A Single Simulated Heliox Dive Modifies Endothelial Function in the Vascular Wall of ApoE Knockout Male Rats More Than Females

Abstract

IntroductionThe number of divers is rising every year, including an increasing number of aging persons with impaired endothelial function and concomitant atherosclerosis. While diving is an independent modulator of endothelial function, little is known about how diving affects already impaired endothelium. In this study, we questioned whether diving exposure leads to further damage of an already impaired endothelium.MethodsA total of 5 male and 5 female ApoE knockout (KO) rats were exposed to simulated diving to an absolute pressure of 600 kPa in heliox gas (80% helium, 20% oxygen) for 1 h in a dry pressure chamber. 10 ApoE KO rats (5 males, 5 females) and 8 male Sprague-Dawley rats served as controls. Endothelial function was examined in vitro by isometric myography of pulmonary and mesenteric arteries. Lipid peroxidation in blood plasma, heart and lung tissue was used as measures of oxidative stress. Expression and phosphorylation of endothelial NO synthase were quantified by Western blot.Results and ConclusionA single simulated dive was found to induce endothelial dysfunction in the pulmonary arteries of ApoE KO rats, and this was more profound in male than female rats. Endothelial dysfunction in males was associated with changing in production or bioavailability of NO; while in female pulmonary arteries an imbalance in prostanoid signaling was observed. No effect of diving was found on mesenteric arteries from rats of either sex. Our findings suggest that changes in endothelial dysfunction were specific for pulmonary circulation. In future, human translation of these findings may suggest caution for divers who are elderly or have prior reduced endothelial function.

Endothelial dysfunction in small arteries and early signs of atherosclerosis in ApoE knockout rats

“…In a previous study on ApoE KO rats, we observed no increase in oxidative stress in the pulmonary artery of ApoE KO rats when assessed by lipid peroxidation in plasma. Moreover, we found that Tempol, a superoxide scavenger, did not affect endothelium-dependent relaxation 34 . However, in the previous study the rats were younger (6–9 weeks old) and fed a standard diet while in the current study, ApoE KO rats were fed a Western diet and developed significant hypercholesterolemia.…”

“…The pulmonary artery (first bronchial artery in right lobe) and third order mesenteric were dissected and mounted in an isometric myograph (Danish Myo Technology, Aarhus, Denmark) as described previously 34 . Maximal contractile response was assessed with potassium solution (KPSS): equimolar substitution of KCl for NaCl in PSS.…”

“…GraphPad Prism software (5.02 for Windows, LaJolla, California, USA) was used for data analysis, similar to previous studies 34 . The effects of inhibitors were calculated as a comparison of difference in concentration–response curves before and after administration of the drug.…”

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“…Diving causes endothelial dysfunction in humans and experimental animals, independently of other pathology such as DCS (Brubakk et al, 2005;Lambrechts et al, 2013). We recently showed that male ApoE KO rats as young as 6-9-weeks-old have greater endothelial dysfunction in their pulmonary arteries than Sprague Dawley rats after a similar simulated dive protocol (absolute pressure of 600 kPa and decompression of 50 kPa/min), due to altered NO-dependent signaling (Berenji Ardestani et al, 2019).…”

“…We have previously shown that a single simulated dive causes endothelial dysfunction in the pulmonary arteries of male ApoE knockout rats (Berenji Ardestani et al, 2019). Endothelial dysfunction in the pulmonary arteries of ApoE KO rats was associated with altered production or bioavailability of NO and was more profound in male than in female rats (Berenji Ardestani et al, 2019).…”