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NG-methyl-L-arginine causes endothelium-dependent contraction and inhibition of cyclic GMP formation in artery and vein.
- Source :
-
Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 1990 Jun; Vol. 87 (12), pp. 4430-4. - Publication Year :
- 1990
-
Abstract
- The objective of this study was to determine whether the vascular smooth muscle contractile effect of NG-methyl-L-arginine (NMA) is endothelium dependent and attributed to a decline in smooth muscle levels of cyclic GMP. Vascular smooth muscle levels of cyclic GMP are severalfold greater in endothelium-intact than in endothelium-denuded preparations because of the continuous formation and release of a lipophilic endothelium-derived chemical factor that diffuses into the underlying smooth muscle and activates cytosolic guanylate cyclase. This chemical substance, believed to be nitric oxide (NO) or a labile nitroso precursor, appears to account for the biological actions of endothelium-derived relaxing factor. NMA inhibits the formation of NO from endogenous L-arginine in endothelial cells. In the present study, NMA caused marked endothelium-dependent contraction of isolated rings of bovine pulmonary artery and vein, and this was similar to the contraction elicited by hemoglobin, an inhibitor of the relaxant action of NO. Both NMA and hemoglobin caused endothelium-dependent potentiation of contractile responses to phenylephrine in artery and vein. NMA caused endothelium-dependent decreases in the resting or basal levels of cyclic GMP in artery and vein to levels that were characteristic of those in endothelium-denuded vessels. Finally, NMA inhibited endothelium-dependent relaxant responses and cyclic GMP formation stimulated by acetylcholine and bradykinin. These observations reveal that interference with the continuous or basal generation of endothelium-derived NO in artery and vein can cause marked increases in vascular smooth muscle tone as a result of inhibition of cyclic GMP formation.
- Subjects :
- Acetylcholine pharmacology
Animals
Arginine pharmacology
Bradykinin pharmacology
Cattle
In Vitro Techniques
Kinetics
Muscle, Smooth, Vascular drug effects
Oxyhemoglobins pharmacology
Phenylephrine pharmacology
Pulmonary Artery drug effects
Pulmonary Veins drug effects
omega-N-Methylarginine
Arginine analogs & derivatives
Cyclic GMP metabolism
Endothelium, Vascular physiology
Muscle, Smooth, Vascular physiology
Pulmonary Artery physiology
Pulmonary Veins physiology
Vasoconstriction drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 0027-8424
- Volume :
- 87
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type :
- Academic Journal
- Accession number :
- 2162040
- Full Text :
- https://doi.org/10.1073/pnas.87.12.4430