Hyperbaric Oxygen Attenuates Aortic Vasoconstriction after Simulated Microgravity in Rats

Abstract

Background The hindlimb suspended (HLS) rat model has been used in land-based research to evaluate effects of simulated microgravity. Previous research demonstrated that 2-4 weeks of HLS reduced vasoconstrictive responses of aortic, mesenteric, and femoral arterial rings to phenylephrine (PHE) while acute exposure to hyperoxia amplified constrictive responses to PHE. The purpose of this study was to determine if hyperbaric oxygen treatment (HBO) during HLS would reverse the attenuation of the vasoconstrictive response. Methods Five-month-old male Sprague Dawley rats were randomly divided into aging controls (AC), AC-HBO, HLS, and HLS-HBO. Groups receiving HBO (AC-HBO; HLS-HBO) were placed in a cage that was fitted for the animal hyperbaric chamber to maintain HLS. HBO groups received 24 treatments, once a day, 6 d/week using a wound care protocol. The chamber was flushed with 100% oxygen, compressed over 10 min to 2.5 atmospheres absolute (ATA) (22.5 psig), a 90-minute treatment, then a 10 min decompression. After 28 d of HLS, animals were sacrificed under isoflurane anesthesia and thoracic aorta segments isolated. Relaxation of aortic rings was measured in response to acetylcholine (ACh) and sodium nitroprusside (SNP) after pre-constriction with PHE (3×10-7). Constriction of aortic rings was also determined in response to increasing concentrations of PHE. All drugs were administered cumulatively in vessel baths at 10-10-10-4 M. Data were analyzed using four-parameter (i.e., minimum, maximum, EC50, slope) nonlinear regression, and groups compared using 2×2 ANOVA with HBO and HLS as main effects. Results Responses to ACh and SNP were not affected by HLS or HBO. However, in response to PHE, there was a decrease in maximum vasoconstriction in HLS compared to controls (44.7±7.3% vs 82.4±6.0%, respectively, p≤0.05) and in HBO compared to controls (48.5±6.5% vs 78.6±6.8%, p≤0.05). Conclusion These results indicate that PHE-induced constriction of thoracic aorta is decreased after HLS. HBO did not reverse HLS-induced reductions in contractile responses; instead, HBO independently reduced PHE-stimulated constriction of aortic segments. This suggests that HBO may be useful in conditions where constriction is enhanced, such as diabetes.