Simvastatin increases plasma NO2− and NO3− levels in patients with hypercholesterolemia

Nakashima, Yasuhide; Toyokawa, Takahiro; Tanaka, Seiya; Yamashita, Kazuhito; Yashiro, Akira; Tasaki, Hiromi; Kuroiwa, Akio

doi:10.1016/s0021-9150(96)05933-3

Cited by 11 publications

(12 citation statements)

References 21 publications

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“…Besides the present study, we also previously demonstrated that long-term treatment with simvastatin, a HMG-CoA reductase inhibitor, significantly enhances plasma NOx concentration in patients with hypercholesterolemia (16) and that plasma NOx level is inversely correlated with plasma level of lowdensity lipoprotein cholesterol in humans (24). However, whether NOx is a reliable marker of NO formation in vivo is still controversial, and indeed there are conflicting facts regarding plasma NOx level in hypertensive individuals: two studies reported that plasma NOx concentrations were significantly reduced in patients with essential hypertension compared to those in normotensive healthy subjects (12,25) whereas one study showed that plasma NOx levels were similar in refractory hypertensive patients and normotensive healthy subjects (26).…”

Section: Nox As a Marker Of No Formation In Vivosupporting

confidence: 81%

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Long-Term Treatment With Imidapril but Not With Nifedipine Enhances Plasma NOx Concentration in Patients With Essential Hypertension

et al. 2006

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Abstract. We investigated whether long-term treatment with the angiotensin-converting enzyme (ACE) inhibitor imidapril or the calcium channel antagonist nifedipine increases systemic nitric oxide (NO) production in patients with essential hypertension. Twenty-nine patients with essential hypertension were randomly divided into two groups, and they were treated with either imidapril or nifedipine once daily p.o. for 4 weeks. Long-term treatment with imidapril significantly decreased blood pressure and increased plasma NOx concentration. Long-term treatment with nifedipine also caused a comparable extent of significant decrease in blood pressure, but failed to alter plasma NOx levels. The imidapril treatment significantly inhibited serum ACE activity and increased plasma bradykinin concentration. Furthermore, the extent of inhibition of serum ACE activity and the extent of increase in plasma bradykinin concentration in response to the imidapril treatment were both significantly correlated with the extent of increase in plasma NOx concentration. In contrast, no such changes were noted after the nifedipine treatment. These results provide the first evidence that long-term treatment with imidapril enhances plasma NOx concentration in patients with essential hypertension. This effect does not seem to be due to the decrease in blood pressure. The increase in bradykinin concentration may be involved in the enhancing effect of the ACE inhibitor on NOx production in vivo.

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Section: Nox As a Marker Of No Formation In Vivosupporting

confidence: 81%

“…The blood samples were immediately centrifuged at 3,000 rpm, 4°C for 15 min, and the supernatants were stored at −80°C. Plasma NOx concentration were assessed by the Griess method, as we previously reported (16,17). Serum ACE activity was measured by the Kasahara method (18).…”

Section: Measurementmentioning

confidence: 99%

Long-Term Treatment With Imidapril but Not With Nifedipine Enhances Plasma NOx Concentration in Patients With Essential Hypertension

et al. 2006

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“…They also found temporal variability in NOx levels, which were most reproducible and lowest at 0600 [64]. This confirmed the work of Nakashima, who found that treatment of hypercholesterolemic adults with the cholesterol lowering agent, Simvastatin, increases plasma NOx (from 8 ± 17 µmol/l to 57 ± 32 µmol/l), within 12 weeks, in a manner that correlated with the rise in high density lipoprotein [65]. …”

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Measurement of nitric oxide, nitrite and nitrate using a chemiluminescence assay:an update for the year 2000

McMurtry¹,

Kim²,

Dinh-Xuan³

et al. 2000

Analusis

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This review deals with the measurement of nitric oxide (NO) using the chemiluminescence assay. A preliminary discussion is offered to explain the chemical basis for this assay and emphasize the importance of measuring NO. After reviewing some practical aspects and caveats of the chemiluminescence assay, we review its application in a variety of research and clinical settings, such as measurement of breath NO and serum nitrates. The importance of avoiding confounding effects of dietary nitrates when assessing the NO system in humans is discussed and new data are provided on the confounding effects of atmospheric NO on measurement of breath NO. The utility and ease of the chemiluminescence assay for these applications is contrasted with the challenge of using chemiluminescence for correlation of vascular tone and NO production, studies in which real-time measurements are required. Although the chemiluminescence assay is one of the most reliable, rapid and reproducible assays available, it is optimal for gas phase measurements and may be suboptimal for measurement under certain circumstances. This chapter complements several more general reviews of the methodology for measuring NO.Article available at http://analusis.edpsciences.org or http://dx.doi.org/10.1051/analusis:2000280455 Need for measuring NOIt is clear that NO is essential in a significant number of normal physiological processes. However, the scope of its importance also spans pathophysiology of disease, such as in cardiogenic shock [14,15]. Inhaled NO is used for diagnostic purposes, and has therapeutic value, in diseases such as pulmonary hypertension [16][17][18], asthma and chronic obstructive lung diseases [12,[19][20][21]. NO may even promote regression of diseases, such as atherosclerosis [22,23].In view of the broad biological importance of this molecule, it is not surprising that basic and clinical research pertaining to NO has been so prolific. However, a computerised search of the past five years' literature found NO measurements reported in only 1089 of 26123 articles dealing with NO. Since many scientists don't measure NO, perhaps we should make the case for measurement explicit.There are four major reasons why one should consider measuring NO: Non specificity of NO inhibitorsPharmacological experiments are useful in studying NO and its effects. Nevertheless, the non-specificity of NO inhibitors [24][25][26] impairs one's ability to draw sound mechanistic conclusions. For instance, N G -monomethyl-L-arginine (L-NMMA), a NOS antagonist, displays hemodynamic effects that are not solely mediated by its ability to inhibit NO synthesis [27]. L-NMMA can also be metabolized to yield NO. Furthermore, even high doses of NOS inhibitors do not completely prevent NO synthesis [28]. Without measuring NO one cannot be assured that the observed effects resulting from administration of a NOS inhibitor reflect the complete loss of NO, nor can one exclude non-specific effects of these inhibitors. The existence of multiple endothelium-derived vasodilatorsIt i...

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“…29 NO release in the coronary arteries was directly measured with an NO-sensitive electrode (Model 501; Inter Medical Co, Nagoya, Japan). 14,30 The mouse hearts were isolated and a NO-sensitive electrode was stuck and placed perpendicularly into the left anterior descending coronary artery in oxygenated Krebs-Ringer bicarbonate solution at 37°C.…”

Section: Measurement Of Nitrite Plus Nitrate and Nomentioning

confidence: 99%

Asymmetric Dimethylarginine Produces Vascular Lesions in Endothelial Nitric Oxide Synthase–Deficient Mice

Suda

Tsutsui

Morishita

et al. 2004

ATVB

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124

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Objective-Asymmetric dimethylarginine (ADMA) is widely believed to be an endogenous nitric oxide synthase (eNOS) inhibitor. However, in this study, we examined our hypothesis that the long-term vascular effects of ADMA are not mediated by inhibition of endothelial NO synthesis. Methods and Results-ADMA was infused in wild-type and eNOS-knockout (KO) mice by osmotic minipump for 4 weeks. In wild-type mice, long-term treatment with ADMA caused significant coronary microvascular lesions. Importantly, in eNOS-KO mice, treatment with ADMA also caused an extent of coronary microvascular lesions that was comparable to that in wild-type mice. These vascular effects of ADMA were not prevented by supplementation of L-arginine, and vascular NO production was not reduced by ADMA treatment. Treatment with ADMA caused upregulation of angiotensin-converting enzyme (ACE) and an increase in superoxide production that were comparable in both strains and that were abolished by simultaneous treatment with temocapril (ACE inhibitor) or olmesartan (AT 1 receptor antagonist), which simultaneously suppressed vascular lesion formation. Key Words: asymmetric dimethylarginine Ⅲ arteriosclerosis Ⅲ nitric oxide Ⅲ endothelial nitric oxide synthase Ⅲ mice E ndothelium-derived nitric oxide (NO), synthesized from L-arginine by endothelial NO synthase (eNOS), has several important antiatherogenic actions. 1-5 Indeed, reduction of endothelial NO synthesis (endothelial dysfunction) predisposes the blood vessel to arteriosclerosis, 1-5 and the eNOS-deficient (eNOS-KO) mice exhibit accelerated vascular lesion formation. 6,7 As pharmacological tools to inhibit endothelial NO synthesis, synthetic L-arginine analogues have been used in vitro and in vivo. Among them, N -nitro-L-arginine methyl ester (L-NAME) is the most frequently used agent. [1][2][3][4][5] Long-term treatment with L-NAME is known to cause arteriosclerotic coronary lesions, especially at microvascular levels, in experimental animals. 8,9 This model with L-NAME is regarded as a useful animal model for examining the protective roles of endothelium-derived NO in the pathogenesis of arteriosclerosis. 8,9 See cover However, it is controversial whether these vascular effects of L-NAME are caused primarily by the inhibition of endothelial NO synthesis for the following reasons: first, the importance of endothelium-derived NO decreases as the vessel size becomes smaller, 10 whereas L-NAME-induced vascular lesions are prominent at microvascular levels; 8 second, long-term treatment with L-NAME does not reduce eNOS activity; 11 third, multiple actions of L-NAME other than simple inhibition of NO synthesis have been reported. 12,13 The most appropriate way to address this issue is to use mice that are deficient in the eNOS gene and to examine whether long-term treatment with L-NAME causes coronary vascular lesions in those mice. We have recently shown that treatment with L-NAME causes a comparable extent of Conclusions-These

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Simvastatin increases plasma NO2− and NO3− levels in patients with hypercholesterolemia

Cited by 11 publications

References 21 publications

Long-Term Treatment With Imidapril but Not With Nifedipine Enhances Plasma NOx Concentration in Patients With Essential Hypertension

Long-Term Treatment With Imidapril but Not With Nifedipine Enhances Plasma NOx Concentration in Patients With Essential Hypertension

Measurement of nitric oxide, nitrite and nitrate using a chemiluminescence assay:an update for the year 2000

Asymmetric Dimethylarginine Produces Vascular Lesions in Endothelial Nitric Oxide Synthase–Deficient Mice

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