Contribution of nitrergic nerve in canine gingival reactive hyperemia

Abstract

Reactive hyperemia reflects a compensatory vasodilation response of the local vasculature in ischemic tissue. The purpose of this study is to clarify the mechanism of regulation of this response in gingival circulation by using pharmacological analysis of reactive hyperemia and histochemical analysis of gingival tissue. Application of pressure to the gingiva was used to create temporary ischemia, and gingival blood flow was measured after pressure release. Reactive hyperemia increased in proportion to the duration of pressure. Systemic hemodynamics remained unaffected by the stimulus; therefore, the gingival reactive hyperemia reflected a local adjustment in circulation. Gingival reactive hyperemia was significantly suppressed by nitric oxide (NO) synthase inhibitors, especially the neural NO synthase-selective antagonist 7-nitroindazole, but not by anticholinergic drugs, β-blockers, or antihistaminergic drugs. Moreover, immunohistochemical staining for neural NO synthase and histochemical staining for NADPH diaphorase activity were both positive in the gingival perivascular region. These histochemical and pharmacological analyses show that reactive hyperemia following pressure release is mediated by NO-induced vasodilation. Furthermore, histochemical analysis strongly suggests that NO originates from nitrergic nerves. Therefore, NO may play an important role in the neural regulation of local circulation in gingival tissue ischemia.

Protective effects of (6R)-5,6,7,8-tetrahydro-L-biopterin on local ischemia/reperfusion-induced suppression of reactive hyperemia in rat gingiva

“…These results indicated that NO played a major role in RH as a non-cholinergic, non-adrenergic, and non-histaminergic regulatory agent. ( 2 , 3 ) Previous findings obtained in dog gingiva were consistent with our results on the suppression of rat gingival RH. Toda et al ( 20 ) showed that the nitrergic nerve acted as a vasodilator.…”

“…We previously demonstrated using NO electrodes that NO directly played a role in dog gingival RH; the NO current was slowly elevated in dog gingival tissues during ischemia. ( 2 ) RH subsequently occurred in parallel with a marked elevation in the NO current. RH was not affected by cholinergic blocking agents, adrenergic blocking agents, or antihistaminic agents, and was markedly suppressed by l -NAME.…”

“…We previously demonstrated that nitric oxide (NO) was a mediator of postcompression-reperfusion RH in dog gingiva. ( 2 , 3 ) A relationship between NO and RH has been reported in tissues and organs other than those in the oral cavity region (for example, the extremities, heart, and brain). ( 4 – 6 ) NO is produced from l -arginine as a substrate by nitric oxide synthase (NOS).…”

Evidence of spreading vasodilation in the human gingiva evoked by nitric oxide

“…There are several animal studies demonstrating that the endothelial or neuronal release of NO has a fundamental role in both the maintenance and the regulation of gingival blood flow (GBF) in reactive hyperaemia as well as in the pathophysiology of periodontitis . Endothelial and inducible nitric oxide synthases were found in human gingival tissue, but direct evidence of the contribution of NO to the regulation of human GBF has not been demonstrated yet.…”

“…9,10 It is observed in several tissues such as the lymphatics, 11 the intestines, 12 the skeletal muscles, [13][14][15] the brain, 16,17 the kidneys 18,19 and the mesentery. 20 There are several animal studies demonstrating that the endothelial or neuronal release of NO has a fundamental role in both the maintenance and the regulation of gingival blood flow (GBF) [21][22][23][24] in reactive hyperaemia 25,26 as well as in the pathophysiology of periodontitis. [27][28][29] Endothelial and inducible nitric oxide synthases were found in human gingival tissue, 27,[29][30][31] but direct evidence of the contribution of NO to the regulation of human GBF has not been demonstrated yet.…”