Orchidectomy increases the formation of prostanoids and modulates their role in the acetylcholine-induced relaxation in the rat aorta

Martorell, Aina; Blanco-Rivero, Javier; Aras-López, Rosa; Sagredo, Ana; Balfagón, Gloria; Ferrer, Mercedes

doi:10.1093/cvr/cvm059

Cited by 26 publications

(33 citation statements)

References 54 publications

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“…We previously reported that, in mesenteric artery from comparable rats, endogenous male sex hormones modulate endothelial TXA 2 production, whether in basal conditions or after stimulation with either clonidine (Blanco-Rivero et al 2006a) or acetylcholine (Blanco-Rivero et al 2007), without modifying the TXA 2 vasoconstrictor effect. Additionally, we have also shown that endogenous male sex hormones regulate the functional involvement of endogenous TXA 2 in vascular responses of aorta (Martorell et al 2008) and mesenteric artery (Blanco-Rivero et al 2006a.…”

Section: Introductionmentioning

confidence: 66%

“…We previously reported that endothelial TXA 2 release in mesenteric artery (Blanco-Rivero et al 2006a and aorta (Martorell et al 2008) was increased in arteries from orchidectomized rats. The fact that the levels of testosterone dramatically decreased in orchidectomized rats (Martorell et al 2008) seems to indicate that the vascular effects observed are testosterone dependent. However, the involvement of hormones and/or gonadal factors other than testosterone cannot be ruled out.…”

Section: Discussionmentioning

confidence: 95%

“…TXA 2 is one of the most important vasoconstrictor prostanoids with stimulatory action on proliferation or hypertrophy of vascular smooth muscle cells (Hanasaki et al 1990), and is implicated as a mediator in diseases such as myocardial infarction, hypertension, and stroke (FitzGerald et al 1987, Narumiya et al 1999. We previously reported that endothelial TXA 2 release in mesenteric artery (Blanco-Rivero et al 2006a and aorta (Martorell et al 2008) was increased in arteries from orchidectomized rats. The fact that the levels of testosterone dramatically decreased in orchidectomized rats (Martorell et al 2008) seems to indicate that the vascular effects observed are testosterone dependent.…”

Section: Discussionmentioning

confidence: 99%

“…Recent studies have reported beneficial effects of androgens in cardiovascular function in males through different mechanisms that involve NO and prostanoids (Jones et al 2004, Martorell et al 2008. The activation of androgen receptors, expressed in both the endothelial (Yu et al 2007) and smooth muscle (Ma et al 2005) cells, regulates cell signaling pathways.…”

Section: Discussionmentioning

confidence: 99%

“…One of the more plausible candidates would be PGI 2 , since crosstalk between TXA 2 and PGI 2 systems has been reported (Cheng et al 2002, Martorell et al 2008 and joint increases in PGI 2 and TXA 2 synthesis have been shown in pathological conditions (FitzGerald 1991, Caughey et al 2001. Therefore, we measured the production of PGI 2 in the presence of furegrelate in mesenteric arteries from both control and orchidectomized rats.…”

Section: Discussionmentioning

confidence: 99%

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Orchidectomy increases the formation of non-endothelial thromboxane A2 and modulates its role in the electrical field stimulation-induced response in rat mesenteric artery

Campo¹,

Sagredo²,

Aras-López³

et al. 2008

Journal of Endocrinology

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The aim of this study was to analyze whether endogenous male sex hormones influence the release of thromboxane A 2 (TXA 2 ) and its role in the electrical field stimulation (EFS)-induced response, as well as the mechanism involved. For this purpose, endothelium-denuded mesenteric arteries from control and orchidectomized male Sprague-Dawley rats were used to measure TXA 2 release; EFS-induced response, nitric oxide (NO), norepinephrine (NA), and prostaglandin (PG) I 2 release were also measured in the presence of the TXA 2 synthesis inhibitor furegrelate. Orchidectomy increased basal and EFS-induced TXA 2 release. Furegrelate decreased the EFS-induced contraction in arteries from control rats, but did not modify it in arteries from orchidectomized rats. The EFS-induced neuronal NO release and vasodilator response were increased by furegrelate in arteries from control rats, but were not modified in arteries from orchidectomized rats. Furegrelate did not modify the EFS-induced NA release or vasoconstrictor response in arteries from either control or orchidectomized rats. The EFS-induced PGI 2 release was not modified by furegrelate in arteries from control rats, but was increased in arteries from orchidectomized rats. The results of the present study show that endogenous male sex hormone deprivation i) increases non-endothelial TXA 2 release and ii) regulates the effect of endogenous TXA 2 on the EFS-induced response through different mechanisms that, at the least, involve the NO and PGI 2 systems. In arteries from control rats, inhibition of TXA 2 formation decreases the EFS-induced response by increasing neuronal NO release. In arteries from orchidectomized rats, the EFS-induced response is unaltered after the inhibition of TXA 2 formation, by increasing PGI 2 release.

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Section: Introductionmentioning

confidence: 66%

Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 3 more Smart Citations

Orchidectomy increases the formation of non-endothelial thromboxane A2 and modulates its role in the electrical field stimulation-induced response in rat mesenteric artery

Campo¹,

Sagredo²,

Aras-López³

et al. 2008

Journal of Endocrinology

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Conjugated Linoleic Acid Supplemented Diet Influences Serum Markers in Orchidectomized Sprague‐Dawley Rats

Rojas

Villalpando

Ferrer

et al. 2020

Euro J Lipid Sci & Tech

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Conjugated isomers of linoleic acid have beneficial effects on human health, with demonstrated anticarcinogenic, antiatherogenic, antioxidant, and anti‐inflammatory properties. Previous studies have shown that the loss of sex hormones induced by orchidectomy affects vascular function and serum lipids. The objective of this work is to evaluate the effect of conjugated linoleic acid (CLA) on serum lipids, cardiac, renal, and hepatic markers in orchidectomized Sprague‐Dawley rats. Male sex hormone deprivation is induced by orchidectomy to 24‐week‐old rats. The rats are fed a diet containing 1.8% w/w CLA, or a control diet for 8 weeks. At the end of the treatment, serum markers are measured using commercially available kits. The concentrations found in the orchidectomized‐CLA (ORX‐CLA) group of total cholesterol, low‐density lipoproteins (LDL), as well as the atherogenic index, concentrations of creatine kinase, lactate dehydrogenase, C‐reactive protein, glucose, urea, uric acid, creatinine, albumin, calcium, total protein, and bilirubin are significantly lower compared to the orchidectomized‐control (ORX‐C) group. The concentrations of high‐density lipoproteins (HDL), calcium, total protein, albumin, total bilirubin, and indirect bilirubin are significantly higher in the ORX‐CLA group than in the ORX‐C group. The CLA‐supplemented diet exerts a beneficial effect on different biochemical parameters negatively affected by orchidectomy, which may result in vascular protection. Practical Applications: The relationship between testosterone deficiency and the alteration of serum lipids is demonstrated; however, it is demonstrated in this study that the markers of renal damage, cardiac damage, and oxidative stress are also negatively affected by the lack of this hormone. This information has enriched the understanding about the relationship between testosterone deficiency and the development of different diseases such as metabolic syndrome, type 2 diabetes, kidney failure, osteoporosis, cardiovascular diseases, and cancer. On the other hand, CLA has been studied mainly as a nutraceutical and sports supplement; the information in this study will help to expand the knowledge about the benefits of these isomers of linoleic acid, providing guidelines for its use as a protection against negative effects triggered by orchidectomy.

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Endothelial dysfunction after androgen deprivation therapy and the possible underlying mechanisms

et al. 2021

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Introduction: Androgen deprivation therapy (ADT) is a key treatment modality in the management of prostate cancer (PCa), especially for patients with metastatic disease. Increasing evidences suggest that patients who received ADT have increased incidence of diabetes, myocardial infarction, stroke, and even mortality. It is important to understand the pathophysiological mechanisms on how ADT increases cardiovascular risk and induces cardiovascular events, which would provide important information for potential implementation of preventive measures.Methods: Twenty-six 12-week-old male SD rats were divided into four groups for different types of ADTs including: the bilateral orchidectomy group (Orx), LHRH agonist group (leuprolide), LHRH antagonist group (degarelix), and control group.After treated with drug or adjuvant injection every 3 weeks for 24 weeks, all rats were sacrificed and total blood were collected. Aorta, renal arteries, and kidney were preserved for functional assay, immunohistochemistry, western blot, and quantitative reverse-transcription polymerase chain reaction.Results: In vascular reactivity assays, aorta, intrarenal, and coronary arteries of all three ADT groups showed endothelial dysfunction. AT1R and related molecules at protein and messenger RNA (mRNA) level were tested, and AT1R pathway was shown to be activated and played a role in endothelial dysfunction. Both ACE and AT1R mRNA levels were doubled in the aorta in the leuprolide group while Orx and degarelix groups showed upregulation of AT1R in the kidney tissues. By immunohistochemistry, our result showed higher expression of AT1R in the intrarenal arteries of leuprolide and degarelix groups. The role of reactive oxygen species in endothelial dysfunction was confirmed by DHE fluorescence, nitrotyrosine overexpression, and upregulation of NOX2 in the different ADT treatment groups. Conclusion:ADT causes endothelial dysfunction in male rats. GnRH receptor agonist compared to GnRH receptor antagonist, showed more impairment of endothelial function in the aorta and intrarenal arteries. Such change might be associated with upregulation and activation of AngII-AT1R-NOX2 induced oxidative stress in the

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Orchidectomy increases the formation of prostanoids and modulates their role in the acetylcholine-induced relaxation in the rat aorta

Cited by 26 publications

References 54 publications

Orchidectomy increases the formation of non-endothelial thromboxane A2 and modulates its role in the electrical field stimulation-induced response in rat mesenteric artery

Orchidectomy increases the formation of non-endothelial thromboxane A2 and modulates its role in the electrical field stimulation-induced response in rat mesenteric artery

Conjugated Linoleic Acid Supplemented Diet Influences Serum Markers in Orchidectomized Sprague‐Dawley Rats

Endothelial dysfunction after androgen deprivation therapy and the possible underlying mechanisms

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