A published report of one of Dr Huk’s most recognised studies, featuring the role of nitric oxide in ischaemia, and the involvement of L-arginine and its importance in nitric oxide levels.
Background: L-Arginine-depleted environments accompanying ischaemia-reperfusion enhance superoxide production, leading to the formation of reactive oxygen species and a concomitant reduction in basal nitric oxide levels. The bioflavonoid quercetin may prevent these undesirable effects by scavenging superoxide.
Methods: Untreated rabbits were compared with those infused with quercetin (5 mg/kg for 2 min) during hindlimb ischaemia (2.5 h) and reperfusion (2 h). In both groups, nitric oxide concentration was measured (porphyrinic microsensor) in the femoral artery wall. Microvasculature changes (morphometry) and superoxide concentration (chemiluminescence) were measured intermittently in biopsies.
Results: Approximately 6 min into the period of ischaemia a rapid increase in nitric oxide level from a mean(s.e.m.) basal level of 50(20) to 450(30) nmol/l was observed. In untreated animals, nitric oxide concentration dropped to an undetectable level (less than 1 nmol/l) during reperfusion. In quercetin-treated animals, the decrease in nitric oxide concentration was slower, such that substantial amounts (60(20) nmol/l) accumulated during reperfusion. In biopsies after ischaemia-reperfusion maximal calcium ionophore A23187-stimulated nitric oxide concentration increased (25-30 per cent) in the presence of quercetin, while the superoxide concentration decreased.
Conclusion: Quercetin treatment mollified ischaemia-reperfusion injury to skeletal muscle by scavenging destructive superoxide and enhancing the cytoprotective nitric oxide concentration
(I Huk 1, V Brovkovych, J Nanobash Vili, G Weigel, C Neumayer, L Partyka, S Patton, T Malinski Br J Surg 1998 Aug;85(8):1080-5. doi: 10.1046/j.1365-2168.1998.00787.x. PMID: 9718001 DOI: 10.1046/j.1365-2168.1998.00787.x, British Journal of Surgery)