We hypothesize that nitroglycerin (NTG) causes direct oxidation of multiple cellular sulfhydryl (SH) proteins and that manipulation of SH redox status affects NTG tolerance. In LLC-PK1 cells, we found that nitrate tolerance, as indicated by cGMP accumulation toward NTG, was accompanied by increased protein [(35)S]cysteine incorporation, significant S-glutathionylation of multiple proteins, and ...

OBJECTIVES We investigated the development of nitrate tolerance after continuous exposure to nitroglycerin (GTN) as compared with pentaerythritol tetranitrate (PETN) in humans. BACKGROUND Sustained therapy with GTN causes tolerance and has been associated with increased production of free oxygen radicals by the endothelium. Pentaerythritol tetranitrate is an organic nitrate that has been used...

a pot experiment was designed to evaluate the effect of trichoderma spp. on yield and yield components of wheat (cv. n81) under different levels of cadmium nitrate. experiment was arranged in factorial based on completely randomized design with three replicates. trichoderma harzianum at two levels (with and without inoculation) and four levels of cadmium nitrate (0, 50, 100, 150 mg l-1) were th...

Our purpose was to evaluate hyporesponsivity to nitric oxide (NO)-induced dilation in small arterioles during nitrate tolerance. An Alza osmotic pump was implanted in the left flank of adult rats (n = 56) for continuous administration of nitroglycerin (140 microg/h) or vehicle (propylene glycol). On postoperative day 3, arcade (approximately 50-microm diameter) and terminal (approximately 20 mi...

Previously, it was shown that the D enantiomer of isoidide dinitrate was 10-fold more potent than the L enantiomer and 10-fold less potent than glyceryl trinitrate for stimulating cyclic GMP accumulation and relaxation of isolated rat aorta. In the present study, these organic nitrates were tested for their ability to induce tolerance to organic nitrate-induced relaxation, cyclic GMP accumulati...

Nitroglycerin (glyceryl trinitrate, GTN), originally manufactured by Alfred Nobel, has been used to treat angina and heart failure for over 130 years. However, the molecular mechanism of GTN biotransformation has remained a mystery and it is not well understood why "tolerance" (i.e., loss of clinical efficacy) manifests over time. Here we purify a nitrate reductase that specifically catalyzes t...

AIMS Reduced bioavailability of endogenous nitric oxide (NO) is a central pathophysiological event in hypertension and other cardiovascular diseases. Recently, it was demonstrated that inorganic nitrate from dietary sources is converted in vivo to form nitrite, NO, and other bioactive nitrogen oxides. We tested the hypothesis that dietary inorganic nitrate supplementation may have therapeutic e...

BACKGROUND We have previously shown that nitroglycerin (NTG) therapy increases vascular expression of endothelin 1 (ET-1) and stimulates vascular superoxide (O2.-) production via activation of NADH/NADPH oxidases. Both phenomena are stimulated by angiotensin II in vitro, and the renin-angiotensin system is activated during early nitrate therapy. We hypothesized that either angiotensin II or ET-...