The influence of endothelium on glyceryl trinitrate induced relaxation in corresponding arteries and veins of the rabbit.
Glyceryl trinitrate (GTN) induced relaxation was investigated in preparations of corresponding femoral arteries and veins from rabbits containing the intact endothelium in comparison to denuded vessels. Either vascular rings (app. 5 mm segments) or helical cut strips were isotonically mounted in organbaths (37 degrees C, Krebs-Henseleit-buffer). Vessels were precontracted with their specific EC-50 of norepinephrine. Cumulative concentration response curves for GTN were evaluated. Arteries and veins were dilated in a concentration dependent manner in the range of 1 nmol/l to 0.1 mmol/l. V.femoralis was the most sensitive vessel with an EC-50 of 10 nmol/l. There was no significant difference in the sensitivity of veins with or without endothelium. In contrast to this, for half-maximal relaxation of A. femoralis 2-3 orders of magnitude higher concentrations were necessary, depending on the presence of endothelium. The concentration ratio artery/vein (A/V) amounted to 800 in normal vessels, 100 in denuded vessels, resp. indicating that for half-maximal relaxation of endothelium containing arteries significant higher concentrations were needed. By preincubation for 60 min with the EC-90 of GTN in arteries, as well as in veins, tolerance could be induced independently of the presence of endothelium. However, veins were more affected than arteries, but tolerant veins were still more sensitive to GTN than tolerant arteries. This was true both for preparations with and without endothelium (A/V = 70 in normal vessels, 20 in denuded vessels, resp.). Moreover, the endothelial dependence of arterial relaxation was attenuated. Treatment of the tolerant vessels with cystein (1 mmol/l) did abolish the GTN-tolerance in veins but not in arteries.(ABSTRACT TRUNCATED AT 250 WORDS)
Rösen
R
R
Institut für Pharmakologie, Universität zu Köln, FRG.
Horn-Bosbach
M
M
König
E
E
Klaus
W
W
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D004730:Endothelium, Vascular / Q000187:drug effects*; D005263:Femoral Artery / Q000187:drug effects; D005268:Femoral Vein / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009569:Nitric Oxide / Q000378:metabolism / Q000502:physiology*; D005996:Nitroglycerin / Q000494:pharmacology*; D011817:Rabbits; D014655:Vascular Resistance / Q000187:drug effects*; D014664:Vasodilation / Q000187:drug effects*
D009569:Nitric Oxide; D005996:Nitroglycerin