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.

Non-invasive Assessment of Neurovascular Coupling After Aneurysmal Subarachnoid Hemorrhage: A Prospective Observational Trial Using Retinal Vessel Analysis

Objective: Delayed cerebral ischemia (DCI) is a common complication after aneurysmal subarachnoid hemorrhage (aSAH) and can lead to infarction and poor clinical outcome. The underlying mechanisms are still incompletely understood, but animal models indicate that vasoactive metabolites and inflammatory cytokines produced within the subarachnoid space may progressively impair and partially invert neurovascular coupling (NVC) in the brain. Because cerebral and retinal microvasculature are governed by comparable regulatory mechanisms and may be connected by perivascular pathways, retinal vascular changes are increasingly recognized as a potential surrogate for altered NVC in the brain. Here, we used non-invasive retinal vessel analysis (RVA) to assess microvascular function in aSAH patients at different times after the ictus.Methods: Static and dynamic RVA were performed using a Retinal Vessel Analyzer (IMEDOS Systems GmbH, Jena) in 70 aSAH patients during the early (d0−4), critical (d5−15), late (d16−23) phase, and at follow-up (f/u > 6 weeks) after the ictus. For comparison, an age-matched cohort of 42 healthy subjects was also included in the study. Vessel diameters were quantified in terms of the central retinal arterial and venous equivalent (CRAE, CRVE) and the retinal arterio-venous-ratio (AVR). Vessel responses to flicker light excitation (FLE) were quantified by recording the maximum arterial and venous dilation (MAD, MVD), the time to 30% and 100% of maximum dilation (tMAD30, tMVD30; tMAD, tMVD, resp.), and the arterial and venous area under the curve (AUCart, AUCven) during the FLE. For subgroup analyses, patients were stratified according to the development of DCI and clinical outcomes after 12 months.Results: Vessel diameter (CRAE, CRVE) was significantly smaller in aSAH patients and showed little change throughout the whole observation period (p < 0.0001 vs. control for all time periods examined). In addition, aSAH patients exhibited impaired arterial but not venous responses to FLE, as reflected in a significantly lower MAD [2.2 (1.0–3.2)% vs. 3.6 (2.6–5.6)% in control subjects, p = 0.0016] and AUCart [21.5 (9.4–35.8)%*s vs. 51.4 (32.5–69.7)%*s in control subjects, p = 0.0001] on d0−4. However, gradual recovery was observed during the first 3 weeks, with close to normal levels at follow-up, when MAD and AUCart amounted to 3.0 [2.0–5.0]% (p = 0.141 vs. control, p = 0.0321 vs. d5−15) and 44.5 [23.2–61.1]%*s (p = 0.138 vs. control, p < 0.01 vs. d0−4 & d5−15). Finally, patients with clinical deterioration (DCI) showed opposite changes in the kinetics of arterial responses during early and late phase, as reflected in a significantly lower tMAD30 on d0−4 [4.0 (3.0–6.8) s vs. 7.0 (5.0–8.0) s in patients without DCI, p = 0.022) and a significantly higher tMAD on d16−23 (24.0 (21.0–29.3) s vs. 18.0 (14.0–21.0) s in patients without DCI, p = 0.017].Conclusion: Our findings confirm and extend previous observations that aSAH results in sustained impairments of NVC in the retina. DCI may be associated with characteristic changes in the kinetics of retinal arterial responses. However, further studies will be required to determine their clinical implications and to assess if they can be used to identify patients at risk of developing DCI.Trial Registration:ClinicalTrials.gov Identifier: NCT04094155.

Differential pial and penetrating arterial responses examined by optogenetic activation of astrocytes and neurons

A variety of brain cells participates in neurovascular coupling by transmitting and modulating vasoactive signals. The present study aimed to probe cell type-dependent cerebrovascular (i.e., pial and penetrating arterial) responses with optogenetics in the cortex of anesthetized mice. Two lines of the transgenic mice expressing a step function type of light-gated cation channel (channelrhodopsine-2; ChR2) in either cortical neurons (muscarinic acetylcholine receptors) or astrocytes (Mlc1-positive) were used in the experiments. Photo-activation of ChR2-expressing astrocytes resulted in a widespread increase in cerebral blood flow (CBF), extending to the nonstimulated periphery. In contrast, photo-activation of ChR2-expressing neurons led to a relatively localized increase in CBF. The differences in the spatial extent of the CBF responses are potentially explained by differences in the involvement of the vascular compartments. In vivo imaging of the cerebrovascular responses revealed that ChR2-expressing astrocyte activation led to the dilation of both pial and penetrating arteries, whereas ChR2-expressing neuron activation predominantly caused dilation of the penetrating arterioles. Pharmacological studies showed that cell type-specific signaling mechanisms participate in the optogenetically induced cerebrovascular responses. In conclusion, pial and penetrating arterial vasodilation were differentially evoked by ChR2-expressing astrocytes and neurons.

Impact of Chronic Outward Force on Arterial Responses of Proximal and Distal of Long Superficial Femoral Artery Stent

Background Self-expanding nitinol stent (SENS) implantation is commonly oversized in the superficial femoral artery (SFA), and leads to chronic outward force (COF) and in-stent restenosis (ISR). This study aimed to investigate the impact of COF of oversizing SENS on ISR of SFA. Methods In patients with implanted SENS in SFA, intimal hyperplasia especially between proximal segment and distal segment was evaluated by quantitative angiography, and the impact of COF on mid-term angiographic outcomes was investigated. In addition, porcine model with implanted SENS was used to evaluate the impact of COF on angiographic and histopathologic outcomes at 1 month. Excised stented arteries were evaluated by histopathologic analysis. Results We analyzed 65 SENS in 61 patients with follow-up angiography at 6 months to 1 year. In the long SFA stent, stent-to-vessel ratio was significantly higher in the distal stent than in the proximal stent (1.3 ± 0.2 vs. 1.55 ± 0.25, P = 0.001). ISR incidence was higher at the distal stent (37.3% vs 52.6%, P = 0.029). After 4 weeks of SENS implantation in porcine model, restenosis % was 29.5 ± 12.9% versus 46.8 ± 21.5% (P = 0.016). The neointimal area was 5.37 ± 1.15 mm2 vs. 8.53 ± 5.18 mm2 (P = 0.05). The restenosis % was 39.34 ± 8.53% versus 63.97 ± 17.1% (P = 0.001). Conclusions The development of a tapered type stent for longer SFA lesion and the development of SENS with smaller diameter are necessary, particularly in Asians.

Exercise-induced vasodilation is not impaired following radial artery catheterization in coronary artery disease patients

Diagnosis and treatment for coronary artery disease (CAD) often involves angiography and/or percutaneous coronary intervention. However, the radial artery catheterization required during both procedures may result in acute artery dysfunction/damage. While exercise-based rehabilitation is recommended for CAD patients following catheterization, it is not known if there is a period when exercise may be detrimental due to catheter-induced damage. Animal studies have demonstrated exercise-induced paradoxical vasoconstriction postcatheterization. This study aimed to examine arterial responses to acute exercise following catheterization. Thirty-three CAD patients (65.8 ± 7.3 yr, 31.5 ± 6.3 kg/m2, 82% men) undergoing transradial catheterization were assessed before and 1 wk postcatheterization. Radial artery (RA) diameter and shear rate were assessed during handgrip exercise (HE), in both the catheterized (CATH) and control (CON) arms. Endothelial function was also assessed via simultaneous bilateral radial flow-mediated dilation (FMD) at both time points. We found that the increase in RA diameter and shear stress in response to HE ( P < 0.0001) was maintained postcatheterization in both the CATH and CON arms, whereas FMD following catheterization was impaired in the CATH [6.5 ± 3.3 to 4.7 ± 3.5% ( P = 0.005)] but not in the CON [6.2 ± 2.6 to 6.4 ± 3.5% ( P = 0.797)] limb. While endothelial dysfunction, assessed by FMD, was apparent 1 wk postcatheterization, the ability of the RA to dilate in response to exercise was not impaired. The impact of catheterization and consequent endothelial denudation on vascular dys/function in humans may therefore be stimulus specific, and a highly level of redundancy appears to exist that preserves exercise-mediated vasodilator responses. NEW & NOTEWORTHY Despite depressed flow-mediated endothelium-dependent dilation following catheterization-induced damage, radial artery responses to handgrip exercise were preserved. This suggests that arterial responses to catheterization may be stimulus specific and that redundant mechanisms may compensate for vasodilator impairment during exercise. This has implications for exercise-based rehabilitation after catheterization.