Full-Face Mask Use during SCUBA Diving Counters Related Oxidative Stress and Endothelial Dysfunction

Impaired flow mediated dilation (FMD), an index of vascular stress, is known after SCUBA diving. This is related to a dysfunction of nitric oxide (NO) availability and a disturbance of the redox status, possibly induced by hyperoxic/hyperbaric gas breathing. SCUBA diving is usually performed with a mask only covering “half face” (HF) and therefore forcing oral breathing. Nasal NO production is involved in vascular homeostasis and, as consequence, can significantly reduce NO possibly promoting vascular dysfunction. More recently, the utilization of “full-face” (FF) mask, allowing nasal breathing, became more frequent, but no reports are available describing their effects on vascular functions in comparison with HF masks. In this study we assessed and compared the effects of a standard shallow dive (20 min at 10 m) wearing either FF or a HF mask on different markers of vascular function (FMD), oxidative stress (ROS, 8-iso-PGF2α) and NO availability and metabolism (NO2, NOx and 3-NT and iNOS expression). Data from a dive breathing a hypoxic (16% O2 at depth) gas mixture with HF mask are shown allowing hyperoxic/hypoxic exposure. Our data suggest that nasal breathing might significantly reduce the occurrence of vascular dysfunction possibly due to better maintenance of NO production and bioavailability, resulting in a better ability to counter reactive oxygen and nitrogen species. Besides the obvious outcomes in terms of SCUBA diving safety, our data permit a better understanding of the effects of oxygen concentrations, either in normal conditions or as a strategy to induce selected responses in health and disease.

Short-Term Treatment with Alirocumab, Flow-Dependent Dilatation of the Brachial Artery and Use of Magnetic Resonance Diffusion Tensor Imaging to Evaluate Vascular Structure: An Exploratory Pilot Study

Background: Short-term effects of alirocumab on vascular function have hardly been investigated. Moreover, there is a scarce of reliable non-invasive methods to evaluate atherosclerotic changes of the vasculature. The ALIROCKS trial was performed to address these issues using standard ultrasound-based procedures and a completely novel magnetic resonance-based imaging technique. Methods: A total of 24 patients with an indication for treatment with PCSK9 antibodies were recruited. There were 2 visits to the study site, the first before initiation of treatment with alirocumab and the second after 10 weeks of treatment. The key outcome measures included the change of carotid vessel wall fractional anisotropy, a novel magnetic resonance-based measure of vascular integrity, and the changes of carotid intima-media thickness and flow-dependent dilatation of the brachial artery measured with ultrasound. Results: A total of 19 patients completed the trial, 2 patients stopped treatment, 3 patients did not undergo the second visit due to the COVID pandemic. All of them had atherosclerotic vascular disease. Their mean (standard deviation) LDL-cholesterol concentration was 154 (85) mg/dL at baseline and was reduced by 76 (44) mg/dL in response to alirocumab treatment (p < 0.001, n = 19). P-selectin and vascular endothelial growth factors remained unchanged. Flow-dependent dilatation of the brachial artery (+41%, p = 0.241, n = 18), carotid intima-media thickness (p = 0.914, n = 18), and fractional anisotropy of the carotid artery (p = 0.358, n = 13) also did not significantly change. Conclusion: Despite a nominal amelioration for flow-dependent dilatation, significant effects of short-term treatment with alirocumab on vascular function were not detectable. More work would be needed to evaluate, whether fractional anisotropy may be useful in clinical atherosclerosis research.

Daily consumption of wild olive (acebuche) oil reduces blood pressure and ameliorates endothelial dysfunction and vascular remodelling in rats with L-NAME-induced hypertension

Purpose: Despite numerous reports on the beneficial effects of olive oil in the cardiovascular context, very little is known about the olive tree’s wild counterpart (Olea europaea, L. var. sylvestris), commonly known as acebuche (ACE) in Spain. The aim of this study was to analyse the possible beneficial effects of an extra virgin ACE oil on vascular function in a rodent model of arterial hypertension induced by L-NAME (NG-nitro-L-arginine methyl ester). Methods: Four experimental groups of male Wistar rats were studied: 1) normotensive rats (Control group); 2) normotensive rats fed a commercial diet supplemented with 15% (w/w) ACE oil (Acebuche group); 3) rats made hypertensive following administration of L-NAME (L-NAME group); and 4) rats treated with L-NAME and simultaneously supplemented with 15% ACE oil (LN+ACE group). All treatments were maintained for 12 weeks. Results: Besides a significant blood pressure-lowering effect, the ACE oil-enriched diet counteracted the alterations found in aortas from hypertensive rats in terms of morphology and responsiveness to vasoactive mediators. In addition, a decrease in hypertension-related fibrotic and oxidative stress processes was observed in L-NAME-treated rats subjected to ACE oil supplement. Conclusion: Using a model of arterial hypertension via nitric oxide depletion, here we demonstrate the beneficial effects of a wild olive oil based upon its vasodilator, antihypertensive, antioxidant, antihypertrophic and antifibrotic properties. We postulate that regular inclusion of ACE oil in the diet can alleviate the vascular remodelling and endothelial dysfunction processes typically found in arterial hypertension, thus resulting in a significant reduction of blood pressure.

Sex differences in rat renal arterial responses following exercise training

During aerobic exercise, hemodynamic alterations occure; while blood flow in skeletal muscle arteries increases, it decreases in visceral vessels due to mesenterial vasoconstriction. However, maintaining renal blood flow during intensive sport is also a priority. Our aim was to investigate the changes of vascular reactivity and histology of isolated renal artery of male and female rats in response to swim-training. Wistar rats were distributed into four groups: male sedentary (MSed), male trained (MTr), female sedentary (FSed), and female trained (FTr). Trained animals underwent a 12-week-long intensive swimming program. Vascular function of isolated renal artery segments was examined by wire myography. Phenylephrine-induced contraction was lower in FSed compared to MSed animals, and it was decreased by training in male but not in female animals. Inhibition of cyclooxygenases by indomethacin reduced contraction in both sedentary groups, and in MTr but not in FTr animals. Inhibition of nitric oxide production increased contraction in both trained groups. Acetylcholine induced relaxation was similar in all experimental groups showing predominant NO-dependency. Elastin and smooth muscle cell actin density was reduced in female rats after aerobic training. This study shows that, as a result of 12-weeks-long training, there are sex differences in renal arterial responses following exercise training. Swimming moderates renal artery vasoconstriction in male animals, while it depresses elastic fiber and smooth muscle actin density in females.

Prediction of High-Altitude Cardiorespiratory Fitness Impairment Using a Combination of Physiological Parameters During Exercise at Sea Level and Genetic Information in an Integrated Risk Model

Insufficient cardiorespiratory compensation is closely associated with acute hypoxic symptoms and high-altitude (HA) cardiovascular events. To avoid such adverse events, predicting HA cardiorespiratory fitness impairment (HA-CRFi) is clinically important. However, to date, there is insufficient information regarding the prediction of HA-CRFi. In this study, we aimed to formulate a protocol to predict individuals at risk of HA-CRFi. We recruited 246 volunteers who were transported to Lhasa (HA, 3,700 m) from Chengdu (the sea level [SL], &lt;500 m) through an airplane. Physiological parameters at rest and during post-submaximal exercise, as well as cardiorespiratory fitness at HA and SL, were measured. Logistic regression and receiver operating characteristic (ROC) curve analyses were employed to predict HA-CRFi. We analyzed 66 pulmonary vascular function and hypoxia-inducible factor- (HIF-) related polymorphisms associated with HA-CRFi. To increase the prediction accuracy, we used a combination model including physiological parameters and genetic information to predict HA-CRFi. The oxygen saturation (SpO2) of post-submaximal exercise at SL and EPAS1 rs13419896-A and EGLN1 rs508618-G variants were associated with HA-CRFi (SpO2, area under the curve (AUC) = 0.736, cutoff = 95.5%, p &lt; 0.001; EPAS1 A and EGLN1 G, odds ratio [OR] = 12.02, 95% CI = 4.84–29.85, p &lt; 0.001). A combination model including the two risk factors—post-submaximal exercise SpO2 at SL of &lt;95.5% and the presence of EPAS1 rs13419896-A and EGLN1 rs508618-G variants—was significantly more effective and accurate in predicting HA-CRFi (OR = 19.62, 95% CI = 6.42–59.94, p &lt; 0.001). Our study employed a combination of genetic information and the physiological parameters of post-submaximal exercise at SL to predict HA-CRFi. Based on the optimized prediction model, our findings could identify individuals at a high risk of HA-CRFi in an early stage and reduce cardiovascular events.

Capsaicin and Its Effect on Exercise Performance, Fatigue and Inflammation after Exercise

Capsaicin (CAP) activates the transient receptor potential vanilloid 1 (TRPV1) channel on sensory neurons, improving ATP production, vascular function, fatigue resistance, and thus exercise performance. However, the underlying mechanisms of CAP-induced ergogenic effects and fatigue-resistance, remain elusive. To evaluate the potential anti-fatigue effects of CAP, 10 young healthy males performed constant-load cycling exercise time to exhaustion (TTE) trials (85% maximal work rate) after ingestion of placebo (PL; fiber) or CAP capsules in a blinded, counterbalanced, crossover design, while cardiorespiratory responses were monitored. Fatigue was assessed with the interpolated twitch technique, pre-post exercise, during isometric maximal voluntary contractions (MVC). No significant differences (p > 0.05) were detected in cardiorespiratory responses and self-reported fatigue (RPE scale) during the time trial or in TTE (375 ± 26 and 327 ± 36 s, respectively). CAP attenuated the reduction in potentiated twitch (PL: −52 ± 6 vs. CAP: −42 ± 11%, p = 0.037), and tended to attenuate the decline in maximal relaxation rate (PL: −47 ± 33 vs. CAP: −29 ± 68%, p = 0.057), but not maximal rate of force development, MVC, or voluntary muscle activation. Thus, CAP might attenuate neuromuscular fatigue through alterations in afferent signaling or neuromuscular relaxation kinetics, perhaps mediated via the sarco-endoplasmic reticulum Ca2+ ATPase (SERCA) pumps, thereby increasing the rate of Ca2+ reuptake and relaxation.

Targeting Epigenetic Mechanisms in Vascular Aging

Environment, diseases, lack of exercise, and aged tendency of population have becoming crucial factors that induce vascular aging. Vascular aging is unmodifiable risk factor for diseases like diabetes, hypertension, atherosclerosis, and hyperlipidemia. Effective interventions to combat this vascular function decline is becoming increasingly urgent as the rising hospitalization rate caused by vascular aging-related diseases. Fortunately, recent transformative omics approaches have enabled us to examine vascular aging mechanisms at unprecedented levels and precision, which make our understanding of slowing down or reversing vascular aging become possible. Epigenetic viz. DNA methylation, histone modifications, and non-coding RNA-based mechanisms, is a hallmark of vascular aging, its deregulation leads to aberrant transcription changes in tissues. Epigenetics mechanisms by mediating covalent modifications to DNA and histone proteins, consequently, influence the sensitivity and activities of signaling pathways in cells and tissues. A growing body of evidence supports correlations between epigenetic changes and vascular aging. In this article, we will provide a comprehensive overview of epigenetic changes associated with vascular aging based on the recent findings with a focus on molecular mechanisms of action, strategies to reverse epigenetic changes, and future perspectives.

Ultrafast Doppler imaging and Ultrasound Localization Microscopy reveal the complexity of vascular rearrangement in chronic spinal lesion

Acute spinal cord injury (SCI) leads to severe damage to the microvascular network. The process of spontaneous repair is accompanied by formation of new blood vessels; their functionality, however, presumably very important for functional recovery, has never been clearly established, as most studies so far used fixed tissues. Here, combining ultrafast Doppler imaging and Ultrasound Localization Microscopy (ULM) on the same animals, we proceeded at a detailed analysis of structural and functional vascular alterations associated with the establishment of chronic SCI, both at macroscopic and microscopic scales. Using a standardized animal model of SCI, our results demonstrate striking hemodynamic alterations in several subparts of the spinal cord: a reduced blood velocity in the lesion site, and an asymmetrical hypoperfusion caudal but not rostral to the lesion. In addition, the worsening of many evaluated parameters at later time points suggests that the neoformed vascular network is not yet fully operational, and reveals ULM as an efficient in vivo readout for spinal cord vascular alterations. Finally, we show statistical correlations between the diverse biomarkers of vascular dysfunction and SCI severity. The imaging modality developed here will allow evaluating recovery of vascular function over time in pre-clinical models of SCI. Also, used on SCI patients in combination with other quantitative markers of neural tissue damage, it may help classifying lesion severity and predict possible treatment outcomes in patients.