Background: Biomechanical remodeling of coronary resistance arteries in physiological left ventricular hypertrophy has not yet been analyzed, and the possible sex differences are unknown. Methods: Wistar rats were divided into four groups: male and female sedentary controls (MSe and FSe) and male and female animals undergoing a 12-week intensive swim training program (MEx and FEx). On the last day, the in vitro contractility, endothelium-dependent dilatation, and biomechanical properties of the intramural coronary resistance arteries were investigated by pressure microarteriography. Elastica and collagen remodeling were studied in histological sections. Results: A similar outer radius and reduced inner radius resulted in an elevated wall to lumen ratio in the MEx and FEx animals compared to that in the sedentary controls. The wall elastic moduli increased in the MEx and FEx rats. Spontaneous and TxA₂ agonist-induced tone was increased in the FEx animals, whereas endothelium-dependent relaxation became more effective in MEx rats. Arteries of FEx rats had stronger contraction, while arteries of MEx animals had improved dilation. Conclusions: According to our results, the coronary arterioles adapted to an elevated load during long-term exercise, and this adaptation depended on sex. It is important to emphasize that in addition to differences, we also found many similarities between the sexes in the adaptive response to exercise. The observed sport adaptation in the coronary resistance arteries of rats may contribute to a better understanding of the physiological and pathological function of these arteries in active and retired athletes of different sexes.

Background: We aimed to identify sex differences in the network properties and to recognize the geometric alteration effects of long-term swim training in a rat model of exercise-induced left ventricular (LV) hypertrophy. Methods: Thirty-eight Wistar rats were divided into four groups: male sedentary, female sedentary, male exercised and female exercised. After training sessions, LV morphology and function were checked by echocardiography. The geometry of the left coronary artery system was analysed on pressure-perfused, microsurgically prepared resistance artery networks using in situ video microscopy. All segments over > 80 μm in diameter were studied using divided 50-μm-long cylindrical ring units of the networks. Oxidative-nitrative (O-N) stress markers, adenosine A_2A and estrogen receptor (ER) were investigated by immunohistochemistry. Results: The LV mass index, ejection fraction and fractional shortening significantly increased in exercised animals. We found substantial sex differences in the coronary network in the control groups and in the swim-trained animals. Ring frequency spectra were significantly different between male and female animals in both the sedentary and trained groups. The thickness of the wall was higher in males as a result of training. There were elevations in the populations of 200- and 400-μm vessel units in males; the thinner ones developed farther and the thicker ones closer to the orifice. In females, a new population of 200- to 250-μm vessels appeared unusually close to the orifice. Conclusions: Physical activity and LV hypertrophy were accompanied by a remodelling of coronary resistance artery network geometry that was different in both sexes.

Background: Andropause and hypertension also increase the risk of coronary artery damage. Aim: To investigate the effect of testosterone deficiency and hypertension on intramural coronary vessels. Methods: 4 groups of 8-week-old Sprague-Dawley rats were studied: control male (Co, n=10), orchidectomized male (OCT, n=13), angiotensin (AII) hypertensive male (AII, n=10), and AII hypertensive and OCT (AII + OCT, n=8). Surgical orchidectomy was performed, and an osmotic minipump was inserted for chronic angiotensin II infusion (100 ng/min/kg). After 4 weeks, spontaneous tone and biomechanical properties of the intramural coronary resistance artery were investigated in vitro, by pressure microarteriography. Outcomes: Morphology and biomechanics of the intramural coronaries were evaluated: the outer diameter, wall thickness–to–lumen diameter ratio, and tangential wall stress in the contracted and relaxed states. Results: The outer diameter was reduced in OCT and AII + OCT groups (on 50 mmHg 315 ± 20 Co; 237 ± 21 OCT; 291 ± 16 AII, and 166 ± 12 μm AII + OCT). The increased wall thickness–to–lumen diameter ratio resulted in lower tangential wall stress in AII + OCT rats (on 50 mmHg 19 ± 2 Co; 24 ± OCT; 26 ± 5 AII, and 9 ± 1 kPa AII + OCT). Spontaneous tone was increased in the hypertensive rats (AII and AII + OCT groups) (on 50 mmHg 7.7 ± 1.8 Co; 6.1 ± 1.4 OCT; 14.5 ± 3.0 AII, and 17.4 ± 4.1 % AII + OCT). Clinical Implications: Andropause alone can be considered as a cardiovascular risk factor that will further exacerbate vascular damage in hypertension. Strengths & Limitations: A limitation of our study is that it was performed on relatively young rats, and the conclusions might not apply to coronary remodelling in older animals with slower adaptation processes. Conclusions: Testosterone deficiency and hypertension damage the mechanical adaptation of the vessel wall additively: double noxa caused inward eutrophic remodeling and increased tone.

Blood flow increases in arteries of the skeletal muscles involved in active work. Our aim was to investigate the gender differences as a result of adaptation to sport in the femoral arteries. Vascular reactivity and histology of animals were compared following a 12-week swimming training. Animals were divided into sedentary male (MS), trained male (MTr), sedentary female (FS), and trained female (FTr) groups. Isolated femoral artery rings were examined by wire myography. Contraction induced by phenylephrine (Phe) did not differ between the four groups. The contractile ability in the presence of indomethacin (INDO) was decreased in both sedentary groups. However, we found a specific cyclooxygenase-2 (COX-2) role only in FS rats. After exercise training, we observed increased vasoconstriction in both sexes, when nitro-L-arginine methyl ester (L-NAME) was present. The COX-dependent vasoconstriction effect disappeared in MTr animals, and the COX-2-dependent vasoconstriction effect disappeared in FTr ones. Relaxation was reduced significantly, when L-NAME was present in MTr animals compared to in FTr rats. The training was associated with greater endothelial nitric oxide synthase (eNOS) protein expression in males, but not in females. The present study proves that there are gender differences regarding adaptation mechanisms of musculocutaneous arteries to sports training. In males, relaxation reserve capacity was markedly elevated compared to in females.

Background: Chronic exercise has been linked to positive effects on cognitive function and brain health. The aim of our study was to investigate how exercise affects cerebral resistance artery morphology, with an underlying focus on potential sex differences. Methods: Wistar rats were divided into male exercising (M.Ex; n = 6), female exercising (F.Ex; n = 5), male sedentary (M.Sed; n = 5), and female sedentary (F.Sed; n = 5) groups. After a 12-week swimming program, histological examinations of the intracerebral and pial arterioles were performed. SMA-DAB (smooth muscle actin) and resorcin-fuchsin (elastica) stained brain coronal sections were used for quantitative colorimetric analysis. Results: Investigating the effect of exercise, we found that in both pial and intracerebral arterioles, the elastic fiber density increased in both female and male exercising animals compared to the sedentary groups (p < 0.05 (M.Sed vs. M.Ex); p < 0.0001 (F.Sed vs. F.Ex)). As sex differences, we found that in female animals’ pial arterioles, the density of elastic fiber was increased compared to the male exercising group (p < 0.001 (M.Ex vs. F.Ex)). In pial arterioles, the smooth muscle density was higher in the male sedentary animals (p < 0.01 (M.Sed vs. F.Sed)); in intracerebral arterioles, the smooth muscle density increased with exercise in the male animals as well (p < 0.0001 (M.Ex vs. F.Ex)). Conclusions: Our results demonstrate that the increase in vascular elasticity is more pronounced overall in female animals.

Chronic exercise induces functional adaptations in skeletal muscle microcirculation, but whether these are accompanied by sex-specific histological remodeling of arterioles remains unclear. This study examined gracilis muscle arterioles in trained (Ex) and sedentary (Se) female (F) and male (M) Wistar rats after a 12-week intensive swimming program (Mex = 6, FEx = 6; MSed = 6, FSed = 5). Histological remodeling was assessed by quantitative colorimetry analysis of resorcin-fuchsin (elastica; n = 661) and SMA-DAB (smooth muscle actin; n = 692) staining, focusing on elastic fiber density, internal elastic lamina (IEL) characteristics, and smooth muscle density in intramuscular and intermuscular vessels. Elastic fiber density and IEL thickness were generally greater in female animals than in males (p < 0.05). IEL staining intensity showed significant effects of sex (p = 0.043), exercise (p = 0.021), and a significant sex-by-exercise interaction (p = 0.037), with exercised females exhibiting the highest IEL staining intensity. Smooth muscle density did not differ significantly by sex or training status, although it was higher in intermuscular than intramuscular arterioles (p < 0.001), and increased with vessel diameter primarily in the intermuscular group. These findings demonstrate exercise-induced, sex-specific histological remodeling of skeletal muscle arterioles, primarily affecting elastic components, with more pronounced elastic adaptation in females.