Direct inhibition of platelet function by organic nitrates via nitric oxide formation

Weber, Artur‐Aron; Strobach, H.; Schrör, Karsten

doi:10.1016/0922-4106(93)90134-u

Cited by 58 publications

(26 citation statements)

References 26 publications

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“…The cGMP levels of washed platelets was determined in supernatants after neutralization with bicarbonate (24) using a radioimmunassay (cGMP [ 125 I] RIA Kit; BioTrend, Cologne, Germany; reference 23). To determine cGMP content in phosphodiesterase-inhibited platelets, cells were incubated with 20 M zaprinast for 10 min (25).…”

Section: Methodsmentioning

confidence: 99%

Dietary supplement with vitamin C prevents nitrate tolerance.

Bassenge¹,

Fink²,

Skatchkov³

et al. 1998

J. Clin. Invest.

129

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Enhanced formation of superoxide radicals has been proposed to play a major role in the development of nitrate tolerance in humans. We tested the effects of vitamin C (Vit-C) supplementation on glyceroltrinitrate (GTN)-induced hemodynamic effects during 3-d nonintermittent transdermal administration of GTN (0.4 mg/h) in nine healthy subjects. Tolerance development was monitored by changes in arterial pressure, dicrotic digital pulse pressure, and heart rate. Studies with GTN, Vit-C, or GTN/Vit-C were successively carried out at random in three different series in the same subjects. GTN treatment caused an immediate rise in arterial conductivity (a/b ratio of dicrotic pulse), but within 2 d of initiating GTN, the a/b ratio progressively decreased and reached basal levels. In addition, there was a progressive loss of the orthostatic decrease in blood pressure. However, coadministration of Vit-C and GTN fully maintained the GTN-induced changes in the orthostatic blood pressure, and the rise of a/b ratio was augmented by 310% for the duration of the test period. Changes in vascular tolerance in GTN-treated subjects were paralleled by upregulation of the activity of isolated platelets, which was also reversed by

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Section: Methodsmentioning

confidence: 99%

Dietary supplement with vitamin C prevents nitrate tolerance.

Bassenge¹,

Fink²,

Skatchkov³

et al. 1998

J. Clin. Invest.

129

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show abstract

“…increasing the blood flow to the developing placenta. NO also inhibits the aggregation and adhesion of platelets (Weber et al, 1993). The local production of NO may be critical to the prevention of thrombus formation within the placenta.…”

Section: Discussionmentioning

confidence: 99%

Localization of NADPH diaphorase in the mouse uterus during the first half of pregnancy and during an artificially induced decidual cell reaction.

Moorhead

Lawhun²,

Nieder³

1995

J Histochem Cytochem.

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Uteri from non-pregnant and pregnant (Days 1-10) mice were examined for the presence of NADPH diaphorase (NADPH-d) activity by histochemical techniques. Macrophages positive for NADPH-d were observed in all uterine sections but appeared to migrate out of the implantation site and cluster in the mesometrium and interimplantation zones beginning on Day 4. NADPH-d activity was seen in the luminal and glandular epithelium and in several isolated fibers coursing through the myometrium. Many branches of the uterine artery also expressed activity, with the most intense staining in the vessels of the mesometrium. However, the most remarkable staining began on Day 6 within the primary decidual zone. When the stromal cells underwent decidualization, they began to show NADPH-d activity, with the pattern of activity matching the expanding area

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“…eNOS inhibition increases platelet aggregability, whereas NO donors such as nitrates are potent anti-aggregant drugs [35,36,37]. Therefore, we measured the in vitro bleeding time to assess the platelet L -arginine/NO pathway and hence to test whether or not statins upregulate the activity of this pathway in humans at clinically relevant doses.…”

Section: Discussionmentioning

confidence: 99%

Statin Potentiates Human Platelet eNOS Activity without Enhancing eNOS mRNA and Protein Levels

Yemişçi

Kocaefe³

et al. 2008

Cerebrovasc Dis

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Background/Aims: Experimental studies suggest an enhanced endothelial and platelet nitric oxide (NO) generation after statin treatment, possibly due to increased endothelial NO synthase (eNOS) activity and protein levels. In parallel with experimental research, statins were shown to increase the forearm blood flow independently of serum cholesterol in humans. However, it was not possible to correlate blood flow changes with eNOS levels in these studies due to limitations in obtaining arterial samples. Hence, we investigated changes in eNOS activity, mRNA and protein levels after statin treatment in human platelets, which are readily accessible unlike arteries. Methods: In vitro bleeding times were measured in 22 patients by stimulating platelets with collagen-epinephrine or collagen-ADP. To assess platelet eNOS activity, the bleeding times were also determined after incubating platelets with L-arginine. The measurements were repeated following 14 days of pravastatin (40 mg/day) treatment. Platelet-rich plasma was collected before and after statin treatment to evaluate eNOS mRNA (semiquantitative RT-PCR) and protein levels (Western blotting). Results: The basal bleeding time was prolonged by 24 ± 3% (mean ± SE) when the samples were incubated with 500 µM of L-arginine. The NOS inhibitor L-N⁵-(I-iminoethyl)ornithine reversed this effect, suggesting that it was mediated by NO. After statin treatment, the NO-mediated prolongation of the bleeding time with 500 µM of L-arginine was significantly potentiated (to 44 ± 10%). Despite enhanced eNOS activity, there was no significant change in platelet eNOS mRNA and protein levels after statin treatment. Conclusion: These data demonstrate that platelet eNOS activity is potentiated after statin treatment in humans in parallel with experimental studies.

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Direct inhibition of platelet function by organic nitrates via nitric oxide formation

Cited by 58 publications

References 26 publications

Dietary supplement with vitamin C prevents nitrate tolerance.

Dietary supplement with vitamin C prevents nitrate tolerance.

Localization of NADPH diaphorase in the mouse uterus during the first half of pregnancy and during an artificially induced decidual cell reaction.

Statin Potentiates Human Platelet eNOS Activity without Enhancing eNOS mRNA and Protein Levels

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