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Desensitization of nitrate-induced venodilation: reversal with oral N-acetylcysteine in humans
- Source :
- Journal of cardiovascular pharmacology. 20(6)
- Publication Year :
- 1992
-
Abstract
- The objective of this study was to determine whether the dorsal hand vein could be used as a model to study tolerance to oral nitrates, and whether oral N-acetylcysteine (NAC) could reverse tolerance if present. Dose-response curves to nitroglycerin were constructed for 11 normotensive volunteers before and during treatment with a sustained-release formulation of isosorbide dinitrate, 80 mg, three times daily for 7 days and followed by concurrent treatment with NAC at a mean dose of 150 mg/kg/day, in divided doses, for 2 days. In separate studies, dose-response curves were constructed for seven normotensive volunteers before and after treatment with oral NAC at the same dose for 2 days. Nitroglycerin's Emax was significantly attenuated from 115 +/- 36 to 77 +/- 22% after treatment with isosorbide dinitrate alone (p < 0.009). Concurrent treatment with NAC reversed this decrease, as nitroglycerin's Emax of 108 +/- 26% during coadministration of isosorbide dinitrate and NAC was not different from its Emax in the control period. There was also no difference in the dose of phenylephrine required to cause 80% of maximal venoconstriction throughout the study. These studies demonstrate that smooth muscle tolerance to nitrates can be demonstrated in medium-sized veins in humans. In addition, high-dose oral NAC can reverse existing tolerance to oral nitrates in human veins. These results indicate that the dorsal hand vein compliance technique is a good model for the clinical investigation of tolerance to nitrates in humans.
- Subjects :
- Adult
Male
Isosorbide
Hemodynamics
Vasodilation
Isosorbide Dinitrate
Nitroglycerin
medicine
Humans
Phenylephrine
Pharmacology
Dose-Response Relationship, Drug
business.industry
Blood Pressure Determination
Drug Tolerance
Hand
Acetylcysteine
medicine.anatomical_structure
Regional Blood Flow
Anesthesia
Circulatory system
Female
Isosorbide dinitrate
Cardiology and Cardiovascular Medicine
business
Reverse tolerance
medicine.drug
Blood vessel
Subjects
Details
- ISSN :
- 01602446
- Volume :
- 20
- Issue :
- 6
- Database :
- OpenAIRE
- Journal :
- Journal of cardiovascular pharmacology
- Accession number :
- edsair.doi.dedup.....ed61571970e3a15ee1bd1298109a9d05