Different sensitivities of arteries and veins to glyceryltrinitrate-induced relaxation and tolerance: an "in vitro" study on isolated vessels from rabbits.

Glyceryltrinitrate (GTN)-induced relaxation was examined in helical strips of rabbit femoral and mesenteric vessels after precontraction with norepinephrine (EC-50). Concentration-response curves over a wide concentration range (10(-9) to 3 X 10(-4) mol/l) appeared to be biphasic with a plateau at 10(-6) mol/l. Threshold concentrations for relaxation (EC-10) were different in arteries (2 X 10(-8) mol/l) and in veins (2 X 10(-9) mol/l), indicating a higher sensitivity of veins than of arteries to low concentrations of GTN. After induction of GTN-tolerance (60 min preincubation with EC-90) the arterial vessels revealed a monophasic concentration response curve (EC-10: 10(-6); EC-50: 10(-5) mol/l). The relaxation at the lower concentration range was abolished (shift to the right at lower GTN-concentration). On the other hand, in veins the concentration-response curve was completely shifted to higher concentrations (EC-10: 10(-8) mol/l) and the high sensitivity component was diminished to 50%. However, the enhanced sensitivity of veins in comparison to arteries was preserved. 10(-3) mol/l cystein was unable to affect tolerance in arteries, but partially reversed the development of tolerance effects in veins. Moreover, 10(-6) mol/l indomethacin could mimic GTN-tolerance in arteries but not in veins. Thus, relaxation as well as tolerance induced by GTN, seem to be mediated at least by 2 different mechanisms. Only in arteries the prostaglandin system appears to be involved. On the other hand depletion of SH-groups seems to play a major role in veins in agreement with the hypothesis of Ignarro et al. (1981).