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Nitrate Tolerance (nitrate + tolerance)
Selected AbstractsTwo Possible Mechanisms Underlying Nitrate Tolerance In Monkey Coronary ArteriesCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 4 2001Tomoko Omura SUMMARY 1. Previous studies using isolated arteries have demonstrated cross-tolerance between nitric oxide (NO) donors such as nitroglycerin (NTG) and sodium nitroprusside (SNP). However, it remains unclear whether the vasorelaxing effect of atrial natriuretic peptide (ANP), an activator of particulate guanylate cyclase, is affected by treatment with NO donors. To investigate the cross-tolerance and interactions between NTG and ANP in coronary vasorelaxant responses, we used two models of monkey coronary arterial strips (Macaca fuscata). 2. In one model, which was induced by a 1 h treatment with 4.4 × 10,4 mol/L NTG followed by washout of the agent for 1 h, the vasorelaxing effects of subsequent NTG were markedly attenuated, whereas those of ANP and NO were not affected. These findings suggest that the development of NTG tolerance is associated with a biotransformation process from NTG to NO. In the other model, which did not include washout after exposure to 3 × 10,6 mol/L NTG, the vasorelaxant responses to 10,8 mol/L ANP (31.1±5.4 vs 5.1±2.1%, respectively; P < 0.001), 10,6 mol/L NO (61.5±2.4 vs 29.5±8.5%, respectively; P < 0.001) and 10,8 mol/L SNP (49.4±6.4 vs 8.0±2.0%, respectively; P < 0.001) were significantly attenuated. The concentration, response curve for 8-bromo-cGMP (8-Br-cGMP) was shifted to the right, whereas responses to papaverine and forskolin were unchanged. These findings suggest that an intracellular process that occurs after the synthesis of cGMP is responsible for this interaction. 3. As a mechanism of NTG tolerance, two possible processes may be impaired: (i) biotransformation from NTG to NO; and (ii) an intracellular process that occurs after the synthesis of cGMP. [source] Mechanisms of nitrate tolerance: potential roles of folateEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 11 2003F. Iachini Bellisarii Abstract More than 100 years since their introduction in cardiovascular therapy, nitrates continue to be widely used in ischaemic heart disease despite incomplete knowledge of their intimate mechanism of action. Particularly, the development of a progressive attenuation of their efficacy over prolonged use (tolerance) continues to be the subject of current investigation. Newer findings point to the role of increased intracellular oxidative stress as a mechanism for tolerance and to folic acid derivatives as pharmacologic means to attenuate its development. This paper reviews nitrate mechanism of action, the history of nitrate tolerance and newer findings related to the use of folate to prevent this phenomenon. [source] Impact of nitrate supply in C and N assimilation in the parasitic plant Striga hermonthica (Del.) Benth (Scrophulariaceae) and its host Sorghum bicolor L.PLANT CELL & ENVIRONMENT, Issue 4 2006P. SIMIER ABSTRACT The threshold of tolerance for nitrate of the parasitic weed Striga hermonthica (Del.) Benth and the host plant Sorghum bicolor L. was determined by estimating the impact of increasing nitrate loads on plant growth and various parameters of C and N assimilation. Nitrate supply improved chlorophyll (Chl) content and photosystem II (PSII) photochemistry of infected S. bicolor that, in comparison to S. hermonthica, displayed a low imbalance between C and N assimilation when nitrate was supplied up to 1500 mg N per plant. Indeed, nitrate supplies increased strongly the leaf N:C ratio of the parasite. The higher nitrate load induced strong accumulation of nitrate, nitrite and ammonium, and consequently the death of S. hermonthica. Nevertheless, lower nitrate loads (up to 500 mg N per S. bicolor in this study) promoted leaf expansion, PSII photochemistry and N metabolism of S. hermonthica mature (M) plants, as attested by the significant rise in soluble protein and free amino-acid contents. Following these N supplies, the nitrate tolerance of S. hermonthica was correlated with an increase in PSII activity and a high incorporation of N excess into asparagine. This confirmed the central role of asparagine in the N metabolism of S. hermonthica, although this detoxification pathway was insufficient to limit ammonium accumulation under higher nitrate loads. [source] Lack of critical involvement of endothelial nitric oxide synthase in vascular nitrate tolerance in miceBRITISH JOURNAL OF PHARMACOLOGY, Issue 2 2002Ellen Q Wang We examined the direct involvement of endothelial nitric oxide (eNOS) in nitrate tolerance using eNOS knockout (eNOS (,/,)) and wild-type (eNOS (+/+)) mice. Animals were treated with either nitroglycerin (NTG, 20 mg kg,1s.c. 3×daily for 3 days) or vehicle (5% dextrose, D5W), and nitrate tolerance was assessed ex vivo in isolated aorta by vascular relaxation studies and cyclic GMP accumulation. Western blot was performed to determine NOS expression after NTG treatment. In both the eNOS (,/,) and (+/+) mice, the EC50 from NTG concentration-response curve was increased by ,3 fold, and vascular cyclic GMP accumulation was similarly decreased after NTG pretreatment. Vascular tolerance did not lead to changes in eNOS protein expression in eNOS (+/+) mice. These results indicate that vascular nitrate tolerance was similarly induced in eNOS (,/,) and (+/+) mice, suggesting that eNOS may not be critically involved in nitrate tolerance development in mice. British Journal of Pharmacology (2002) 135, 299,302; doi:10.1038/sj.bjp.0704532 [source] A Short History Of Nitroglycerine And Nitric Oxide In Pharmacology And PhysiologyCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 4 2000Neville Marsh SUMMARY 1. Nitroglycerine (NG) was discovered in 1847 by Ascanio Sobrero in Turin, following work with Theophile-Jules Pelouze. Sobrero first noted the ,violent headache' produced by minute quantities of NG on the tongue. 2. Constantin Hering, in 1849, tested NG in healthy volunteers, observing that headache was caused with ,such precision'. Hering pursued NG (,glonoine') as a homeopathic remedy for headache, believing that its use fell within the doctrine of ,like cures like'. 3. Alfred Nobel joined Pelouze in 1851 and recognized the potential of NG. He began manufacturing NG in Sweden, overcoming handling problems with his patent detonator. Nobel suffered acutely from angina and was later to refuse NG as a treatment. 4. During the mid-19th century, scientists in Britain took an interest in the newly discovered amyl nitrite, recognized as a powerful vasodilator. Lauder Brunton, the father of modern pharmacology, used the compound to relieve angina in 1867, noting the pharmacological resistance to repeated doses. 5. William Murrell first used NG for angina in 1876, although NG entered the British Pharmacopoeia as a remedy for hypertension. William Martindale, the pharmaceutical chemist, prepared ,. . . a more stable and portable preparation': 1/100th of a grain in chocolate. 6. In the early 20th century, scientists worked on in vitro actions of nitrate-containing compounds although little progress was made towards understanding the cellular mode of action. 7. The NG industry flourished from 1900, exposing workers to high levels of organic nitrites; the phenomena of nitrate tolerance was recognized by the onset of ,Monday disease' and of nitrate-withdrawal/overcompensation by ,Sunday Heart Attacks'. 8. Ferid Murad discovered the release of nitric oxide (NO) from NG and its action on vascular smooth muscle (in 1977). Robert Furchgott and John Zawadski recognized the importance of the endothelium in acetylcholine-induced vasorelaxation (in 1980) and Louis Ignarro and Salvador Moncada identified endothelial-derived relaxing factor (EDRF) as NO (in 1987). 9. Glycerol trinitrate remains the treatment of choice for relieving angina; other organic esters and inorganic nitrates are also used, but the rapid action of NG and its established efficacy make it the mainstay of angina pectoris relief. [source] | ||||||||||