Effect of temperature on glyceryl trinitrate induced relaxation of rabbit aorta.
It has previously been shown that the vasodilatory response to glyceryl trinitrate (GTN) was decreased during hypothermic cardiopulmonary bypass. The purpose of these experiments was to determine the effect of temperature on GTN-induced relaxation and on GTN biotransformation in rabbit aorta. It was determined that the EC50 of GTN on rabbit aortic rings (RARs) was increased significantly from 1.8 x 10(-8) M at 37 degrees C to 3.4 x 10(-8) M at 27 degrees C (p < 0.05). The production of NO by rabbit aortic strips (RASs) was significantly less at 27 degrees C compared with 37 degrees C after 80 min, being 9.62 x 10(-11) +/- 13.2 x 10(-11) mol NO/g wet wt. RASs compared with 5.71 x 10(-10) +/- 9.43 x 10(-11) mol NO/g wet wt. RASs, respectively (p < 0.05), after 80 min incubation. There was no difference in the amount of glyceryl-1,2-dinitrate (1,2-GDN) produced from GTN at the two temperatures. The ED20 for NO-induced relaxation of RARs increased from 3.46 x 10(-10) +/- 2.24 x 10(-10) mol at 37 degrees C to 1.01 x 10(-9) +/- 4.51 x 10(-10) mol at 27 degrees C (p < 0.05). These data indicate that the biotransformation of GTN and the release of NO were impaired by hypothermia, and that this, as well as a decrease in the tissue response to NO at 27 degrees C, explains the decrease in GTN activity at reduced body temperatures.
Booth
B P
BP
Department of Pharmacology and Toxicology, Faculty of Medicine, Queen's University, Kingston, ON, Canada.
Brien
J F
JF
Marks
G S
GS
Nakatsu
K
K
D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D001711:Biotransformation / Q000502:physiology; D003470:Culture Media; D006358:Hot Temperature; D066298:In Vitro Techniques; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D005996:Nitroglycerin / Q000031:analogs & derivatives / Q000378:metabolism / Q000493:pharmacokinetics*; D011817:Rabbits; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*; D014665:Vasodilator Agents / Q000378:metabolism
D003470:Culture Media; D014665:Vasodilator Agents; C014509:dinitroglycerol; D009569:Nitric Oxide; D005996:Nitroglycerin