Thromboxane A2 receptor antagonists inhibit endothelium-dependent contractions.

Auch-Schwelk, Wolfgang; Katušić, Zvonimir S.; Vanhoutte, Paul M.

doi:10.1161/01.hyp.15.6.699

Cited by 193 publications

(141 citation statements)

References 21 publications

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“…Previous studies by our group (7,20) have indicated that endothelium-derived cyclooxygenase (COX) metabolites, most likely prostacyclin, mediate hypoxic dilation in response to reduced PO 2 in rat MCA. Several other studies (1,28,34) have suggested that a COX product, most likely prostaglandin H 2 (PGH2) or thromboxane A2 (TxA2), acts as a constrictor factor in several forms of hypertension. To evaluate the role of COX metabolites in mediating the response of the vessels to reduced PO 2 in animals on high-and low-salt diets, vessel diameters were measured before and during inhibition of cyclooxygenase with 1 M indomethacin.…”

Section: Methodsmentioning

confidence: 99%

“…Previous studies have suggested that overproduction of vasoconstrictor factors, such as PGH 2 and TxA 2 via cyclooxygenases, can contribute to an impaired relaxation in response to endotheliumdependent vasodilator stimuli in spontaneously hypertensive rats (1,28) and spontaneously hypertensive hamsters (34). The results of the present study suggest that TxA 2 plays a role in mediating the paradoxical constriction in response to reduced PO 2 in MCA of animals on a high-salt diet because TxA 2 production was significantly elevated during resting conditions in vessels from rats on high-salt diet and TxA 2 release tended to increase during hypoxia in vessels from animals on high-salt diet.…”

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

confidence: 99%

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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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Section: Methodsmentioning

confidence: 99%

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

View full text Add to dashboard Cite

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“…This contracting factor is derived from endothelial cyclooxygenase and activates thromboxane prostanoid receptors of vascular smooth muscle (Lüscher and Vanhoutte, 1986;Auch-Schwelk et al, 1990;Yang et al, 2004b;Vanhoutte et al, 2005). Endothelium-and cyclooxygenase-dependent contractions are prominent in the aorta of the spontaneously hypertensive rat (Lüscher and Vanhoutte, 1986;Yang et al, 2004a, b;Tang et al, 2007), the abdominal aorta of the diabetic rabbit and the femoral artery of the diabetic rat (Shi et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

“…Endothelium-and cyclooxygenase-dependent contractions are prominent in the aorta of the spontaneously hypertensive rat (Lüscher and Vanhoutte, 1986;Yang et al, 2004a, b;Tang et al, 2007), the abdominal aorta of the diabetic rabbit and the femoral artery of the diabetic rat (Shi et al, 2007). The endothelium-derived contracting factor can be prostacyclin, thromboxane A 2 , endoperoxides, prostaglandin E 2 , hydroxyl radicals or superoxide anions depending on the animal model, the preparation and the agonist used Auch-Schwelk et al, 1990;Yang et al, 2004a, b;Gluais et al, 2005Gluais et al, , 2006Shi et al, 2007). Oxygen-derived free radicals facilitate endothelium-dependent contractions, and antioxidants effectively decreased them in the aorta of spontaneously hypertensive rats Yang et al, 2002Yang et al, , 2003bTang et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

Oxygen‐derived free radicals mediate endothelium‐dependent contractions in femoral arteries of rats with streptozotocin‐induced diabetes

Shi

Man

et al. 2007

British J Pharmacology

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Background and purpose:The present experiments were designed to study the contribution of oxygen-derived free radicals to endothelium-dependent contractions in femoral arteries of rats with streptozotocin-induced diabetes. Experimental approach: Rings with and without endothelium were suspended in organ chambers for isometric tension recording. The production of oxygen-derived free radicals in the endothelium was measured with 2 0 ,7 0 -dichlorodihydrofluorescein diacetate using confocal microscopy. The presence of protein was measured by western blotting. Key results: In the presence of L-NAME, the calcium ionophore A23187 induced larger endothelium-dependent contractions in femoral arteries from diabetic rats. Tiron, catalase, deferoxamine and MnTMPyP, but not superoxide dismutase reduced the response, suggesting that oxygen-derived free radicals are involved in the endothelium-dependent contraction. In the presence of L-NAME, A23187 increased the fluorescence signal in femoral arteries from streptozotocin-treated, but not in those from control rats, confirming that the production of oxygen-derived free radicals contributes to the enhanced endotheliumdependent contractions in diabetes. Exogenous H 2 O 2 caused contractions in femoral arterial rings without endothelium which were reduced by deferoxamine, indicating that hydroxyl radicals contract vascular smooth muscle and thus could be an endothelium-derived contracting factor in diabetes. The reduced presence of Mn-SOD and the decreased activity of catalase in femoral arteries from streptozotocin-treated rats demonstrated the presence of a redox abnormality in arteries from rats with diabetes. Conclusions and implications: These findings suggest that the redox abnormality resulting from diabetes increases oxidative stress which facilitates and/or causes endothelium-dependent contractions.

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“…1 -3 - 5 The purpose of the present study was to determine whether endothelium-dependent contrac-tions to acetylcholine are modified by the simultaneous release of endothelium-derived relaxing factor.…”

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confidence: 99%

Nitric oxide inactivates endothelium-derived contracting factor in the rat aorta.

1992

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Acetylcholine evokes the simultaneous release of endothelium-derived relaxing and contracting factors in aortas from spontaneously hypertensive rats. Only relaxing factors are released in aortas from normotensive controls. Experiments were designed to determine whether inhibitors of endotheliumdependent relaxations modify endothelium-dependent contractions. Rings of thoracic aortas of normotensive and spontaneously hypertensive rats, with and without endothelium, were suspended in organ chambers for isometric tension recording. Oxyhemoglobin (a scavenger of endothelium-derived relaxing factor) and jV G -monomethyl L-arginine (an inhibitor of nitric oxide formation) augmented the contractions to acetylcholine. Methylene blue (an inhibitor of soluble guanylate cyclase) and superoxide dismutase (a scavenger of superoxide anions) did not modify these contractions. The contractions in the presence of oxyhemoglobin or JV G -monomethyl L-arginine, like those in untreated rings, were endothelium-dependent; they only occurred in aortas from spontaneously hypertensive rats and were abolished by indomethacin. The contractions to acetylcholine in the presence of oxyhemoglobin were not affected by superoxide dismutase or deferoxamine. These data suggest that endothelium-derived relaxing factor inhibits endothelium-dependent contractions to acetylcholine in the spontaneously hypertensive rat aorta, probably by chemical inactivation of the endothelium-derived contracting factor rather than by stimulation of guanylate cyclase or scavenging of oxygen-derived free radicals. A cetylcholine causes the simultaneous release of / \ endothelium-derived relaxing and contracting A. V . factors in aortas from spontaneously hypertensive rats (SHR).1 -2 Only relaxing factors are released from normotensive controls, Wistar-Kyoto (WKY) rats. -2 In rings contracted with norepinephrine, the concomitant release of endothelium-derived contracting factor from SHR aortas leads to reduced endothelium-dependent relaxations compared with aortas from WKY rats.1 In quiescent rings, acetylcholine causes endothelium-dependent contractions only in aortas from SHR but not from WKY rats.1 The nature of the contracting factors has not been identified so far. It appears to be an unstable product of cyclooxygenase (most likely endoperoxides) that stimulates thromboxane A 2 /prostaglandin H 2 receptors on vascular smooth muscle.1 -3 -5 The purpose of the present study was to determine whether endothelium-dependent contrac- tions to acetylcholine are modified by the simultaneous release of endothelium-derived relaxing factor. MethodsThe experiments were performed on the thoracic aorta from male, normotensive WKY rats and age-and weight-matched SHR (30-34 weeks old; weight, WKY 381 + 7 g, n=5, SHR 391+4 g, n = 16) (Harlan Sprague Dawley, Indianapolis, Ind.). Systolic blood pressure was determined by an indirect tail-cuff method in the unanesthetized animal before the experiment (WKY 122±8 mm Hg, SHR 202+4 mm Hg; p<0.05). The thoracic aorta was excised under anest...

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Thromboxane A2 receptor antagonists inhibit endothelium-dependent contractions.

Cited by 193 publications

References 21 publications

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

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

Oxygen‐derived free radicals mediate endothelium‐dependent contractions in femoral arteries of rats with streptozotocin‐induced diabetes

Nitric oxide inactivates endothelium-derived contracting factor in the rat aorta.

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