link1: Cell Biochem Funct. 2007 Sep-Oct;25(5):485-90. Links
Effects of vitamin K1 supplementation on vascular responsiveness and oxidative stress in a rat femoral osteotomy model.Tasatargil A, Cadir B, Dalaklioglu S, Yurdakonar E, Caglar S, Turkay C.
Department of Pharmacology, Medical Faculty, Akdeniz University, Antalya, Turkey. email@example.com
The main function of vitamin K1 is to act a co-factor for gamma-glutamyl carboxylase. However, it has also been shown to lessen oxidative stress. This study was aimed to evaluate the effect of vitamin K1 supplementation on vascular responsiveness and oxidative status in rats that underwent femoral osteotomy. Twenty-four male rats were divided into three groups to serve as sham, osteotomy and vitamin K1 groups. Indices of oxidative stress (catalase), and oxidative damage (malondialdehyde) were analysed in erythrocytes. In order to evaluate vascular reactivity, concentration-response curves to phenylephrine, angiotensin II, 5-hydroxytryptamine, bradykinin and histamine were constructed. The findings of this study clearly show that oxidative stress clearly increases after femoral osteotomy in rats. Also, this operation causes a significant depression in vascular responsiveness to contracting agents and endothelium-dependent vasodilators. However, vitamin K1 supplementation prevents vascular hyporeactivity by reducing oxidative stress and may represent a novel approach during osteotomy healing.
PMID: 16929463 [PubMed - indexed for MEDLINE
link1: Toxicol Appl Pharmacol. 2006 May 15;213(1):10-7. Epub 2005 Oct 26. Links
Vitamin K1 (phylloquinone) induces vascular endothelial dysfunction: role of oxidative stress.Tirapelli CR, De Andrade CR, Lieberman M, Laurindo FR, De Souza HP, de Oliveira AM.
Department of Pharmacology, Faculty of Medicine of Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil.
We aimed to investigate the mechanisms underlying the vascular effects induced by phylloquinone (Vitamin K1; VK1). Vascular reactivity experiments, using standard muscle bath procedures, showed that VK1 (5 and 50 microM) enhances the contractile response of endothelium-intact, but not denuded, rat carotid rings to phenylephrine. Similarly, maximal contraction induced by phenylephrine was enhanced in the presence of the nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME). The combination of L-NAME and VK1 did not produce any further additional effect. Pre-incubation of intact-rings with VK1 reduced both acetylcholine- and bradykinin-induced relaxation. VK1 induced an increment in tension on carotid rings submaximally pre-contracted with phenylephrine. VK1-induced increment in tension was completely abolished by endothelial removal or incubation of intact rings with L-NAME and L-NNA. Conversely, 7-nitroindazole, 1400 W, or indomethacin did not affect VK1-induced contraction. Moreover, VK1 reduced L-arginine-induced relaxation in endothelium-intact rings. Lucigenin-amplified chemiluminescence assays showed that VK1 induced an increase in the level of superoxide anions in endothelium-intact but not denuded rings. Measurement of nitrite and nitrate generation showed that VK1 did not alter nitrate formation but strongly inhibited the generation of nitrite. Finally, the superoxide anions scavenger tiron prevented the endothelial vasomotor dysfunction caused by VK1 on phenyleprine-induced contraction and acetylcholine or bradykinin-induced relaxation. In conclusion, our data show that VK1 disrupts the vasomotor function of rat carotid. Our results suggest that VK1-induced oxidative stress through production of superoxide anion is interfering with the NO pathway, which in turn is responsible for the altered vascular reactivity induced by VK1.
PMID: 16256160 [PubMed - indexed for MEDLINE
link1: J Nutr Sci Vitaminol (Tokyo). 1999 Dec;45(6):711-23.Links
Vitamin K2 (menatetrenone) induces iNOS in bovine vascular smooth muscle cells: no relationship between nitric oxide production and gamma-carboxylation.Sano M, Fujita H, Morita I, Uematsu H, Murota S.
Department of Physiological Chemistry, Graduate School, Tokyo Medical and Dental University, Japan.
It has been recently reported that vitamin K2 (menaquinone-4: menatetrenone, VK2) has an anti-atherogenic effect as well as the ability to produce clotting factors and improve osteoporosis. However, the mechanism by which VK2 acts on atherosclerosis is still unclear. In this paper, we investigated the effects of vitamin K and its side chain on NO production as an anti-atherogenic substance in a cultured vascular system. Treatment of bovine vascular smooth muscle cells (SMC) with VK2 (30 microM) caused a time-dependent (24-72 h) increase in the nitrite (NO2) level in the conditioned medium, but not in bovine vascular endothelial cells. Classical NOS inhibitor (L-nitro arginine) and iNOS-specific inhibitors completely blocked the increased nitrite level induced by VK2 treatment, but D-nitro arginine could not it. Immunostaining and Western blotting analysis showed that VK2 induced iNOS protein in the SMC. VK2 has a naphtoquinone nucleus, which is identical in menadione (VK3), and an unsaturated side chain, which is called geranylgeraniol (GGO). To determine whether the structure of VK2 was related to an increasing nitrite level, we investigated the nitrite level in conditioned medium treated with VK3 or GGO. Neither VK3 nor GGO treatment of SMC increased the nitrite level. In addition, warfarin, an inhibitor of VK2-dependent gamma-carboxylation, did not affect the increased nitrite level induced by VK2 in SMC. In conclusion, VK2 caused NO production through iNOS induction in bovine SMC, that was not related to the structure of VK2, naphtoquinone nucleus or its side chain, independently of gamma-carboxylation.
PMID: 10737225 [PubMed - indexed for MEDLINE]
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Warfarin (Coumadin®) Warfarin is used to prevent blood clots from forming or growing larger in your blood and blood vessels. It is prescribed for people with certain types of irregular heartbeat, people with prosthetic (replacement or mechan... » read more ...
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