L-arginine-induced changes in the characteristics of endothelial relaxation.
The importance of the functional integrity of endothelium in maintaining vessel tone and the reversibility of its dysfunction by L-arginine (Arg) treatment has made this amino acid very unique and a topic of many experiments. As the behavior of normal vessels against L-Arg was not known properly, we studied the effect of 10(-2) M L-Arg on the dilating effect of Ach and on its characteristics in 10(-6) M phenylephrine-contracted rings prepared from normal rat thoracic aortae, where nitric oxide (NO) mediates most acetylcholine (Ach)-induced relaxation. L-arginine attenuated PE-induced contraction, and the pD2 value for phenylephrine shifted to the right from -log M 7.10 +/- 0.1 to -6.67 +/- 0.16. L-arginine supplementation also caused a tremendous change in the characteristics of Ach-induced dilation. The share of the indomethacin-sensitive part in the 10(-5) M Ach-induced dilation of L-Arg pretreated rings increased from 26.0 +/- 0.1 to 42.0 +/- 4.6%, whereas the L-NAME-sensitive component decreased from 74.0 +/- 1.6 to 29.0 +/- 3.8% (p<0.001). L-arginine led to the occurrence of a non-NO, non-PGI2 component (29.0 +/- 1.1%) in Ach dilation. When regarding the NO-based relaxing response of thoracic aortic rings to Ach in physiological situations, L-Arg-induced changes in the components of endothelial derived relaxation seems an important issue to be considered during L-Arg supplementation in the clinic.
Oner
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Akdeniz University, Medical Faculty, Department of Physiology, Antalya, Turkey. gulsen@med.akdeniz.edu.tr
Bilgen
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D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects*; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
D020030:Nitric Oxide Donors; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D009599:Nitroprusside; D010656:Phenylephrine; D001120:Arginine; D000109:Acetylcholine