Influenza A(H1N1)pdm09 Virus Aggravates Pathology of Blood Vessels in Wistar Rats with Premorbid Acute Cardiomyopathy.

Influenza virus can infect the vascular endothelium and cause endothelial dysfunction. Persons at higher risk for severe influenza are patients with acute and chronic cardiovascular disorders; however, the mechanism of influenza-induced cardiovascular system alteration remains not fully understood. The aim of the study was to assess the functional activity of mesenteric blood vessels of Wistar rats with premorbid acute cardiomyopathy infected with Influenza A(H1N1)pdm09 virus. For this, we determined (1) the vasomotor activity of mesenteric blood vessels of Wistar rats using wire myography, (2) the level of expression of three endothelial factors: endothelial nitric oxide synthase (eNOS), plasminogen activator inhibitor-1 (PAI-1), and tissue plasminogen activator (tPA) in the endothelium of mesenteric blood vessels using immunohistochemistry, and (3) the concentration of PAI-1 and tPA in the blood plasma using ELISA. Acute cardiomyopathy in animals was induced by doxorubicin (DOX) following infection with rat-adapted Influenza A(H1N1)pdm09 virus. The functional activity of mesenteric blood vessels was analyzed at 24 and 96 h post infection (hpi). Thus, the maximal response of mesenteric arteries to both vasoconstrictor and vasodilator at 24 and 96 hpi was significantly decreased compared with control. Expression of eNOS in the mesenteric vascular endothelium was modulated at 24 and 96 hpi. PAI-1 expression increased 3.47-fold at 96 hpi, while the concentration of PAI-1 in the blood plasma increased 6.43-fold at 24 hpi compared with control. The tPA concentration in plasma was also modulated at 24 hpi and 96 hpi. The obtained data indicate that influenza A(H1N1)pdm09 virus aggravates the course of premorbid acute cardiomyopathy in Wistar rats, causing pronounced dysregulation of endothelial factor expression and vasomotor activity impairment of mesenteric arteries.

Intravenous Nicotinamide Riboside Administration Has a Cardioprotective Effect in Chronic Doxorubicin-Induced Cardiomyopathy.

Doxorubicin, which is widely used to treat a broad spectrum of malignancies, has pronounced dose-dependent side effects leading to chronic heart failure development. Nicotinamide riboside (NR) is one of the promising candidates for leveling the cardiotoxic effect. In the present work, we performed a comparative study of the cardioprotective and therapeutic actions of various intravenous NR administration modes in chronic doxorubicin-induced cardiomyopathy in Wistar rats. The study used 60 mature male SPF Wistar rats. The animals were randomized into four groups (a control group and three experimental groups) which determined the doxorubicin (intraperitoneally) and NR (intravenous) doses as well as the specific modes of NR administration (combined, preventive). We demonstrated the protective effect of NR on the cardiovascular system both with combined and preventive intravenous drug administration, which was reflected in a fibrous tissue formation decrease, reduced fractional-shortening decrease, and better antioxidant system performance. At the same time, it is important to note that the preventive administration of NR had a more significant protective effect on the animal organism as a whole. This was confirmed by better physical activity parameters and vascular bed conditions. Thus, the data obtained during the study can be used for further investigation into chronic doxorubicin-induced cardiomyopathy prevention and treatment approaches.

Influenza A Virus Causes Histopathological Changes and Impairment in Functional Activity of Blood Vessels in Different Vascular Beds.

It has been established that blood vessels are a target for influenza virus; however, the mechanism by which virus affects the cardiovascular system remains unknown. The aim of the study is the identification of histological changes and changes in the functional activity of the pulmonary and mesenteric blood vessels of Wistar rats. Wistar rats were intranasally infected with the influenza A(H1N1)pdm09 virus. At 24 and 96 h post infection (hpi), histopathological changes were observed in lung tissues with the absence of histological changes in mesenteric tissues. The functional activity of pulmonary and mesenteric arteries was determined using wire myography. In pulmonary arteries, there was a tendency towards an increase in integral response to the vasodilator and a decrease in the integral response to the vasoconstrictor at 24 hpi (compared with control). At 96 hpi, a tendency towards a decrease in the integral response to the vasoconstrictor persisted, while the response to acetylcholine was slightly increased. The functional activity of the mesenteric blood vessels was inverted: a significant decrease in the integral response to the vasodilator and an increase in the response to the vasoconstrictor at 24 hpi were observed; at 96 hpi, the integral response to the vasoconstrictor persisted, while the response to the vasodilator remained significantly reduced. Obtained data indicate the development of endothelial dysfunction in non-lethal and clinically non-severe experimental influenza virus infection.

Vascular region-specific changes in arterial tone in rats with type 2 diabetes mellitus: Opposite responses of mesenteric and femoral arteries to acetylcholine and 5-hydroxytryptamine.

AIMS: Type 2 diabetes mellitus (T2DM) ranks in the top 10 causes of mortality worldwide. The key factor of T2DM vascular complications is endothelial dysfunction. It is characterized by the vessels motor activity disruption and endothelium-derived factors imbalance. The blood vessels morphological and molecular heterogeneity greatly affects the changes occurring in T2DM. Therefore, we conducted a comparative study of vascular bed changes occurring in T2DM. MAIN METHODS: Male Wistar rats were fed a high-fat diet for 20 weeks, followed by a single streptozotocin injection (20 mg/kg). T2DM was confirmed with an oral glucose tolerance test. KEY FINDINGS: A dose-dependent contraction study showed an increase in third-order mesenteric arterioles response to serotonin but not to phenylephrine. These vessels also exhibited a decrease in acetylcholine-dependent relaxation and an increase in guanylate cyclase function. At the same time, the femoral arteries showed a tendency for increased acetylcholine-dependent relaxation. The blood plasma analysis revealed low bioavailable nitric oxide and high levels of endothelin-1 and ROS. SIGNIFICANCE: This knowledge, in conjunction with the features of the T2DM course, can allow further targeted approaches development for the prevention and treatment of vascular complications occurring in the disease.

Effects of three types of bariatric interventions on myocardial infarct size and vascular function in rats with type 2 diabetes mellitus.

AIMS: The effects of three types of bariatric interventions on myocardial infarct size were tested in the rat model of type 2 diabetes mellitus (T2DM). We also evaluated the effects of bariatric surgery on no-reflow phenomenon and vascular dysfunction caused by T2DM. MAIN METHODS: Rats with T2DM were assigned into groups: without surgery, sham-operated, ileal transposition, Roux-en-Y gastric bypass, and sleeve gastrectomy. Oral glucose tolerance, glucagon-like peptide-1, and insulin levels were measured. Six weeks after surgery, the animals were subjected to myocardial ischemia-reperfusion followed by histochemical determination of infarct size (IS), no-reflow zone, and blood stasis area size. Vascular dysfunction was characterized using wire myography. KEY FINDINGS: All bariatric surgery types caused significant reductions in animal body weight and resulted in T2DM compensation. All bariatric interventions partially normalized glucagon-like peptide-1 responses attenuated by T2DM. IS was significantly smaller in animals with T2DM. Bariatric surgery provided no additional IS limitation compared with T2DM alone. Bariatric surgeries reversed T2DM-induced enhanced contractile responses of the mesenteric artery to 5-hydroxytryptamine. Sleeve gastrectomy normalized decreased nitric oxide synthase contribution to the endothelium-dependent vasodilatation in T2DM. SIGNIFICANCE: T2DM resulted in a reduction of infarct size and no-reflow zone size. Bariatric surgery provided no additional infarct-limiting effect, but it normalized T2DM-induced augmented vascular contractility and reversed decreased contribution of nitric oxide to endothelium-dependent vasodilatation typical of T2DM. All taken together, we suggest that this type of surgery may have a beneficial effect on T2DM-induced cardiovascular diseases.

Albumin covering maintains endothelial function upon magnetic iron oxide nanoparticles intravenous injection in rats.

Magnetic iron oxide nanoparticles (IONP) present the promising instrument for broad-spectrum of clinical applications, for example, targeted drug delivery. Reactivity of nanoparticles depends on their surface area and material. In the blood plasma IONP are getting covered with an albumin crown, so it was decided to test this shell for biocompatibility. Male Wistar rats were anesthetized and underwent laparotomy. Abdominal aorta was connected to external hemodynamic loop with regulated blood flow. Hind body quarter got step-like blood flow changing from 30 to 150 mmHg and back. This was followed with i.v. injection of IONP, albumin solution or albumin-covered IONP and consequent similar flow changes. Central hemodynamics-heart rate and mean arterial pressure were registered throughout the experiment and no significant changes in these parameters were observed. Hind paw microcirculation level had the same dynamic in all groups under changing blood flow conditions. At the end, venous blood was collected for endothelin-1 and NO evaluation that showed similar changes and no endothelial damage. Mesenteric arteries and femoral artery reactivity were evaluated with wire myography. Mesenteric arteries had the most relaxing function preservation after albumin-covered IONP injection. Given data reveal advantage of albumin-coated IONP so this can be used for further investigations as a vascular-safe vehicle.

Biological Safety and Biodistribution of Chitosan Nanoparticles.

: The effect of unmodified chitosan nanoparticles with a size of ~100 nm and a weakly positive charge on blood coagulation, metabolic activity of cultured cardiomyocytes, general toxicity, biodistribution, and reactive changes in rat organs in response to their single intravenous administration at doses of 1, 2, and 4 mg/kg was studied. Chitosan nanoparticles (CNPs) have a small cytotoxic effect and have a weak antiplatelet and anticoagulant effect. Intravenous administration of CNPs does not cause significant hemodynamic changes, and 30 min after the CNPs administration, they mainly accumulate in the liver and lungs, without causing hemolysis and leukocytosis. The toxicity of chitosan nanoparticles was manifested in a dose-dependent short-term delay in weight gain with subsequent recovery, while in the 2-week observation period no signs of pain and distress were observed in rats. Granulomas found in the lungs and liver indicate slow biodegradation of chitosan nanoparticles. In general, the obtained results indicate a good tolerance of intravenous administration of an unmodified chitosan suspension in the studied dose range.

Nicotinamide riboside has protective effects in a rat model of mesenteric ischaemia-reperfusion.

Acute mesenteric ischaemia is a syndrome caused by inadequate blood flow through the mesenteric vessels, resulting in ischaemia and eventual gangrene of the bowel wall. Although relatively rare, it is a potentially life-threatening condition. The maintenance of haemodynamic stability, along with adequate oxygen saturation, and the correction of any electrolyte imbalance, are of the utmost importance. However, nicotinamide adenine dinucleotide (NAD) biosynthesis modulation by precursor introduction can also be a powerful tool for preventing injury. Nicotinamide riboside is a pyridine-nucleoside form of vitamin B3 that functions as a precursor to NAD+ . The present study investigated nicotinamide riboside's effect on endothelium functional state, microcirculation and intestinal morphology in acute mesenteric ischaemia and reperfusion. Mesenteric ischaemia was simulated after the adaptation period (15 minutes) by occluding the superior mesenteric artery for 60 minutes, followed by a reperfusion period of 30 minutes. The functional state of intestinal microcirculation was evaluated by laser Doppler flowmetry. Endothelial functional activity was studied by using wire myography. Intestinal samples were stained with haematoxylin and eosin for histological analysis. The results revealed that nicotinamide riboside protects the intestinal wall from ischaemia-reperfusion injury, as well as improving the relaxation function of mesenteric vessels. Nicotinamide riboside's protective effect in small intestine ischaemia-reperfusion can be used to reduce ischaemia-reperfusion injury, as well as to preserve intestinal grafts until transplant.