ABSTRACT
The potential vasodilator effect of the novel compound 2-alkylthio-4-ethyl-4-methyl-4,5 dihydro-lH-imidazolin-5-one oxime [oxime] was investigated in a model of hind limb ischaemia induced in rats by unilateral ligation of the right femoral artery using Laser Doppler Flowmetry. The effect of oxime was compared with that of isoprenaline or L-arginine. Test drugs and oxime were injected systemically into the femoral vein or applied locally on the planter surface of the rat hind paw. Serum level of nitrite [NO[2] and nitrate [NO[3] were measured by ELISA. Immediately after operative induction of right hind limb ischaemia, blood flow ratio [Right/Left limb ratio: BFR] decreased to 0.33-0.39 in different groups. The intravenous [i.v.] administration of oxime increased BFR in a dose-dependent manner. Compared with pre-drug BFR, oxime administered at doses of 0.064, 0.128 or 0.256 mg/kg increased BFR by 78.8, 228.9 and 605.9%, respectively. Meanwhile, L-arginine given i.v. at 100 mg/kg increased BFR by 460%. Isoprenaline given i.v. at 1 micro g/kg increased BFR by 174.3%, while isoprenaline combined with oxime [0.064 mg/kg] increased BFR by 302.7%. Similarly, after topical application of oxime, BFR increased by 13.5, 161.1 and 333.3%, respectively. L-arginine given at 1000 mg/kg increased BFR by 389.7%. Isoprenaline given at 10 micro g/kg increased BFR by 131.6%, while isoprenaline administered in combination with oxime [0.064 mg/kg] increased BFR by 208.3%. The concentration of NO in serum was significantly increased after systemic or topical administration of either 0.128 and 0.256 mg/kg oxime or 100 and 1000 mg/kg L-arginine, respectively. It is concluded that systemic or topical oxime results in marked enhancement of blood flow in the rat ischaemic hind limb. This effect of oxime is likely to be mediated through the release of NO