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Studies of vascular tolerance to nitroglycerin: effects of N-acetylcysteine, NG-monomethyl L-arginine, and endothelin-1


, : Studies of vascular tolerance to nitroglycerin: effects of N-acetylcysteine, NG-monomethyl L-arginine, and endothelin-1. Journal of Cardiovascular Pharmacology 28(3): 418-424

Development of vascular tolerance to nitroglycerin (NTG) has been attributed to sulfhydryl (SH) depletion, guanylate cyclase desensitization, or both. Controversy regarding the precise contribution of these mechanisms may be due to variations in experimental design. To examine further the biochemical basis of NTG tolerance, norepinephrine (NE)-precontracted rat aortic rings were exposed to NTG (10(-5)M), which resulted in 84 +/- 6% relaxation. Other rings were first superfused with NTG (10(-6)M) and then contracted with NE. These rings showed a marked tolerance to the vasorelaxant effects of NTG (maximal relaxation 20 +/- 5%, n = 15, p < 0.001 vs. control rings). Similar tolerance to NTG was observed when the vascular rings were first superfused with acetylcholine (ACh 10(-6)M), indicating cross-tolerance between ACh and NTG. Treatment of NTG-tolerant rings with N-acetylcysteine (NAC) (10(-5)M) did not restore vascular smooth muscle (VSM) relaxation in response to NTG (maximal relaxation 23 +/- 5%, n = 8), suggesting that SH depletion may not be the basis of NTG tolerance in these experiments. Parallel sets of NTG-tolerant aortic rings were contracted with endothelin-1 (ET-1, n = 5) or the endothelium-derived relaxing factor (EDRF) synthase inhibitor NG-monomethyl L-arginine (L-NMMA, 10(-4)M, n = 8). In both ET-1- and L-NMMA-contracted rings, vascular relaxation in response to NTG was preserved (80 +/- 6 and 88 +/- 8% relaxation, respectively). Measurement of cyclic GMP in aortic rings showed marked accumulation on initial exposure of tissues to NTG (310 +/- 10 fmol/mg), whereas the NTG-tolerant rings showed much less cyclic GMP accumulation (48 +/- 29 fmol/mg). Rings contracted with L-NMMA or ET-1, but not NE, accumulated cyclic GMP when exposed to NTG (280 +/- 20 fmol/mg). These data indicate that NTG tolerance develops on exposure of vascular rings superfused with NTG or ACh and is probably not related to tissue SH depletion. Contraction of NTG-tolerant rings with ET-1 or L-NMMA restores NTG-mediated relaxation.

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PMID: 8877589


Other references

Mahaffey, Samuel M., 1997: Meconium syndromes and cystic fibrosis. Oldham, K T [Editor], Colombani, P M [Editor], Foglia, R P [Editor] Surgery of infants and children: Scientific principles and practice : 1183-1191

Yao J.K.; Yasaei P.; Van Kammen D.P., 1992: Increased turnover of platelet phosphatidylinositol in schizophrenia. The potential role of receptor-stimulated phosphatidylinositol (PI) hydrolysis in a signal transduction mechanism has been increasingly recognized. Earlier studies have suggested a defect in .alpha.-adrenergic receptor function in the platelets of...

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Schlegel, C.R.; Quintanilla, N.M.; Olive, A.P.; Minard, C.G.; Davis, C.M., 2014: Relationship of pediatric eosinophilic esophagitis diagnosis to pollen and mold counts. Annals of Allergy, Asthma & Immunology 113(3): 321-322

Tripathi, A.; Pandey, S.; Singh, S.V.; Kumar Sharma, N.; Singh, R., 2012: Bisphosphonate therapy for skeletal malignancies and metastases: impact on jaw bones and prosthodontic concerns. Healthy jawbones ensure better tooth anchorage and the ability to masticate and maintain metabolism. This is achieved by a delicate balance between bone formation and resorption in response to functional demands. An imbalance in the expression of...

Hase, Y.; Machida, Y.; Maotani, T., 1988: Influence of subsoil moisture on the growth of Japanese persimmon and its fruit yield. A study of soil moisture tensiometer readings (pF values) showed that tree growth and fruit yield of Diospyros kaki were poor when the pF was < 1.3 for 80% of the growing season. Growth and fruit yield were best when the pF was < 1.3 for les...

Andreenko, S.S.; Alekhina, N.D., 1966: Assimilation and conversion of nitrates by corn plants at various pH values of the nutrient solution. An increase of the acidity of the nutrient medium from pH 4.4-4.6 to 6.6-7.0 leads to appreciable changes in the absorption and conversion of nitrates by 15-day-old corn sprouts. The activity of nitrate reductase drops under the effect of high aci...

Kampf, D.; Kahl, A.; Passlick, J.; Pustelnik, A.; Eckardt, K.U.; Ehmer, B.; Jacobs, C.; Baumelou, A.; Grabensee, B.; Gahl, G.M., 1989: Single-dose kinetics of recombinant human erythropoietin after intravenous, subcutaneous and intraperitoneal administration. Preliminary results. Contributions to Nephrology 76: 106-10; Discussion 110-1

Bourouis, M., 2002: Targeted increase in shaggy activity levels blocks wingless signaling. We report two cases of bacteremia with Ochrobactrum anthropi in patients on hemodialysis. Bacteremia became clinically manifest by recurrent febrile episodes during and after dialysis. In one patient, bacteremia persisted after ciprofloxacin thera...