Prostaglandins and Radical Oxygen Species Are Involved in Microvascular Effects of Hyperoxia

Abstract

Hyperoxia causes vasoconstriction in most tissues, by mechanisms that are not fully understood. We investigated microvascular effects of breathing 100% oxygen in healthy volunteers, using iontophoresis to deliver acetylcholine (ACh) and sodium nitroprusside (SNP). Aspirin and vitamin C were used to test for involvement of prostaglandins and radical oxygen species. Forearm skin perfusion was measured using laser Doppler perfusion imaging. Results were analysed using dose-response modelling. The response to ACh was reduced by 30% during oxygen breathing compared to air breathing [0.98 (0.81–1.15) PU vs. 1.45 (1.30–1.60) PU, p < 0.001]. ED₅₀ values were unchanged [2.25 (1.84–2.75) vs. 2.21 (1.79–2.74), not significant]. Aspirin pre-treatment abolished the difference in response between oxygen breathing and air breathing [maximum: 1.03 (0.90–1.16) vs. 0.89 (0.77–1.01), not significant; ED₅₀: 1.83 (1.46–2.30) vs. 1.95 (1.65–2.30), not significant]. ACh-mediated vasodilatation during 100% oxygen breathing was partially restored after pre-treatment with vitamin C. Breathing 100% oxygen did not change the microvascular response to SNP [1.45 (1.28–1.62) vs. 1.40 (1.26–1.53), not significant]. These results favour the hypothesis that hyperoxic vasoconstriction is mediated by inhibition of prostaglandin synthesis. Radical oxygen species may be involved as vitamin C, independently of aspirin, partially restored ACh-mediated vasodilatation during hyperoxia.

Exploring the oxygen challenge test as a microcirculation evaluation model

“…The perfusion reduction effect of the oxygen supplementation has been known for several years, and is thought to be attributed not to sympathetic stimulation [26,27] but rather to the reactive oxygen species (ROS)-mediated inhibition of vasodilator prostanoid synthesis. [28] As expected, during oxygen breathing in the provocation phase, tc-pO 2 increased significantly, saturating hemoglobin and increasing its amount dissolved in plasma, thereby creating hyperoxia. In response to this increase, a vasoconstriction seemed to have occurred, which led to the statistically significant reduction of mbf.…”

Transdermal iontophoresis as an in-vivo technique for studying microvascular physiology

“…These effects make assessment of vasoconstrictor responses difficult to perform using laser Doppler based perfusion detectors. (Rousseau et al, 2010). …”

“…Despite conflicting evidence regarding the mechanisms by which the drug causes vasodilatation, ACh is commonly delivered iontophoretically to test endothelial function in a variety of clinical conditions, including diabetes (Arora et al, 1998;Cohen et al, 2008;Hannemann et al, 2002;Morris et al, 1995) , hypertension (Cupisti et al, 2000b;Farkas et al, 2004;Kellogg et al, 1998;Monostori et al, 2010), pre-eclampsia (Blaauw et al, 2005;Eneroth-Grimfors et al, 1993;Khan et al, 2005), Raynauds phenomenon (Anderson et al, 1996;Hettema et al, 2009;Khan and Belch, 1999), renal failure (Cupisti et al, 2000a), HIV (Monsuez et al, 2000) and heart failure (Andersson et al, 2005;Balmain et al, 2007). Also, it has been applied to investigate the effects of smoking (Pellaton et al, 2002), age (Rossi et al, 2002a), gender (Algotsson et al, 1995), hyperoxia (Rousseau et al, 2010;Yamazaki, 2007) and exercise (Lenasi and Strucl, 2004;Rossi et al, 2002b). …”

“…For instance, prostaglandins have been found to play a role in the endothelium-dependent, vasodilatory response to acetylcholine but also in the nonspecific response to iontophoretic current. Furthermore, the blunted response to acetylcholine seen during breathing of 100% oxygen is restored under aspirin pretreatment, indicating that the effect of hyperoxia on the endothelium-dependent vasodilatation involves prostaglandins (Rousseau et al, 2010). Similarly, the use of aspirin as an antagonist during iontophoresis of acetylcholine has suggested the involvement of prostanoids in altered endothelial function in women with Raynauds disease (Easter and Marshall, 2005).…”

Exploring human in vivo microcirculation with methyl nicotinate in different perfusion conditions

“…Despite of this effect, no statistical differences between parameters were found when the volunteer was breathing room air or oxygen, indicating that the MN-induced vasodilation mechanisms overpassed the hyperoxia-mediated blood flow reduction mechanisms. Recent studies reported different effects of hyperoxia on skin vasodilation mediated by different drugs [15,16] . However, none of these studies involved the application of MN.…”