Endogenous Carbon Monoxide Participates in Basal Perfusion Maintenance of Gingiva

Carbon monoxide (CO) is commonly recognized as an enviromental toxin that arises from an incomplete combustion of fossil fuels. However, it is also generated endogenously in the body from heme via heme oxygenase (HO) isoenzymes (inducible HO-1 also termed as heat shock protein-32 or constitutive HO-2) and involved in both physiological and pathological processes as a gaseous mediator. Objectives: The aim of our study was to investigate the effect of CO produced by HO on the gingival resting microcirculation. Methods: The gingival blood flow was measured by laser Doppler fluxmetry in the upper central papilla before (bsl) and after the application of an HO inhibitor (zinc deuteroporphyrin 2,4-bis glycol, ip. 45 micromol/kg) for 45 min in anaesthetized rats. The same study was repeated after the blockade of nitric oxide (NO) synthase activity (1mg/ml L-NAME in tap water ad libitum for 1 week). At the end of the experiments the HO isoenzymes were localized by immunohistochemistry in the gingival vessels. Results: HO inhibition significantly decreased gingival blood flow (GBF, bsl vs. 45. min: 570±94 vs. 326±85 BPU, p<0.05) and increased gingival vascular resistance (GVR, bsl vs. 45. min: 0.23±0.04 vs. 0.39±0.06 mmHg/BPU, p<0.05) without altering the mean arterial blood pressure (MBP). NO deficiency significantly increased the start-up MBP (control vs. L-NAME pretreatment: 108±3 vs. 145±4 mmHg, p<0.05) and GVR (control vs. L-NAME pretreatment: 0.23±0.04 vs. 0.35±0.04 mmHg/BPU, p<0.05) and prevented the vasoconstrictor effect of HO blockade in the gingiva. There was a weak HO-1 immunostaining within the vascular wall and the perivascular nerves elicited HO-2 reactivity. Conclusions: Our data indicate that endogenous CO is involved in the adequate maintenance of basal gingival perfusion. The vasodilatory effects of endogenous CO are NO dependent. Supports: OTKA T042584 and T049708.