium-derived relaxing factor, EDRF A mixture of nitric oxide and other vasodiiator substances synthesized in vascu-iar endotheiium 

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Physiologically, in both normal and hypertensive individuals, blood pressure is maintained by moment-to-moment regulation of cardiac output and peripheral vascular resistance, exerted at three anatomic sites (Figure 11-1) arterioles, postcapillary venules (capacitance vessels), and heart. A fourth anatomic control site, the kidney, contributes to maintenance of blood pressure by regulating the volume of intravascular fluid. Baroreflexes, mediated by autonomic nerves, act in combination with humoral mechanisms, including the renin-angiotensin-aldosterone system, to coordinate function at these four control sites and to maintain normal blood pressure. Finally, local release of hormones from vascular endothelium may also be involved in the regulation of vascular resistance. For example, nitric oxide (see Chapter 19 Nitric Oxide, Donors, Inhibitors) dilates and endothelin-1 (see Chapter 17 Vasoactive Peptides) constricts blood vessels. 

Katzung PHARMACOLOGY, 9e > Section IV. Drugs with Important Actions on Smooth Muscle > Chapter 19, Nitric Oxide, Donors, Inhibitors > == =... 

Organic nitrites (amyl nitrite and isobutyl nitrite) cause dizziness, giddiness, rapid heart rate, lowered blood pressure, "speeding," and flushing of the skin. These effects last only a few minutes and can readily be repeated. The main effect of the drug on sexual performance is probably to enhance or prolong erection through the release of nitric oxide in the corpora cavernosa (see Chapter 19 Nitric Oxide, Donors, Inhibitors). 

He flJTH npoflaacM CKan m fleacaBio-KOHBepciiH MVCAKfl 3t 4>poHT.py >- NITRIC OXIDE. DONORS, INHIBITORS / 181... 

Muscara, M.N. and Wallace, J.L. (1999) Nitric oxide. V. Therapeutic potential of nitric oxide donors and inhibitors. American Journal of Physiology 276, G1313-1316. 

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. 

Neutral endopeptidase inhibitors. Nitric oxide donors, Endothelin receptor antagonists... 

Nitric oxide donors and their clinical relevance as inhibitors of platelet activation... 

Squadrito F, Altavilla D, Squadrito G, Campo GM, loculano M, Canale P, Rossi F, Saitta A and Caputi AP, Effects of S-ethylisothiourea, a potent inhibitor of nitric oxide synthase, alone or in combination with a nitric oxide donor in splanchnic artery occlusion shock. Br J Pharmacol 119(1) 23-8, 1996. 

Active as inhibitor on two stage carcinogenesis test of mouse skin tumors induced by nitric oxide donor (NOR 1) and TPA. [44]... 

Androgen-independent prostate cancer cell lines exhibit high levels of Wnt/B-catenin signaling. The non-steroidal anti-inflammatory dmg, sulindac sulfide, celecoxib, the cyclooxygenase-2 inhibitor, the nitric oxide-donor aspirin-derivative. 

Feelisch, M., Kotsonis, P., Siebe, J., Clement, B., Sehmidt, H. H. (1999) The soluble guanylyl cyclase inhibitor lH-[l,2,4]oxadiazolo[4,3,-a] quinoxalin-l-one is a nonselective heme protein inhibitor of nitrie oxide synthase and other eytoehrome P-450 enzymes involved in nitric oxide donor bioaetivation. Mol. Pharmacol. 56 243-253. 

The relationship between NO, endothehns, and prostaglandins have been explored in isolated pancreatic tissue from streptozocin-diabetic rats (Gon-zAlez et al. 1999). The addition of nitric oxide synthase inhibitors (1 mM h/°-nitro-L-arginine methyl ester or 600 pM h/°-monomethyl-L-arginine) in the incubating medium reduced and NO donors (300 iM SIN-1 or 100 iM spermine NONOate) increased endothehn levels in pancreatic slices from control and diabetic animals. 

Ribeiro, A. C. Kapas, L. (2003). Intra-suprachiasmatic nucleus (SCN) microinjection of a nitric oxide (NO) donor and NO synthase inhibitor affects sleep in rats. 

Cytochrome cdj needs three things to reduee nitrite to nitric oxide, substrates nitrite and protons plus eleetrons. The first two are simply supplied from the environment but where do the eleetrons eome from Cytochrome cdi derives its electrons from the eleetron transport system in the cytoplasmic membranes of baeteria. Thus, for example, eleetrons ean originate from NADH and pass via NADH dehydrogenase, ubiquinone/ubiquinol and the cytochrome bc eomplex to nitrite reduetase (Berks et al., 1995 Zumft, 1997). It is known that the eytoehrome bc eomplex is used beeause electron transfer from physiologieal donors, e.g. NADH, to nitrite reduetase is blocked by specific inhibitors, e.g. myxothiazol, of this complex. An important issue arises when we eonsider how electrons are transferred from the cytochrome fccj complex to eytoehrome cd, which, recall, is a water-soluble protein located in the periplasm. The structure of the cytochrome be I complex (determined for the mitoehondrial protein but we can assume that the bacterial counterparts are similarly organised) shows that the... 

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