BACKGROUND . Changes in the human nutrition profile have led to excessive consumption of fats and carbohydrates, which is accompanied by the development of metabolic syndrome (MS). The main studies of the mechanisms of MS are performed on males, the features of MS in females have not been sufficiently studied. OBJECTIVE . The objective was to assess the state of lipid and carbohydrate metabolism, the functional state of the mesenteric arteries in intact and ovariectomized female Wistar rats under a high-fat dietary load. MATERIALS AND METHODS . Four groups of female rats were used: HFD (high fat diet, n=14), intact, receiving 50% fat in the diet, HFD (n=14) — ovariectomized, receiving 50% fat, CG (n=12) — intact, receiving a standard diet, OvCG (n=12) — ovariectomized, receiving a standard diet. After 10 weeks, the responses of mesenteric arteries precontracted with phenylephrine to acetylcholine (ACh) in the absence and with the use of an NO synthase blocker (L-NAME), as well as to sodium nitroprusside (NP), were studied using microphoto- and video recording of the vessel diameter in vivo. The state of carbohydrate and lipid metabolism, arterial pressure (BP), and the level of visceral obesity were assessed. The study refers to an interventional single-sample controlled study. RESULTS . In the absence of differences in body weight in HFD and OvHFD rats, excess fat intake leads to visceral obesity, increased triglyceride and LDL levels, increased blood pressure, and insulin resistance compared to CG and OvCG. Evaluation of mesenteric artery dilation at an ACh concentration of 10–5 mol/L showed that in HFD females the relaxation amplitude was 19.9% lower than in CG, and in OvHFD it was 21.3% lower than in OvCG. Compared with the magnitude of dilation on ACh without blockers, pre-incubation of vessels with L-NAME led to a decrease in the amplitude of ACh-induced vascular relaxation in CG by 68.0±3.6%, in OvCG by 70.1±3.4%, in HFD by 48.4±2.9%, in OvHFD by 55.1±3.9%. NP-induced vasodilation was reduced in HFD rats by 32.3%, in OvHFD by 32.2% compared with CG and OvCG. CONCLUSION . Excessive fat consumption by female rats is accompanied by visceral obesity, increased blood pressure, dyslipidemia, and impaired carbohydrate metabolism, dyslipidemia. The development of MS is accompanied by endothelial dysfunction, manifested by a decrease in ACh-induced dilation due to both the suppression of NO production by the endothelium and a decrease in the sensitivity of SMC to NO, while in ovariectomized females, visceral obesity without a decrease in vascular reactivity compared to intact animals.

The impact of the T786C and Glu298Asp polymorphisms of the NOS3 gene on vascular reactivity parameters was assessed in patients with coronary artery disease and type 2 diabetes mellitus. Ninety-two patients were examined and genotyping was performed using PCR. Average linear blood flow velocity, arterial diameters before and after the functional test, and resistance and reactivity coefficients were studied. A significant decrease in vascular reactivity was found in carriers of the T/C and Glu/Asp genotypes compared to homozygotes. The identified patterns highlight the importance of NOS3 polymorphisms in the pathogenesis of vascular disorders in the combination of coronary heart disease and type 2 diabetes.

The changes in brain function in response to mild head injury are usually subtle and go undetected. Physiological biomarkers would aid in the early diagnosis of mild head injury. In this study we used hypercapnia to follow changes in cerebral vascular reactivity after repetitive mild head injury. We hypothesized head injury would reduce vascular reactivity. Rats were maintained on a reverse light-dark cycle and head impacted daily at 24 h intervals over three days. All head impacts were delivered while rats were fully awake under red light illumination. There was no neuroradiological evidence of brain damage. After the 3rd impact rats were exposed to 5% CO2 and imaged for changes in BOLD signal. All imaging was done while rats were awake without the confound of anesthesia. The data were registered to a 3D MRI rat atlas with 171 segmented brain areas providing site specific information on vascular reactivity. The changes in vascular reactivity were not uniform across the brain. The prefrontal cortex, somatosensory cortex and basal ganglia showed the hypothesized decrease in vascular reactivity while the cerebellum, thalamus, brainstem, and olfactory system showed an increase in BOLD signal to hypercapnia.Supplementary InformationThe online version contains supplementary material available at 10.1007/s00221-024-06907-7.

Chronic kidney disease is accompanied by cardiovascular complications, including endothelial dysfunction, arterial hypertension, and atherosclerosis. The aim of this work is to compare the reactivity of the vessels of the microcirculatory bed (MCR) of the skin, assessed by laser Doppler flowmetry (LDF) and mesenteric arteries in rats with resection of 5/6 of the mass of the kidneys, and to evaluate the possibility of using LDF analysis as a method that reflects the functional state of large resistive vessels. Wistar rats were divided into two groups: animals of the NE-group (n = 15) had 5/6 of the mass of kidney tissue removed, control animals of the SO-group (n = 15) underwent a sham operation. After 8 weeks, the reactivity of rat skin microvessels to acetylcholine (ACh) and sodium nitroprusside (NP) iontophoresis was assessed. A week later, in rats, the effect of NE on the reactivity of mesenteric arteries preconstricted with phenylephrine was evaluated in vivo using microphotographic and video recording of the diameter. It has been shown that NE does not affect the average value of perfusion in the skin of rats at rest, however, it changes the structure of the frequency range of the spectrum of fluctuations in the MCR index, increasing the value of endothelial, neurogenic, and myogenic tone. NE led to the development of endothelial dysfunction of the mesenteric arteries and MCR vessels of the skin, which was expressed in a decrease in vascular reactivity to the action of endothelium-dependent (ACh) and endothelium-independent (NP) vasodilators. Thus, the development of experimental kidney dysfunction led to changes in the spectral components of fluctuations in the MCR index in the skin, indicating an increase in tonic effects of various genesis on the vessels. NE was accompanied by a decrease in the reactivity of microvessels of the skin and mesenteric arteries, however, there was no correlation between an increase in the MCR index and dilatation of the mesenteric arteries under the action of vasodilator agonists.

The carotid body has been implicated as an important mediator and putative target for hypertension. Previous studies have indicated an important role for angiotensin II in mediating carotid body function via angiotensin type-1 receptors (AT1R); however, their role in modulating carotid body function during hypertension is unclear. Using a large preclinical ovine model of renovascular hypertension, we hypothesized that acute AT1R blockade would lower blood pressure and decrease carotid body-mediated increases in arterial pressure. Adult ewes underwent either unilateral renal artery clipping or sham surgery. Two weeks later, flow probes were placed around the contralateral renal and common carotid arteries. In both hypertensive and sham animals, carotid body stimulation using potassium cyanide caused dose-dependent increases in mean arterial pressure but a reduction in renal vascular conductance. These responses were not different between groups. Infusion of angiotensin II led to an increase in arterial pressure and reduction in renal blood flow. The sensitivity of the renal vasculature to angiotensin II was significantly attenuated in hypertension compared with the sham animals. Systemic inhibition of the AT1R did not alter blood pressure in either group. Interestingly carotid body-evoked arterial pressure responses were attenuated by AT1R blockade in renovascular hypertension but not in shams. Taken together, our findings indicate a decrease in vascular reactivity of the non-clipped kidney to angiotensin II in hypertension. The CB-evoked increase in blood pressure in hypertension is mediated in part, by the AT1R. These findings indicate a differential role of the AT1R in the carotid body versus the renal vasculature.

Ipomoea hederacea Jacq.: A plant with promising antihypertensive and cardio-protective effects

Total sleep deprivation (TSD) is associated with endothelial dysfunction and a consequent decrease in vascular reactivity and increase in peripheral vascular resistance. These effectors compromise the body's ability to thermoregulate in hot and cold stress conditions. We investigated heat-unacclimated young adult men (26±2years) to determine whether 36hr of TSD compared to an 8 or 4-hr sleep condition, would suppress the responses of the autonomic system (body rectal temperature [Tre ], heart rate [HR], root mean square of successive interbeat intervals, physiological strain, blood pressure [BP], circulating blood catecholamines, sweating rate and subjective sensations) to whole-body uncompensable passive heat stress in traditional Finnish sauna heat (Tair =80-90°C, rh=30%). Sauna bathing that induced whole-body hyperthermia had a residual effect on reducing BP in the 8-hr and 4-hr sleep per night conditions according to BP measurements. By contrast, 36hr of total wakefulness led to an increase in BP. These observed sleep deprivation-dependent differences in BP modifications were not accompanied by changes in the blood plasma epinephrine and norepinephrine concentrations. However, during sauna bathing, an increase in BP following 36hr of TSD was accompanied by significant decreases in body Tre , HR and physiological strain, together with a diminished sweating rate, enhanced vagus-mediated autonomic control of HR variability, and improved thermal perception by the subjects. Our results suggest the impaired ability of the body to accumulate external heat in the body's core under uncompensable passive heat conditions following 36hr of TSD, because of the TSD-attenuated autonomic system response to acute heat stress.

In Vitro Effects of Eicosapentaenoic and Docosahexaenoic Acid on the Vascular Tone of a Human Saphenous Vein: Influence of Precontractile Agents

The aim : to evaluate changes in endothelium-dependent regulation of the tone of blood vessels (aorta and superior mesenteric artery) in rats 4 months after the removal of 5/6 renal tissue. Material and methods. An experimental CKD model was created by resection of 5/6 mass of renal tissue. The experimental group included animals (n = 12), subjected to nephrectomy (NE). The control group consisted of sham-operated (SO) rats (n = 10). Researches of vascular reactivity were performed on ring segments 2 mm long, which were excised from the aorta and superior mesenteric artery (SMA). A total of 23 segments of the aorta and 17 segments of SMA from rats after NE and 18 segments of the aorta and 15 segments of SMA from control animals were prepared. To measure the strength of contractions of the drugs, a FORT-10 sensor (WPI, USA) was used. The effects of acetylcholine (Ach, 1 x10 -6 M) on blood vessels, previously exposed to phenylephrine (1 x10 -5 M), and the response of vessels to Ach under conditions of prior exposure to TEA (1 x 10 -3 mol / l) and L-NAME (1 x10 -4 mol / l) were evaluated. Results. NE for a period of 4 months led to arterial hypertension - BP in the NE group of rats was higher (165, 0 ± 9.8 mm Hg) compared with SO (127.2 ± 9.7 mm Hg, р <0,001), and to myocardial remodeling (LVMI in NE rat was 2.72 ± 0.11 mg / g compared to 2.35 ± 0.09 mg / in the SO group, р <0,001 ). NE led to a decrease in dilatation of aortic and BWA fragments on the ACh compared with LO animals. Under the conditions of NO blocking, the NO synthase inhibitor — L-NAME — also had a lower response to ACh in rats with NE. The preliminary blockade of the Ca2 + -activated K + channels of high conductivity with the introduction of TEA resulted in a decrease in vasodilation caused by ACh in NE rat compared with the SO group. Conclusion. Resection of 5/6 of the kidney tissue mass in rats causes a decrease in vascular reactivity on the ACh. Endothelial dysfunction of rats after NE is associated with impairment of both NO-related and hyperpolarization-dependent endothelial cells in pathways of the vascular tone regulation.

Hemorrhagic shock-induced changes in vascular reactivity appear organ-specific. In the present study, we examined the hypothesis that vascular reactivity induced by septic shock similarly displays organ-specific differences and is regulated by inducible nitric oxide synthase (iNOS) and endothelin-1 (ET-1). Endotoxic shock was induced in rabbits by administration of lipopolysaccharide (LPS) (1 mg/kg), and organ specificity of vascular reactivity of superior mesenteric artery (SMA), celiac artery (CA), and left renal artery (LRA) as well as the potential involvement of iNOS and ET-1 examined. Vascular reactivity of SMA, CA, and LRA was increased at the early stages and decreased at the late stages after LPS administration. Superior mesenteric artery showed the greatest decrease in vascular reactivity in response to norepinephrine (NE) (34.9%) and acetylcholine (Ach; 32.3%), followed by LRA (NE, 33.7%; Ach, 30.5%) and CA (NE, 16.2%), whereas the relaxation reactivity of CA in response to Ach was increased to 159%. The mRNA and protein levels of iNOS and ET-1 in SMA, CA, and LRA were not affected at the early stages of endotoxic shock after LPS administration but significantly increased at the late stages. Expression levels were higher in SMA than CA and LRA and negatively correlated with the decrease in vascular reactivity. The iNOS and ET-1 inhibitors, aminoguanidine (20 mg/kg) and PD-142893 (0.02 mg/kg), respectively, induced significant improvements in vascular reactivity and organ perfusion and stabilized the hemodynamic parameters in rabbits subjected to endotoxic shock. Changes in vascular reactivity during endotoxic shock are organ-specific. Differential expression patterns of iNOS and ET-1 in different blood vessels contribute to the organ specificity of vascular reactivity. Therapeutic study, level II.

Anti-oxidative treatment with vitamin E improves peripheral vascular function in patients with diabetes mellitus and Haptoglobin 2-2 genotype: A double-blinded cross-over study.

It has been proposed that sympathoexcitation is responsible for vascular desensitization to α1‐adrenoceptor stimulation during lipopolysaccharide (LPS)‐induced systemic inflammation. The present study tested this hypothesis by examining the effects of sympatho‐deactivation with the α2‐adrenoceptor agonist, dexmedetomidine, on mean arterial pressure (MAP), renal sympathetic nerve activity (RSNA), and vascular reactivity to phenylephrine in conscious rats with cardiac autonomic blockade (methylatropine and atenolol) following LPS administration. In male, adult Sprague‐Dawley rats (n = 5 per group), RSNA and MAP were continuously recorded over 1‐h periods, before and after LPS administration (20 mg/kg iv), and finally after infusion of either saline or dexmedetomidine (5 μg/kg, then 5 μg/kg/h iv). A full dose–response curve to phenylephrine was constructed under each condition. After pooling data from both groups of rats (n = 10), LPS significantly (P = 0.005) decreased MAP (from 115 ± 1 to 107 ± 2 mmHg), increased RSNA (to 403 ± 46% of baseline values) and induced 4 to 5‐fold increases in the half‐maximal effective dose (ED50) of phenylephrine (from 1.02 ± 0.09 to 4.76 ± 0.51 μg/kg). During saline infusion, RSNA progressively decreased while vascular reactivity did not improve. Treatment with dexmedetomidine decreased MAP, returned RSNA to near pre‐endotoxemic levels, but only partially restored vascular reactivity to phenylephrine (ED50 was still threefold increased as compared with baseline values). These findings indicate that only part of the decrease in vascular reactivity to α1‐adrenoceptor stimulation during endotoxemia can be accounted for by sympathetic activation, at least on a short‐term basis.

The current diagnosis and treatment guidelines for severe trauma and shock are all for healthy population. Few studies focused on the pathophysiological features and treatments in metabolic diseases after severe trauma and shock. Vascular reactivity is significantly decreased after severe trauma and shock. Improving the vascular reactivity with arginine vasopressin (AVP) and phorbol-12 myristate-13-acetate (PMA) is beneficial to trauma and shock. Whether the cardiovascular function and treatment responses have the own features in hypertensive, diabetic, and hyperlipidemic patients after traumatic hemorrhagic shock is not known. Using hypertensive, diabetic, and hyperlipidemic and healthy rats, we compared the change patterns in cardiovascular function including vascular reactivity, tissue perfusion, and the hemodynamics after hemorrhagic shock and their responses to AVP, PMA, and common antishock agents including dopamine and norepinephrine. A same degree of hemorrhagic shock (40% hemorrhage or mean arterial pressure maintained at 40 mm Hg for 2 h) resulted in a more obvious decrease in vascular reactivity, hemodynamics, tissue perfusion, and mitochondrial function of liver and kidney in hypertensive, diabetic, and hyperlipidemic rats, and a more rapidly natural death than in healthy rats. The effectiveness of AVP and PMA in these diseased rats was lower than in healthy rats. The effective dosage of common antishock agents including norepinephrine, dopamine, and AVP in healthy rats was wider than that in these diseased rats. Among the antishock agents used in the current study, AVP had the best effect in improving animal survival and vascular reactivity both in healthy and in diseased rats. These findings suggest that hypertensive, diabetic, and hyperlipidemic rats have a worse vascular reactivity and organ function than the healthy rats after traumatic hemorrhagic shock, which result in the worse treatment responses and effects to vasoactive agents. Lower dose of AVP can be recommended as the first-line antishock agents for these diseased rats.

Background: Ozone therapy is a form of complementary medicine treatment that aims to increase the amount of oxygen to the body through the introduction of ozone into the body. Objective: Studying the effects of diabetes mellitus, insulin and ozone on ischemic reperfusion (IR) injury on the heart and vascular reactivity in diabetic rat. Material and Methods: Two hundred and fifty adult male albino rats of local strain, weighing 120-150 ±10 grams each, were used in this investigation and divided into: Group I (Normal control group): 10 rats. Group II (Diabetic group -240 rats) were subdivided into 4 subgroups: Group II-a (Diabetic non-treated group - 40 rats), Group II-b (Diabetic insulin-treated group - 40 rats, and Group II-c (Diabetic ozone-treated group - 80 rats Group II-d (Diabetic ozone and insulin-treated group - 80 rats): Rats were submitted to ozone therapy with concomitant treatment with insulin. Supernatant serum was collected in a dry clean tube for estimation of fasting serum glucose, serum total cholesterol, triglycerides, HDL, LDL, LDH, catalase enzyme, glutathione peroxidase, and SOD. Rat aortic rings preparation were used for estimation of changes in vascular reactivity in response to norepinephrine (10-5), vasopressin (10-6 M), indomethacin (10-6 M) and relaxation of aortic rings (preconstricted by NE (10-5) in response to ACh (10-6) and Na+ nitroprusside (10-6) as estimated in different groups. The organ bath was washed out three times with fresh Krebs' solution before the next substance was added and the rings were allowed to stabilize for 1 hour. All results were presented as the mean ± SEM. The data were analyzed using SPSS program version 12. For comparison of statistical significance between different groups, a one way ANOVA with the post hoc of Tukey's multiple comparison test was used. A value of P ≤ 0.05 was considered statistically significant. Results: Ozone therapy caused significant decrease in fasting glucose, total cholesterol, triglycerides, LDL, and lactate dehydrogenase “LDH”, and significant increase in HDL and myocardial antioxidants (catalase, superoxide dismutase “SOD” and glutathione peroxidase). There were a significant increase in cardiac contractility and heart rate during pre-ischemic and ischemic periods. There was a significant decrease in heart rate accompanied by significant increase in cardiac contractility during reperfusion period. Also, ozone treatment produced a significant decrease in vascular reactivity of aortic rings to norepinephrine, vasopressin and indomethacin, with significant increase in percentage of relaxation to acetyl choline “ACh”. Conclusion: Diabetic complications are attributed to the oxidative stress in the body. Ozone activates the antioxidant system affecting the level of glycemia. Ozone prevents oxidative stress by normalizing the organic peroxide levels by activating superoxide dismutase.

Hyperhomocysteinemia induces vascular endothelial dysfunction, an early hallmark of atherogenesis. While higher levels of circulating asymmetric dimethylarginine (ADMA) and symmetric dimethyl arginine (SDMA), endogenous inhibitors of nitric oxide synthesis, have been associated with increased cardiovascular risk, the role that ADMA and SDMA play in the initiation of hyperhomocysteinemia-induced endothelial dysfunction remains still controversial. In the present study, we studied the changes of circulating ADMA and SDMA in a rat model of acutely hyperhomocysteinemia-induced endothelial dysfunction. In healthy rats, endothelium-related vascular reactivity (measured as acetylcholine-induced transient decrease in mean arterial blood pressure), plasma ADMA and SDMA, total plasma homocysteine (tHcy), cysteine and glutathione were measured before and 2, 4 and 6 h after methionine loading or vehicle. mRNA expression of hepatic dimethylarginine dimethylaminohydrolase-1 (DDAH1), a key protein responsible for ADMA metabolism, was measured 6 h after the methionine loading or the vehicle. Expectedly, methionine load induced a sustained increase in tHcy (up to 54.9 ± 1.9 µM) and a 30 % decrease in vascular reactivity compared to the baseline values. Plasma ADMA and SDMA decreased transiently after the methionine load. Hepatic mRNA expression of DDAH1, cathepsin D, and ubiquitin were significantly lower 6 h after the methionine load than after the vehicle. The absence of an elevation of circulating ADMA and SDMA in this model suggests that endothelial dysfunction induced by acute hyperhomocysteinemia cannot be explained by an up-regulation of protein arginine methyltransferases or a down-regulation of DDAH1. In experimental endothelial dysfunction induced by acute hyperhomocysteinemia, down-regulation of the proteasome is likely to dampen the release of ADMA and SDMA in the circulation.

Early changes in vascular reactivity in response to 56Fe irradiation in ApoE–/– mice

Effects of Kaempferia parviflora rhizomes dichloromethane extract on vascular functions in middle-aged male rat

Several medical conditions exhibit age- and sex-based differences. Whether or not traumatic shock exhibits such differences with regard to vascular responsiveness is not clear. In a cohort of 177 healthy subjects and 842 trauma patients (21-82 years) as well as different ages (4, 8, 10, 14, 18, and 24 wk; 1 and 1.5 years) and sexes of Sprague-Dawley normal and traumatic shock rats, the age- and sex-based differences of vascular responsiveness and the underlying mechanisms were investigated. Middle-aged and young women as well as female rats of reproductive age had higher vascular responsiveness in the normal condition and a lower decrease in vascular responsiveness after traumatic shock than older men and male rats of identical age. Exogenous supplementation of 17β-estrdiol increased vascular reactivity in both male and femal rats of 8-24 wk and preserved vascular responsiveness in rats following traumatic shock. No effect was observed in rats 1 to 1.5 years. These protective effects of estrogen were closely related to G protein-coupled receptor (GPR)30, estrogen receptor-mediated Rho kinase, and PKC pathway activation. Vascular responsiveness exhibits age- and sex-based differences in healthy subjects and trauma patients. Estrogen and its receptor (GPR30) mediated activation of Rho kinase and PKC using genomic and nongenomic mechanisms to elicit protective effects in vascular responsiveness. This finding is important for the personalized treatment for several age- and sex-related diseases involving estrogen.

Late preterm infants: lung and brain development

Vascular reactivity shows biphasic changes after severe trauma or shock. Our aim was to elucidate the mechanisms of biphasic-changed vascular reactivity after haemorrhagic shock by observing the regulation of angiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2) on it. Haemorrhagic-shock Sprague-Dawley rats, hypoxia-treated superior mesenteric arteries (SMAs) with intact endothelia, and a cell mixture of vascular smooth muscle cells (VSMCs) and vascular endothelial cells (VECs) were adopted to evaluate the regulatory effects of Ang-1 and Ang-2 on vascular reactivity and their relationship to Tie2 (receptor tyrosine kinase)-Akt-endothelial nitric oxide synthase (eNOS) and Tie2-extracellular signal-regulated kinase (Erk)-inducible nitric oxide synthase (iNOS) signal pathways. Ang-1 expression, Tie2 phosphorylation, and nitric oxide (NO) release were increased at early shock. Exogenous Ang-1 maintained the vascular reactivity of SMAs after early hypoxia. Tie2-blocking antibody and the antagonists of Akt and eNOS antagonized Ang-1-induced maintenance in vascular reactivity and a slight release in NO at the early stage of shock. Ang-2 expression, Tie2 phosphorylation, and NO release were greatly increased at late shock, but exogenous Ang-2 further decreased the vascular reactivity of SMAs after late hypoxia. Tie2-blocking antibody and the antagonists of Erk and iNOS andtagonized the Ang-2-induced decrease in vascular reactivity and a large release of NO at the late stage of shock. Ang-1 and Ang-2 participated in the regulation of vascular reactivity after haemorrhagic shock. Ang-1 was mainly responsible for the hyperreactivity at early shock through the Tie2-Akt-eNOS pathway and an appropriate amount of NO release. Ang-2 was mainly responsible for the hyporeactivity at late shock through the Tie2-Erk-iNOS pathway and the release of a large amount of NO.