A laser doppler study of the effect of 2-alkylthio-4-ethyl-4-methyl-4,5 dihydro-1H-imidazolin-5-one oxime (oxime) on the ischaemic rat lower limb.
The potential vasodilator effect of the novel compound 2-alkylthio-4-ethyl-4-methyl-4,5 dihydro-1H-imidazolin-5-one oxime (oxime) was investigated in a model of lower 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 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 lower 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 to 178.8, 328.9 and 705.9 %, respectively. Meanwhile, L-arginine given i.v. at 100 mg/kg increased BFR to 560 %. Isoprenaline given i.v. at 1 microg/kg increased BFR to 274.3 %, while isoprenaline combined with oxime (0.064 mg/kg) increased BFR to 402.7 %. Similarly, after topical application of oxime, BFR increased to 113.5, 261.1 and 433.3 %, respectively. L-arginine given at 1000 mg/kg increased BFR to 389.7 %. Isoprenaline given at 10 microg/kg increased BFR to 231.6 %, while isoprenaline administered in combination with oxime (0.064 mg/kg) increased BFR to 308.3 %. 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 1,000 mg/kg L-arginine, respectively. It is concluded that systemic or topical oxime results in marked enhancement of blood flow in the rat ischaemic lower limb. This effect of oxime is likely to be mediated through the release of NO.
Mostafa
R E
RE
Department of Pharmacology, National Research Centre, Cairo, Egypt.
Sleem
A A
AA
Abdel-Salam
O M E
OM
Ismail
M Abdel-Hamid
MA
Khalifa
A E
AE
D000818:Animals; D001120:Arginine / Q000494:pharmacology; D005121:Extremities / Q000098:blood supply*; D007511:Ischemia / Q000188:drug therapy* / Q000503:physiopathology; D007545:Isoproterenol / Q000494:pharmacology; D017078:Laser-Doppler Flowmetry; D008297:Male; D010091:Oximes / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014665:Vasodilator Agents / Q000627:therapeutic use*
D010091:Oximes; D014665:Vasodilator Agents; D001120:Arginine; D007545:Isoproterenol