Increased renal formation of thromboxane A 2 and prostaglandin F 2α in heart failure

Castellani, Sergio; Paladini, Barbara; Paniccia, Rita; Serio, Claudia Di; Vallotti, Barbara; Ungar, Andrea; Fumagalli, Stefano; Cantini, Claudia; Poggesi, Loredana; Serneri, Gian Gastone Neri

doi:10.1016/s0002-8703(97)70253-9

Cited by 25 publications

(9 citation statements)

References 29 publications

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“…1992 ). This result together with ours may indicate a role of arachidonic acid related metabolites in vascular contractility in CHF especially as the production of TXA 2 in the kidney in humans with CHF is elevated ( Castellani et al . 1997 ).…”

Section: Discussionsupporting

confidence: 73%

Dilatory responses to acetylcholine, calcitonin gene‐related peptide and substance P in the congestive heart failure rat

Bergdahl

Valdemarsson

Nilsson

et al. 1999

Acta Physiologica Scandinavica

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It was examined to what extent congestive heart failure (CHF) in rats, induced by ligation of the left coronary artery, affects the vascular responses to the vasodilatory substances acetylcholine (ACh), calcitonin gene-related peptide (CGRP), and substance P (SP). After induction of CHF status, the basilar, mesenteric and renal arteries and the iliac vein were studied in vitro. Dilatory responses were determined in relation to pre-contraction by the thromboxane mimetic U46619. Sham-operated animals (Sham) served as controls. U46619 induced stronger contraction in CHF basilar and renal arteries compared with the corresponding segments in Sham. ACh induced concentration-dependent dilations in all vessels examined with no difference of maximum relaxation or potency between CHF and Sham. SP induced weak dilations in all arteries examined while the response was markedly attenuated in CHF iliac veins compared with Sham (Emax% 12.2 +/- 3.4 vs. 32.3 +/- 4.8, P = 0.01). The CGRP induced dilation in the CHF basilar artery was weaker (Emax% 18.6 +/- 6.5 vs. 66.9 +/- 5.0, P< 0.001) and less potent (pEC50: 8.2 +/- 0.2 vs. 9.0 +/- 0.2, P = 0.01) compared with Sham. Further, CGRP was less potent in the renal artery of CHF rats compared with Sham (pEC50: 8.1 +/- 0.2 vs. 9.5 +/- 0.3, P < 0.01). In the CHF iliac vein, CGRP was more potent compared with Sham (pEC50: 9.7 +/- 0.4 vs. 8.3 +/- 0.4, P < 0.05). It can be concluded CHF is accompanied by alterations in the vascular response to the dilatory substances studied. The changes differ between vascular beds and between the different substances.

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Section: Discussionsupporting

confidence: 73%

Dilatory responses to acetylcholine, calcitonin gene‐related peptide and substance P in the congestive heart failure rat

Bergdahl

Valdemarsson

Nilsson

et al. 1999

Acta Physiologica Scandinavica

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“…Although PGE 2 is the most prominent prostanoid in various diseases, these other prostanoids (thromboxanes, PGI 2 , PGD 2 , and PGF2 ) may also essentially contribute to distinct pathologies. For example, an exaggerative thromboxane synthesis is associated with cardiovascular diseases including myocardial ischemia [117] and heart failure [118], PGD 2 is predominantly produced by activated mast cells and essentially contributes to allergic responses [119], and PGF2 was found to induce allodynia [120] and to mediate lipopolysaccharide-induced tachycardia in mice [121]. On the other hand, the redirection of prostanoids upon blockade of mPGES-1 is not necessarily detrimental because some of them (i.e., PGI 2 , PGF2 , PGD 2 ) also show partially anti-inflammatory and cytoprotective effects [122].…”

Section: Is Mpges-1 a Potential Anti-inflammatory Target?mentioning

confidence: 99%

Inhibitors of the Microsomal Prostaglandin E2 Synthase-1 as Alternative to Non Steroidal Anti-Inflammatory Drugs (NSAIDs) – A Critical Review

Koeberle¹,

Werz

2009

CMC

112

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Pharmacological suppression of cyclooxygenase (COX)-1 and -2-mediated prostanoid biosynthesis by non steroidal anti-inflammatory drugs (NSAIDs) is used in the therapy of inflammation, fever, and pain. However, long-term application of these drugs is associated with severe side effects, mainly gastrointestinal injury and renal irritations, apparently due to impaired biosynthesis of physiologically relevant prostanoids. Although COX-2 selective drugs (coxibs) show reduced gastrointestinal complications, recent clinical trials indicated a significantly increased cardiovascular risk. In order to minimize these side-effects, selective suppression of microsomal prostaglandin E(2) synthase (mPGES)-1 derived prostaglandin (PG)E(2) formation has been considered as alternative to general inhibition of prostanoid biosynthesis. mPGES-1 is functionally coupled to COX-2 being responsible for excessive PGE(2) generation connected to pathologies and current knowledge suggests key roles of mPGES-1 in inflammation, pain, fever, atherosclerosis, and tumorigenesis. However, mPGES-1 as promising therapeutic target was questioned because blockade of mPGES-1 allows redirection of the substrate PGH(2) to other PG synthases, and the consequences are still elusive. This review summarizes current knowledge about synthetic and natural mPGES-1 inhibitors focusing on structural and mechanistic investigations. Further, the therapeutic efficiency and safety is critically discussed on the basis of cellular and animal studies in which mPGES-1 activity was pharmacologically or genetically (knockout, knockdown) modulated.

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“…Enhanced thromboxane synthesis has been linked to cardiovascular diseases including acute myocardial ischemia [58], heart failure [59] and diabetes [60] in clinic. In contrast, the depressed TP receptor-mediated responsiveness in the aortic segments has been observed in streptozotocin-induced diabetic rats, while insulin therapy reversed the decreased contractile responses [13].…”

Section: Discussionmentioning

confidence: 99%

Transcriptional Down-Regulation of Thromboxane A<sub>2</sub> Receptor Expression via Activation of MAPK ERK1/2, p38/NF-κB Pathways

Zhang¹,

Zhang

Edvinsson

et al. 2008

J Vasc Res

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Background: We have developed an in vitro model by organ culture of rat mesenteric arteries to imitate vascular smooth muscle cell (VSMC) receptor changes in cardiovascular disease. By using this model, alteration of VSMC thromboxane A₂ (TP) receptors was studied. Methods and Results:After organ culture of the arteries, VSMC TP receptors were studied by using myography, real-time PCR and immunohistochemistry. We observed that organ culture for 24 and 48 h resulted in depressed TP receptor-mediated contraction in the VSMC, in parallel with decreased TP receptor mRNA and protein expressions. Phosphorylation of extracellular signal-regulated kinase 1 and 2 (ERK1/2), p38 and nuclear factor-κB (NF-κB) was seen by Western blot within 1–3 h after organ culture. Inhibition of ERK1/2, p38 or NF-κB reversed depressed contraction as well as decreased receptor mRNA expression. Actinomycin D abolished decreased TP receptor-mediated contraction, while inhibition of translation, cyclooxygenase or nitric oxide synthase had no effect. TP receptor mRNA stability was unchanged during organ culture. Conclusions:The present study has demonstrated for the first time that organ culture of rat mesenteric arteries down-regulates VSMC TP receptor expression through activation of ERK1/2 and p38/NF-κB signal pathways.

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Increased renal formation of thromboxane A 2 and prostaglandin F 2α in heart failure

Cited by 25 publications

References 29 publications

Dilatory responses to acetylcholine, calcitonin gene‐related peptide and substance P in the congestive heart failure rat

Dilatory responses to acetylcholine, calcitonin gene‐related peptide and substance P in the congestive heart failure rat

Inhibitors of the Microsomal Prostaglandin E2 Synthase-1 as Alternative to Non Steroidal Anti-Inflammatory Drugs (NSAIDs) – A Critical Review

Transcriptional Down-Regulation of Thromboxane A<sub>2</sub> Receptor Expression via Activation of MAPK ERK1/2, p38/NF-κB Pathways

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