Interactions between nitroglycerin and endothelium in vascular smooth muscle relaxation.
To evaluate the role of endothelium in nitroglycerin (NTG)-mediated vascular relaxation, epinephrine-contracted rat thoracic aortic segments with and without intact endothelium were exposed to NTG (10(-10) to 10(-5) M). Aortic segments with intact (endo+, n = 15) and denuded endothelium (endo-, n = 9) exhibited typical NTG-induced relaxation. However, the mean effective concentration of NTG was lower for endo- than for endo+ segments (P less than 0.001). To determine if this phenomenon related to nitric oxide (NO) generation by endothelium, six endo+ segments were treated with NG-monomethyl-L-arginine (L-NMMA), an inhibitor of NO production. These endo+ segments exhibited greater (P less than 0.001) relaxation in response to NTG than the untreated endo+ segments. Oxyhemoglobin, an inhibitor of guanylate cyclase activation, greatly diminished NTG-mediated relaxation of all aortic segments. To determine if the enhanced NTG-mediated relaxation of endo- segments was unique to the guanosine 3',5'-cyclic monophosphate-dependent vasodilator NTG, other endo+ and endo- segments were exposed to adenosine 3',5'-cyclic monophosphate-dependent vasodilator papaverine (10(-8) to 10(-4) M), and no difference in EC50 was noted between endo+ and endo- segments. Thus endothelium attenuates NTG-mediated vasorelaxation, and this attenuation is abolished by inhibition of endothelial NO production with L-NMMA. These observations indicate that endothelium is a dynamic modulator of vascular smooth muscle relaxant effects of NTG. This modulation appears to result from a competitive interaction between endothelial NO and NTG.
Dinerman
J L
JL
Department of Medicine, University of Florida College of Medicine, Gainesville.
Lawson
D L
DL
Mehta
J L
JL
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects*; D004837:Epinephrine / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D005996:Nitroglycerin / Q000494:pharmacology*; D010108:Oxyhemoglobins / Q000494:pharmacology; D010208:Papaverine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013482:Superoxide Dismutase / Q000494:pharmacology; D014661:Vasoconstriction; D014664:Vasodilation; D019323:omega-N-Methylarginine
D010108:Oxyhemoglobins; D019323:omega-N-Methylarginine; D001120:Arginine; D010208:Papaverine; D013482:Superoxide Dismutase; D005996:Nitroglycerin; D007213:Indomethacin; D004837:Epinephrine