The effect of nitroglycerin and chloropromazine (plegomazin) on norepinephrine-induced contraction of rat aorta rings is studied in experiments on the intact and deendothelized aorta, and the combined myolytic effect of the two preparations is assessed. A possible cross-tolerance between nitroglycerin and chloropromazine is studied in experiments simulating the development of vascular tolerance of nitroglycerin.
We used Fura-2 fluorometry to observe the effects of nitroglycerin (NG), isosorbide--2,5--dinitrate (ISDN) and sodium nitroprusside (NP) on basal and mitogen-induced (Con A, 25 micrograms/ml) cytoplasmic Ca++level ([Ca++]) in human blood lymphocytes. It is shown that nitrates dose-dependently decrease Con-A-induced increase in [Ca++]i. When compared for the effect on calcium metabolism, NP appeared most potent (IC50 = 4.1 x 10(-7) M). The drug action was not reported when the cells were exposed to Ca(++)-free solution. 120-min preincubation with 10(-4) M NG led to complete abolishment of the ISDN and NG effects. The results suggest that human lymphocytes may be used as an experimental model of nitrates action and mechanisms underlying tolerance to them.