Expression of functional prostaglandin D (DP) receptors in human corpus cavernosum smooth muscle

Moreland, Robert B.; Nehra, Ajay; Kim, N. N.; Min, Kweon Sik; Albadawi, Hassan; Watkins, Michael T.; Goldstein, Irwin; Traish, Abdulmaged M.

doi:10.1038/sj.ijir.3900900

Cited by 17 publications

(16 citation statements)

References 32 publications

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“…31,32 Higher serum BTP values have been associated with lower serum albumin values and more severe sleep apnea, suggesting a possible link with vascular or endothelial dysfunction. [33][34][35][36] The Mild and Moderate Kidney Disease study examined the association of BTP adjusted for measured GFR with CKD progression in 177 patients (29 kidney failure outcomes).…”

Section: Discussionmentioning

confidence: 99%

Filtration Markers May Have Prognostic Value Independent of Glomerular Filtration Rate

Tangri

Inker

Tighiouart

et al. 2012

Journal of the American Society of Nephrology

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Serum levels of creatinine, cystatin C, or b trace protein allow estimation of GFR, but whether these markers contribute additional prognostic information beyond that reflected in GFR is unknown. Here, we analyzed data from the Modification of Diet in Renal Disease study, which provided baseline levels of these markers for 816 participants with a median follow-up of 16.6 years. We examined associations between the reciprocals of these filtration markers and 125 I iothalamate GFR, expressed per SD, with kidney failure and mortality. In univariate analysis, lower GFR and higher levels of each filtration marker associated with a higher risk for all outcomes. After adjustment for GFR in a Cox proportional hazards model, higher creatinine associated with a higher risk for kidney failure but a lower risk for all-cause mortality. Higher cystatin C and b trace protein associated with a higher risk for both kidney failure and all-cause mortality. In models including either cystatin C or b trace protein, the association of GFR with all-cause mortality was no longer significant after the addition of the filtration marker, suggesting the possibility of multicollinearity. In summary, after adjustment for GFR, levels of creatinine, cystatin C, and b trace protein, each remained directly associated with kidney failure but differed with respect to their associations with mortality. These differences may be a result of non-GFR-related associations of filtration markers, residual confounding by GFR, or collinearity between the filtration markers and GFR. b trace protein and cystatin C seem to provide more consistent prognostic information than creatinine.

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Section: Discussionmentioning

confidence: 99%

Filtration Markers May Have Prognostic Value Independent of Glomerular Filtration Rate

Tangri

Inker

Tighiouart

et al. 2012

Journal of the American Society of Nephrology

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“…11 Because prostaglandin DP receptors have been detected in human corpus cavernosum and are associated with functional dilatory effects on isolated corpus cavernosum smooth muscle in vitro, it is logical that DP-selective agonists have been suggested as possible agents for the treatment of erectile dysfunction. 5 In the present study, the haemodynamic profile of the DP-selective agonist BW245C was examined in anaesthetized rats and regional blood flow responses to intravenous infusion of the agonist were characterised to determine whether a differential response to the compound exists. These data extend previous observations by other investigators, in which BW245C produced a dose-dependent hypotension when administered intravenously in rodents, canines and primates.…”

Section: Discussionmentioning

confidence: 99%

“…3 BW245C has been shown to relax human corpus cavernosum smooth muscle with an EC 50 of 10 nmol/L. 5 Furthermore, the compound is orally bioavailable and has been successfully tested in early phase clinical trials. 8,9 The hypotensive effects of BW245C in experimental models suggest that the compound elicits a systemic vasodilator response; however, it is not known whether the vascular beds of various organ systems are differentially affected.…”

Section: Introductionmentioning

confidence: 99%

“…[3][4][5] The discovery of prostaglandin DP receptors in human corpus cavernosum and the finding that DP agonists relax corpus cavernosum smooth muscle led to the observation that DPselective agonists may be useful as peripherally acting agents to treat erectile dysfunction. 5 The prostanoid agonist BW245C, a potent and selective receptor agonist for the DP receptor subtype, 6 is the most comprehensively studied of the synthetic DP agonists and has been shown to produce hypotension and tachycardia in a dose-dependent manner in the anaesthetized rat. 7 BW245C potently displaces PGD 2 on rat DP receptor in competition binding assays (K i = 15 nmol/L) and is a full agonist at the rat DP receptor (EC 50 = 1.9 nmol/L).…”

Section: Introductionmentioning

confidence: 99%

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Effects of BW245C, a prostaglandin dp receptor agonist, on systemic and regional haemodynamics in the anaesthetized rat

Koch

Wessale

Moreland

et al. 2005

Clin Exp Pharma Physio

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1. Prostaglandin D (DP) receptor agonists have been shown to induce hypotension in rat models, possibly via peripheral vasodilation. However, it is not known which tissues and organs are most responsive. 2. In the present study, BW245C, a DP receptor-selective agonist, was administered to Inactin (Sigma, St Louis, MO, USA)-anaesthetized rats. Animals received three serial i.v. infusions (17 min each) of either BW245C (escalating doses of 0.3, 3 and 30 microg/kg; n=6) or vehicle (6% ethanol in normal saline; n=6). Mean arterial pressure (MAP) and heart rate were monitored continuously and regional blood flow was determined by the radionuclide-labelled microsphere method at baseline and at the end of each infusion. 3. It was found that BW245C dose-dependently reduced MAP; blood flow increased in forelimb skeletal muscle and skin, resulting in decreases in the regional vascular resistance (RVR) of skeletal muscle to -6+/-13, -53+/-11 and -68+/-6% of baseline following 0.3, 3 and 30 microg/kg BW245C, respectively (P<0.05 vs vehicle treatment for the two higher doses), and skin to -29+/-8, -55+/-8 (P<0.05) and -30+/-16% of baseline, respectively. Relative to vehicle, blood flow and RVR for brain, heart, lung, liver, stomach and kidney were not significantly affected by BW245C. 4. These results demonstrate that the hypotension resulting from DP receptor activation in the rat is mediated primarily through vasodilation of arterioles of skeletal muscle independent of changes in blood flow to vital organs.

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“…Because the normal biological activity of NOS depends on oxygen molecules, the biosynthesis of NO is restrained under anaerobic conditions and the vasoconstrictor (norepinephrine, endothelin) is dominant, limiting the diastolic of corpus cavernosum trabecular and resulting in a persistent flaccid state (Kim et al, 1993;Palmer et al, 1994;Christ, 1995;Nehra et al, 1996;Burnett, 1997;Traish et al, 1997;Moreland, 1998;Moreland et al, 2001Moreland et al, , 2002Prieto et al, 2010;Liu et al, 2012). Synthesis of cytokines, growth factors, internal secretion, and vasoactive factors is affected by oxygen partial pressure, and these factors play an important role in the metabolism of smooth muscle cells and connective tissue (Traish, 1997), making the ratio of functional connective tissue/muscle maintained in the normal range to ensure the normal erectile of the penis (Gao et al, 1996;Traish, 1997).…”

Section: Discussionmentioning

confidence: 99%

Effect of chronic hypoxia on penile erectile function in rats

Liu

Wei

2015

Genet. Mol. Res.

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ABSTRACT. We examined the relationship between chronic hypoxia and erectile dysfunction in rat and its possible pathogenic mechanism. Forty-eight white male adult Sprague-Dawley rats were randomly divided into a test group and a control group. In accordance with the experimental time (2, 6, and 10 weeks), each group was divided into 3 subgroups, with 8 rats in each subgroup. Rats in the test group were fed in an airtight hypoxia cabin, while rats in the control group were maintained in a normal environment, with other conditions kept the same. At 2, 6, and 10 weeks, the rats in each group were observed for erectile function. Affinity purification was used to detect neural nitric oxide synthase (nNOS)-positive nerve fibers and endothelial nitric oxide synthase (eNOS) expression. After hypoxia, erectile frequency decreased significantly compared to before hypoxia (P < 0.001).Comparison of the test group and control group revealed a significant difference in the quantity of nNOS-positive nerve fiber and eNOS protein expression (P < 0.01). Hypoxia may influence erectile function 10482-10489 (2015) and nNOS and eNOS expression in rats. The decrease in the quantity of nNOS nerve fibers and expression of eNOS may contribute to erectile dysfunction under hypoxic conditions in rats.

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Expression of functional prostaglandin D (DP) receptors in human corpus cavernosum smooth muscle

Cited by 17 publications

References 32 publications

Filtration Markers May Have Prognostic Value Independent of Glomerular Filtration Rate

Filtration Markers May Have Prognostic Value Independent of Glomerular Filtration Rate

Effects of BW245C, a prostaglandin dp receptor agonist, on systemic and regional haemodynamics in the anaesthetized rat

Effect of chronic hypoxia on penile erectile function in rats

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