Reactive oxygen species mediate arachidonic acid-induced dilation in porcine coronary microvessels

Oltman, Christine L.; Kane, Neal L.; Miller, Francis J.; Spector, Arthur A.; Weintraub, Neal L.; Dellsperger, Kevin C.

doi:10.1152/ajpheart.00456.2003

Cited by 46 publications

(33 citation statements)

References 21 publications

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“…AA-mediated vasorelaxation also shows diverse species-and vascular bed-dependent schemes. In human coronary arterioles, the AA effects are mediated via the CYP epoxygenase pathway (31), while AA-induced vasorelaxation in porcine coronary vessels is COX dependent (32). In rat small mesenteric arteries, the AA effects are mainly contributed by 12-HETE, a product of LOX (33), and this pathway is also impaired in ZDF rats (24).…”

Section: Discussionmentioning

confidence: 99%

Impaired Arachidonic Acid–Mediated Activation of Large-Conductance Ca2+-Activated K+ Channels in Coronary Arterial Smooth Muscle Cells in Zucker Diabetic Fatty Rats

Lü

Wang

et al. 2005

Diabetes

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We studied the arachidonic acid (AA)-mediated modulation of large-conductance Ca 2؉ -activated K ؉ (BK) channels in coronary arterial smooth myocytes from lean control and Zucker Diabetic Fatty (ZDF) rats. A total of 1 mol/l AA enhanced BK current by 274% in lean and by 98% in ZDF rats. After incubation with 10 mol/l indomethacin, 1 mol/l AA increased BK currents by 80% in lean and by 70% in ZDF rats. Vasoreactivity studies showed that the dilation of small coronary arteries produced by 1 mol/l AA was reduced by 44% in ZDF rats. . BK channel activation and vasorelaxation by iloprost were similar in lean and ZDF rats. Immunoblots showed a 73% reduction in PGI 2 synthase (PGIS) expression in ZDF vessels compared with lean vessels, and there was no change in cyclooxygenase (COX) and BK channel expressions. Real-time PCR studies showed that mRNA levels of PGIS, COX-1, and COX-2 were similar between lean and ZDF vessels. We conclude that PGI 2 is the major AA metabolite in lean coronaries, and AA-mediated BK channel activation is impaired in ZDF coronaries due to reduced PGIS activity.

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Section: Discussionmentioning

confidence: 99%

Impaired Arachidonic Acid–Mediated Activation of Large-Conductance Ca2+-Activated K+ Channels in Coronary Arterial Smooth Muscle Cells in Zucker Diabetic Fatty Rats

Lü

Wang

et al. 2005

Diabetes

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“…Beyond eNOS, the physiologically complex coronary artery endothelial cells use a number of interrelated vasodilatory pathways. Most notably, prostaglandin E 2 and hydrogen peroxide have recently been shown to play major roles in the regulation of porcine coronary arteriole tone (14,21).…”

Section: Discussionmentioning

confidence: 99%

Newborn lamb coronary artery reactivity is programmed by early gestation dexamethasone before the onset of systemic hypertension

Roghair¹,

Segar

Sharma

et al. 2005

American Journal of Physiology-Regulatory, Integrative and Comp

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. Newborn lamb coronary artery reactivity is programmed by early gestation dexamethasone before the onset of systemic hypertension. Am J Physiol Regul Integr Comp Physiol 289: R1169 -R1176, 2006. First published June 16, 2005 doi:10.1152/ajpregu.00369.2005.-Exposure of the early gestation ovine fetus to exogenous glucocorticoids induces organ-specific alterations in postnatal cardiovascular physiology. To determine whether early gestation corticosteroid exposure alters coronary reactivity before the development of systemic hypertension, dexamethasone (0.28 mg ⅐ kg Ϫ1 ⅐ day Ϫ1 ) was administered to pregnant ewes by intravenous infusion over 48 h beginning at 27 days gestation (term, 145 days). Vascular responsiveness was assessed in endotheliumintact coronary arteries isolated from 1-wk-old steroid-exposed and age-matched control lambs (N ϭ 6). Calcium imaging was performed in fura 2-loaded primary cultures of vascular smooth muscle cells (VSMC) from the harvested coronary arteries. Early gestation steroid exposure did not significantly alter mean arterial blood pressure or coronary reactivity to KCl, thromboxane A 2 mimetic U-46619, or ANG II. Steroid exposure significantly increased coronary artery vasoconstriction to acetylcholine and endothelin-1. Vasodilatation to adenosine, but not nitroprusside or forskolin, was significantly attenuated following early gestation steroid exposure. Endothelin-1 or U-46619 stimulation resulted in a comparable increase in intracellular calcium concentration ([Ca 2ϩ ]i) in coronary VSMC isolated from either dexamethasone-treated or control animals. However, the ANG II-or KCl-mediated increase in [Ca 2ϩ ]i in control VSMC was significantly attenuated in VSMC harvested from dexamethasone-treated lambs. Coronary expression of muscle voltage-gated L-type calcium channel ␣-1 subunit protein was not significantly altered by steroid exposure, whereas endothelial nitric oxide synthase expression was attenuated. These findings demonstrate that early gestation glucocorticoid exposure elicits primary alterations in coronary responsiveness before the development of systemic hypertension. Glucocorticoidinduced alterations in coronary physiology may provide a mechanistic link between an adverse intrauterine environment and later cardiovascular disease. calcium imaging; endothelium; endothelial nitric oxide synthase; fetal programming EXPOSURE OF THE EARLY GESTATION ovine fetus to exogenous glucocorticoids induces organ-specific changes in postnatal cardiovascular physiology. The hypertensive aspect of this model of fetal programming was first described by Dodic et al. in 1998 (3). In their studies, the offspring of ewes given dexamethasone for 48 h beginning at 27 days gestation (term, 145-150 days) were hypertensive at 4 mo of age and remained hypertensive at 10 and 18 mo of age, despite normal intrauterine and postnatal growth. Using an identical model, we recently reproduced the hypertensive phenotype and demonstrated unique alterations in coronary artery reactivity (17). More speci...

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“…Unlike COX-1, which is constitutively expressed, COX-2 is an inducible enzyme with low or undetectable levels under normal conditions. COX-2 is induced under conditions of chronic hypoxia and inflammation, resulting in a greater production of PGE 2 , a vasodilator prostanoid (33,34).…”

Section: Figurementioning

confidence: 99%

Effect of fetal hemoglobin on microvascular regulation in sickle transgenic-knockout mice

Kaul¹,

Liu²,

Chang³

et al. 2004

J. Clin. Invest.

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In sickle cell disease, intravascular sickling and attendant flow abnormalities underlie the chronic inflammation and vascular endothelial abnormalities. However, the relationship between sickling and vascular tone is not well understood. We hypothesized that sickling-induced vaso-occlusive events and attendant oxidative stress will affect microvascular regulatory mechanisms. In the present studies, we have examined whether microvascular abnormalities expressed in sickle transgenic-knockout Berkeley (BERK) mice (which express exclusively human α-and β S -globins with <1% γ-globin levels) are amenable to correction with increased levels of antisickling fetal hemoglobin (HbF). In BERK mice, sickling, increased oxidative stress, and hemolytic anemia are accompanied by vasodilation, compensatory increases in eNOS and COX-2, and attenuated vascular responses to NO-mediated vasoactive stimuli and norepinephrine. The hypotension and vasodilation (required for adequate oxygen delivery in the face of chronic anemia) are mediated by non-NO vasodilators (i.e., prostacyclin) as evidenced by induction of COX-2. In BERK mice, the resistance to NO-mediated vasodilators is associated with increased oxidative stress and hemolytic rate, and in BERK + γ mice (expressing 20% HbF), an improved response to these stimuli is associated with reduced oxidative stress and hemolytic rate. Furthermore, BERK + γ mice show normalization of vessel diameters, and eNOS and COX-2 expression. These results demonstrate a strong relationship between sickling and microvascular function in sickle cell disease.

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Reactive oxygen species mediate arachidonic acid-induced dilation in porcine coronary microvessels

Cited by 46 publications

References 21 publications

Impaired Arachidonic Acid–Mediated Activation of Large-Conductance Ca2+-Activated K+ Channels in Coronary Arterial Smooth Muscle Cells in Zucker Diabetic Fatty Rats

Impaired Arachidonic Acid–Mediated Activation of Large-Conductance Ca2+-Activated K+ Channels in Coronary Arterial Smooth Muscle Cells in Zucker Diabetic Fatty Rats

Newborn lamb coronary artery reactivity is programmed by early gestation dexamethasone before the onset of systemic hypertension

Effect of fetal hemoglobin on microvascular regulation in sickle transgenic-knockout mice

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