Prostaglandin H Synthase and Vascular Function

Davidge, Sandra T.

doi:10.1161/hh2001.098351

Cited by 207 publications

(177 citation statements)

References 165 publications

(145 reference statements)

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“…A recent report, however, raises a possibility that AKRs 1C1 and 1C2 may also be able to catalyze the conversion of PGE 2 to PGF 2α (Dozier et al, 2008). PGD 2 and PGE 2 each have important biological functions such as constriction of smooth muscles and vasoconstriction, body temperature regulation, sleep-wake regulation in the brain (Oka, 2004;Huang et al, 2007;Davidge, 2001), thus their reduction to PGF 2 may play a role in regulating their level in addition to the synthesis of biologically active PGF 2 , indicating that AKR1C3 can be an important regulator of these physiological processes.…”

Section: C) Prostaglandinsmentioning

confidence: 99%

The Aldo-Keto Reductase Superfamily and its Role in Drug Metabolism and Detoxification

Barski

Tipparaju

Bhatnagar

2008

Drug Metabolism Reviews

436

340

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The Aldo-Keto Reductase (AKR) superfamily comprises of several enzymes that catalyze redox transformations involved in biosynthesis, intermediary metabolism and detoxification. Substrates of the family include glucose, steroids, glycosylation end products, lipid peroxidation products, and environmental pollutants. These proteins adopt a (β/α) 8 barrel structural motif interrupted by a number of extraneous loops and helixes that vary between proteins and bring structural identity to individual families. The human AKR family differs from the rodent families. Due to their broad substrate specificity, AKRs play an important role in the Phase II detoxification of a large number of pharmaceuticals, drugs, and xenobiotics.

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Section: C) Prostaglandinsmentioning

confidence: 99%

The Aldo-Keto Reductase Superfamily and its Role in Drug Metabolism and Detoxification

Barski

Tipparaju

Bhatnagar

2008

Drug Metabolism Reviews

436

340

View full text Add to dashboard Cite

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“…PGI 2 is an antithrombotic and vasodilator molecule that can decrease vascular remodeling and cholesterol uptake (51,52). This is particularly evident from the fact that disruption of the prostacyclin receptor gene leads to increased intimamedium ratio in response to vascular injury and promotes initiation and progression of atherosclerosis in hyperlipidemic mouse (53,54), suggesting a protective role for prostacyclin in vascular remodeling.…”

Section: Figurementioning

confidence: 99%

“…This is particularly evident from the fact that disruption of the prostacyclin receptor gene leads to increased intimamedium ratio in response to vascular injury and promotes initiation and progression of atherosclerosis in hyperlipidemic mouse (53,54), suggesting a protective role for prostacyclin in vascular remodeling. TXA 2 , in contrast, is a prothrombotic and vasoconstricting agent, and enhances vascular remodeling (51,52). Because PGI 2 and TXA 2 exert opposing influences in the cardiovascular system, the up-regulation of the expression of COX-2, PGE 2 synthase, and PGI 2 synthase in HCAEC by histamine emphasizes its importance in the maintenance of vascular integrity.…”

Section: Figurementioning

confidence: 99%

Histamine Directly and Synergistically with Lipopolysaccharide Stimulates Cyclooxygenase-2 Expression and Prostaglandin I2 and E2 Production in Human Coronary Artery Endothelial Cells

Tan

Essengue

Talreja

et al. 2007

The Journal of Immunology

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Although histamine plays an essential role in inflammation, its influence on cyclooxygenases (COX) and prostanoid homeostasis is not well understood. In this study, we investigated the effects of histamine on the expression of COX-1 and COX-2 and determined their contribution to the production of PGE2, prostacyclin (PGI2), and thromboxane A2 in human coronary artery endothelial cells (HCAEC). Incubation of HCAEC monolayers with histamine resulted in marked increases in the expression of COX-2 and production of PGI2 and PGE2 with no significant change in the expression of COX-1. Histamine-induced increases in PGI2 and PGE2 production were due to increased expression and function of COX-2 because gene silencing by small interfering RNA or inhibition of the catalytic activity by a COX-2 inhibitor blocked prostanoid production. The effects of histamine on COX-2 expression and prostanoid production were mediated through H1 receptors. In addition to the direct effect, histamine was found to amplify LPS-stimulated COX-2 expression and PGE2 and PGI2 production. In contrast, histamine did not stimulate thromboxane A2 production in resting or LPS-activated HCAEC. Histamine-induced increases in the production of PGE2 and PGI2 were associated with increased expression of mRNA encoding PGE2 and PGI2 synthases. The physiological role of histamine on the regulation of COX-2 expression in the vasculature is indicated by the findings that the expression of COX-2 mRNA, but not COX-1 mRNA, was markedly reduced in the aortic tissues of histidine decarboxylase null mice. Thus, histamine plays an important role in the regulation of COX-2 expression and prostanoid homeostasis in vascular endothelium.

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“…The source of the increased cyclooxygenase activity that produces the elevated levels of TxA 2 and PGI 2 in vessels of animals on high-salt diet is most likely in the endothelium, since the expression of COX-1 and COX-2 is up to 20 times greater in the endothelium than in the smooth muscle cells (5). In addition, thromboxane can be produced by the endothelium, in addition to its primary source of production in the platelets (5).…”

Section: Effect Of High-salt Diet On Electrical and Mechanical Responmentioning

confidence: 99%

High-salt diet impairs vascular relaxation mechanisms in rat middle cerebral arteries

Lombard

Sylvester

Phillips

et al. 2003

American Journal of Physiology-Heart and Circulatory Physiology

132

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. High-salt diet impairs vascular relaxation mechanisms in rat middle cerebral arteries. Am J Physiol Heart Circ Physiol 284: H1124-H1133, 2003. First published November 27, 2002 10.1152/ajpheart.00835. 2002-Male Sprague-Dawley rats were maintained on a low-salt (LS) diet (0.4% NaCl) or a high-salt (HS) diet (4% NaCl) for 3 days or 4 wk. PO2 reduction to 40-45 mmHg, the stable prostacyclin analog iloprost (10 pg/ml), and stimulatory G protein activation with cholera toxin (1 ng/ml) caused vascular smooth muscle (VSM) hyperpolarization, increased cAMP production, and dilation in cerebral arteries from rats on a LS diet. Arteries from rats on a HS diet exhibited VSM depolarization and constriction in response to hypoxia and iloprost, failed to dilate or hyperpolarize in response to cholera toxin, and cAMP production did not increase in response to hypoxia, iloprost, or cholera toxin. Low-dose angiotensin II infusion (5 ng ⅐ kg Ϫ1 ⅐ min Ϫ1 iv) restored normal responses to reduced PO2 and iloprost in arteries from animals on a HS diet. These observations suggest that angiotensin II suppression with a HS diet leads to impaired relaxation of cerebral arteries in response to vasodilator stimuli acting at the cell membrane. salt intake; hypertension; angiotensin; hypoxia; vascular smooth muscle; endothelium PREVIOUS STUDIES (8,11,19) have demonstrated that both chronic (4-8 wk) volume expanded hypertension caused by reduced renal mass (RRM) with exposure to a high-salt diet and chronic exposure of normotensive rats to a high-salt diet lead to structural changes in arterioles, reductions in microvessel density, and an impaired relaxation of skeletal muscle resistance vessels in response to a variety of vasodilator stimuli, including reduced PO 2 , the stable prostacyclin analog iloprost, and acetylcholine. Subsequent studies demonstrated that alterations in microvessel structure, density, and reactivity in normotensive animals and RRM hypertensive rats on a high-salt diet develop quite rapidly. For example, Hansen-Smith et al. (15) demonstrated that microvascular rarefaction and profound ultrastructural alterations occur in arterioles of RRM hypertensive rats and normotensive animals after only 3 days on a high-salt diet. Other studies (10)(11)(12)38) have demonstrated that vasodilator responses to reduced PO 2 , acetylcholine, and iloprost are also impaired after short-term exposure to high-salt diet. The microvascular rarefaction and the reduced relaxation of resistance arteries to vasodilator stimuli in animals on a high-salt diet may be related to the angiotensin II (ANG II) suppression that occurs in response to elevated dietary salt intake because both the reduction of cremasteric microvessel density (16) and the impaired dilation of skeletal muscle resistance arteries in response to acetylcholine, iloprost, and reduced PO 2 in animals on a high-salt diet can be prevented by infusion of a low dose of ANG II (37,38).To date, the majority of studies investigating changes in vascular control mechanisms with a highsa...

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Prostaglandin H Synthase and Vascular Function

Cited by 207 publications

References 165 publications

The Aldo-Keto Reductase Superfamily and its Role in Drug Metabolism and Detoxification

The Aldo-Keto Reductase Superfamily and its Role in Drug Metabolism and Detoxification

Histamine Directly and Synergistically with Lipopolysaccharide Stimulates Cyclooxygenase-2 Expression and Prostaglandin I2 and E2 Production in Human Coronary Artery Endothelial Cells

High-salt diet impairs vascular relaxation mechanisms in rat middle cerebral arteries

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