Asymmetric dimethyl arginine levels correlate with cardiovascular risk factors in patients with erectile dysfunction

Wierzbicki, Anthony S.; Solomon, Hemant; Lumb, P J; Lyttle, Kereese; Lambert-Hammill, Michelle; Jackson, Graham

doi:10.1016/j.atherosclerosis.2005.06.025

Cited by 33 publications

(28 citation statements)

References 32 publications

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“…12,13 Elevated plasma ADMA reduces systemic NO bioactivity, leading to systemic as well as coronary endothelial dysfunction in patients with ED. 20 On the basis of human data, it is reasonable to speculate that the elevated plasma ADMA levels interfere with the erectile response due to systemic endothelial dysfunction.…”

Section: Ddah In Rat Penile Tissue K Park Et Almentioning

confidence: 99%

“…Several lines of evidence have suggested the potential relationship between ADMA and ED, especially in patients with CADs. 12,13 Intracavernosal injection of ADMA inhibits the pressor responses to pelvic nerve stimulation in the corpus cavernosum of anesthetized dogs, and the inhibitory effect is reversed by L-arginine. 14 Moreover, cavernosal accumulation of ADMA was observed in a rabbit model of cavernosal ischemia, which mimicked the ED observed in AS.…”

Section: Introductionmentioning

confidence: 99%

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Dimethylarginine dimethylaminohydrolase in rat penile tissue: reduced enzyme activity is responsible for erectile dysfunction in a rat model of atherosclerosis

Park¹,

Lee²,

et al. 2009

Int J Impot Res

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Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase (NOS), is mainly metabolized by N G ,N G -dimethylarginine dimethylaminohydrolase (DDAH). We investigated whether altered cavernosal ADMA-DDAH metabolism might cause impairment of erection in rat model of atherosclerosis (AS). Male Sprague-Dawley rats (3 months old) were divided into an AS group and a normal control (Con) group (n ¼ 20 in each group). The AS rats received AS-prone treatment (6 weeks of 1% cholesterol diet plus early 2 weeks of N G -nitro-L-arginine methyl ester (3 mg ml À1 per day) treatment). After 6 weeks, rats underwent cavernosometry measuring the maximal intracavernosal pressure/mean arterial pressure (ICP/MAP) ratios as a surrogate marker of erectile function. The amount of cavernosal ADMA was assessed by immunoblot analysis and correlated with the ICP/MAP. Isoform-specific DDAH expression was compared by immunohistochemistry. Cavernosal DDAH and NOS activity were measured. Cavernosal malondialdehyde levels were assayed to determine the degree of lipid peroxidation. Compared to the controls, the AS rats had signs of impaired erectile function. Higher cavernosal ADMA was observed in the AS rats. The cavernosal ADMA had a moderately negative correlation with the ICP/MAP. Immunohistochemistry revealed the expression of both isoforms was not affected by the presence of AS. However, significantly diminished DDAH as well as NOS activity was observed in the AS group. In addition, elevated cavernosal malondialdehyde levels were noted in the AS rats. Our study showed that decreased cavernosal DDAH activity is the cause of cavernosal ADMA accumulation leading to reduced cavernosal NOS activity and impairment of erectile function.

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Section: Ddah In Rat Penile Tissue K Park Et Almentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Dimethylarginine dimethylaminohydrolase in rat penile tissue: reduced enzyme activity is responsible for erectile dysfunction in a rat model of atherosclerosis

Park¹,

Lee²,

et al. 2009

Int J Impot Res

View full text Add to dashboard Cite

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“…33 Endothelial dysfunction is also a feature of erectile dysfunction and here again aggressive cardiovascular risk factor control seems to be associated with the efficacy of drugs acting on the nitric oxide metabolic pathway (phosphodiesterase-5 inhibitors) and also their effects on pulse wave velocity. 34,35 Similarly, the study investigating the effect of atorvastatin of 80 mg and a 50% LDL-C reduction on pulse wave parameters and blood pressure showed large effects on blood pressure, whereas lesser effects were seen in other studies where LDL-C reductions were smaller and final LDL-C values higher. 36,37 Therefore, the lack of effect of pravastatin on blood pressure in CARE could reflect the inability of this agent to normalise endothelial function in a group of patients with established atherosclerosis, a significant proportion with diabetes and a moderate level of achieved LDL-C in contrast to a primary prevention populations with lower final LDL-C.…”

Section: -12mentioning

confidence: 97%

Statins and hypertension

Wierzbicki

2006

J Hum Hypertens

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Statins (2-hydroxy-methy-glutaryl-CoA enzyme inhibitors) are well-established therapies for coronary heart disease. A large number of studies, grouped into a pre-specified meta-analysis, have shown a reduction of 20-22% in coronary events per 1 mmol/l reduction in LDL-cholesterol (LDL-C).1 However, in contrast to previous studies of other lipid-lowering agents in 450 000 patients, which showed no benefit of cholesterol reduction on stroke, 2 statins have shown a consistent 20-25% reduction in stroke or transient ischaemic effects.3 Only the PROSPER trial failed to show any effect of statins on the pre-specified end point of stroke (relative risk (RR) 1.03, confidence interval (CI) 0.81-1.31) but did show a 20 (CI 0-45)% reduction in transient ischaemic attacks. 4 Notably, this trial showed the poorest degree of control of blood pressure with an average blood pressure of 155/84 mm Hg in contrast to other statin trials where blood pressure was controlled to o140/80 mm Hg.

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“…ADMA remains a strong and independent predictor for CAD in patients with ED, even after adjusting for the usual CV risk factors [65]. Because the PDE-5 inhibitors do not appear to restore normal plasma levels of ADMA [66], it is theoretically possible that the efficacy of these agents could be enhanced by the administration of L-arginine. On the strength of the pre-clinical studies and clinical investigations, there is a strong scientific foundation for clinical trials to assess L-arginine supplementation as a method to improve NO signaling in cardiovascular disease, and its utility in promoting sexual function.…”

Section: L-arginine: Rationale For Its Use In Vascular Diseasesmentioning

confidence: 99%

Herbal Viagra and nitric oxide: how hard is the evidence?

Cooke¹

2010

Cureus

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Asymmetric dimethyl arginine levels correlate with cardiovascular risk factors in patients with erectile dysfunction

Cited by 33 publications

References 32 publications

Dimethylarginine dimethylaminohydrolase in rat penile tissue: reduced enzyme activity is responsible for erectile dysfunction in a rat model of atherosclerosis

Dimethylarginine dimethylaminohydrolase in rat penile tissue: reduced enzyme activity is responsible for erectile dysfunction in a rat model of atherosclerosis

Statins and hypertension

Herbal Viagra and nitric oxide: how hard is the evidence?

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