Relative Cardiac Mass Research Articles

Restoration of cardiac metabolic flexibility by glutathione in ecstasy-treated male Wistar rats is dependent of circulating testosterone and xanthine oxidase/uric acid/caspase 3 modulations

Introduction and objectives: The abuse of ecstasy as a recreational drug is widespread, despite its complications such as cardiac injury and dyslipidaemia. Till date, the involvement of testosterone and xanthine oxidase (XO)/ uric acid (UA)/ caspase 3 signaling in ecstasy-induced cardiac injury and dysmetabolism is yet to be reported. The possible effect of glutathione in ecstasy-induced cardiac injury is also yet to be documented. Hence, this study was designed to evaluate the involvement of circulating testosterone and XO/UA/caspase 3 pathway in ecstasy-induced cardiac injury and dysmetabolism. Also, the effect of glutathione in ecstasy-induced cardiac injury was explored. Methods: Forty eight male Wistar rats were randomly distributed into six groups (n= 8). The control rats received distilled water, glutathione-treated rats received 15 mg/kg of glutathione, low dose ecstasy-treated (LDE) and high dose ecstasy-treated (HDE) rats received 5 mg/kg and 15 mg/kg of ecstasy respectively, LDE + glutathione-treated rats received 15 mg/kg of glutathione and 5 mg/kg of ecstasy, and HDE + glutathione-treated rats received 15 mg/kg of glutathione and 15 mg/kg of ecstasy via gavage for 8 weeks. Results: Ecstasy significantly increased the relative cardiac mass, but did not significantly alter the body weight gain and absolute cardiac mass. It also caused increased mean arterial pressure, diastolic pressure, heart rate, PR interval, and QT interval. In addition, it led to insulin resistance and improved β-cell function, increased fasting levels of insulin and plasma and cardiac lactate, lactate dehydrogenase, creatinine kinase, troponin I and T, C-reactive protein, total cholesterol, triglycerides, LDL-C, lipid peroxidation, TNF-α, IL-1β, IL-6, and NF-kB levels. These alterations were accompanied by increased plasma and cardiac levels of XO, UA, and caspase 3, reduced circulating testosterone, glutathione content, and glucose-6- phosphate dehydrogenase, and distortion of cardiac histo-architecture. However, glutathione administration averted ecstasy-driven cardiac injury and metabolic derangement. Conclusions: Taken together, these findings infer that ecstasy induces defective cardiac metabolic flexibility, which is associated with upregulation of XO/UA/caspase 3 signaling and downregulation of circulating testosterone and glutathione defense mechanisms. Also, these results indicate that glutathione alleviates ecstasy-induced cardiac metabolic inflexibility by suppressing XO/UA/caspase 3 signaling and enhancing circulating testosterone and glutathione defense mechanisms. Self funded This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Effects of Clofibrate on Salt Loading‐Induced Hypertension in Rats

The effects of clofibrate on the hemodynamic and renal manifestations of increased saline intake were analyzed. Four groups of male Wistar rats were treated for five weeks: control, clofibrate (240 mg/kg/day), salt (2% via drinking water), and salt + clofibrate. Body weight, systolic blood pressure (SBP), and heart rate (HR) were recorded weekly. Finally, SBP, HR, and morphologic, metabolic, plasma, and renal variables were measured. Salt increased SBP, HR, urinary isoprostanes, NOx, ET, vasopressin and proteinuria and reduced plasma free T4 (FT4) and tissue FT4 and FT3 versus control rats. Clofibrate prevented the increase in SBP produced by salt administration, reduced the sodium balance, and further reduced plasma and tissue thyroid hormone levels. However, clofibrate did not modify the relative cardiac mass, NOx, urinary ET, and vasopressin of saline-loaded rats. In conclusion, chronic clofibrate administration prevented the blood pressure elevation of salt-loaded rats by decreasing sodium balance and reducing thyroid hormone levels.

Prenatal hypoxia induces increased cardiac contractility on a background of decreased capillary density

BackgroundChronic hypoxia in utero (CHU) is one of the most common insults to fetal development and may be associated with poor cardiac recovery from ischaemia-reperfusion injury, yet the effects on normal cardiac mechanical performance are poorly understood.MethodsPregnant female wistar rats were exposed to hypoxia (12% oxygen, balance nitrogen) for days 10–20 of pregnancy. Pups were born into normal room air and weaned normally. At 10 weeks of age, hearts were excised under anaesthesia and underwent retrograde 'Langendorff' perfusion. Mechanical performance was measured at constant filling pressure (100 cm H2O) with intraventricular balloon. Left ventricular free wall was dissected away and capillary density estimated following alkaline phosphatase staining. Expression of SERCA2a and Nitric Oxide Synthases (NOS) proteins were estimated by immunoblotting.ResultsCHU significantly increased body mass (P < 0.001) compared with age-matched control rats but was without effect on relative cardiac mass. For incremental increases in left ventricular balloon volume, diastolic pressure was preserved. However, systolic pressure was significantly greater following CHU for balloon volume = 50 μl (P < 0.01) and up to 200 μl (P < 0.05). For higher balloon volumes systolic pressure was not significantly different from control. Developed pressures were correspondingly increased relative to controls for balloon volumes up to 250 μl (P < 0.05). Left ventricular free wall capillary density was significantly decreased in both epicardium (18%; P < 0.05) and endocardium (11%; P < 0.05) despite preserved coronary flow. Western blot analysis revealed no change to the expression of SERCA2a or nNOS but immuno-detectable eNOS protein was significantly decreased (P < 0.001) in cardiac tissue following chronic hypoxia in utero.ConclusionThese data offer potential mechanisms for poor recovery following ischaemia, including decreased coronary flow reserve and impaired angiogenesis with subsequent detrimental effects of post-natal cardiac performance.

Myocardial and plasma renin-angiotensinogen dynamics during pressure-induced cardiac hypertrophy.

Plasma and left ventricular (LV) renin and angiotensinogen concentrations were assessed in a rat model of pressure-overload cardiac hypertrophy to determine if myocardial levels remained proportional to plasma levels over time. Three days after subdiaphragmatic aortic constriction (AC), LV hypertrophy was evident and renin concentrations in both plasma and LV, although not significantly elevated, were positively correlated with relative cardiac mass. After 42 days AC, LV hypertrophy remained, plasma and LV renin and angiotensinogen levels were not different from shams, and there was no correlation between renin and relative cardiac mass. Furthermore, LV renin and angiotensinogen concentrations remained at approximately 25 and 4%, respectively, of those in plasma throughout the experiment. Myocytes from 3-day AC and sham-treated rats contained little renin as did LV from 48-h anephric rats. Incubations using calculated concentrations of myocardial interstitial renin and angiotensinogen revealed significant angiotensin I generation. These data suggest that LV renin in this model varies directly with plasma renin, is confined to the interstitial space, and can generate significant intramyocardial angiotensin I.

Mesenteric Small Artery Changes After Vasoconstrictor Infusion in Young Rats

We evaluated whether chronic alpha 1-adrenergic stimulation, angiotensin II (AII), or increased blood pressure (BP) alters resistance arterial structure and function. Structural parameters and wall tension were recorded in mesenteric small arteries (MrA) isolated from 6-week-old normotensive Wistar Kyoto rats that had been infused for 4 days with saline (WKY), 2 mg/kg/day phenylephrine (WKY + PHE), or 0.3 mg/kg/day AII (WKY + AII) and from saline-infused spontaneously hypertensive rats (SHR). During the experimental period, systolic BP (SBP) did not change in WKY but increased in WKY + PHE, WKY + AII, and SHR. Relative cardiac mass did not differ between SHR and WKY, but was increased in WKY + PHE and WKY + AII. Stiffness and optimal lumen diameter of MrA did not differ between WKY and SHR and were not altered in WKY + PHE or WKY + AII. Maximal contractile responses and sensitivities for vasconstrictors and calcium in vessels of WKY + AII and SHR did not differ from those in WKY. In vessels of WKY + PHE, maximal responses to vasoconstrictors and sensitivities for norepinephrine (NE) and PHE were reduced. Relaxing responses to isoproterenol (ISO) and Na-nitroprusside did not differ between SHR and WKY and were not altered in WKY + PHE and WKY + AII. Those to acetylcholine (ACh) were reduced in WKY + PHE. Media cross-sectional area and media thickness were significantly larger in WKY + AII and SHR as compared with WKY but were not altered in WKY + PHE. These data indicate that in young rats AII leads to small artery hypertrophy and that neither increased BP or increased vasconstriction appear to be involved therein. Chronic alpha 1-adrenergic stimulation, on the other hand, did not modify small artery structure but resulted in nonselective reduction of arterial smooth muscle contractile reactivity.

Consequences of severe copper deficiency are independent of dietary carbohydrate in young pigs

The ability of carbohydrates (CHO), such as fructose and sucrose, to aggravate copper deficiency in rats and the recent dietary trends of Western human populations led to the suggestion that the Cu X CHO interaction may be pertinent to public health. This hypothesis was tested with pigs because their cardiovascular and gastrointestinal systems closely resemble those of humans. Weanling pigs were fed a diet containing either 59% sucrose or cornstarch with either deficient (0.8 mg/kg diet) or adequate (6.4 mg/kg) copper for 10 wk. Plasma and tissue copper, the activities of plasma ceruloplasmin ferroxidase and erythrocyte Cu,Zn-superoxide dismutase, hematocrits, and serum cholesterol and triglyceride were all decreased (p less than 0.05) and relative cardiac mass was increased (p less than 0.05) by severe dietary copper deficiency. The type of dietary CHO did not differentially influence the values of these variables. Thus, these data fail to support the hypothesis that the Cu X CHO interaction observed in rats represents a health risk for humans.

Consequences of copper deficiency are not differentially influenced by carbohydrate source in young pigs fed a dired skim milk-based diet

Carbohydrates (CHO) such as fructose (FR) or sucrose, but not starch (ST), aggravate the consequences of dietary copper (Cu) deficiency in rats. To evaluate whether this Cu X CHO interaction is pertinent to human health, the pig was used as an animal model. In two studies, 66 weanling pigs were fed dried skim milk (DSM)-based diets for 10 wk with 20% of the total calories provided as either FR, glucose, or ST and containing either deficient (1.0-1.3 micrograms/g diet) or adequate (7.1 micrograms/g) levels of Cu. Plasma and tissue levels of Cu, the activities of plasma ceruloplasmin ferroxidase and erythrocyte Cu, Zn-superoxide dismutase, and hematocrits were lower (p less than 0.05) in animals fed Cu-deficient diets. The relative cardiac mass of all Cu-deficient groups was greater (p less than 0.05) than that of animals fed Cu-adequate diets. These effects were in general unaffected by type of CHO. For comparison, weaned male rats were also fed DSM-based containing diets ST or FR with adequate or deficient Cu for as long as 10 wk. Rats consuming the Cu-deficient diets were characterized by significantly lower hematocrits, decreased tissue Cu levels, and enlarged hearts, regardless of the CHO source. Together, these data demonstrate that DSM-based diets are not suitable for delineation of potential Cu X CHO interactions, and one or more components of DSM may exacerbate the consequences of dietary Cu deficiency.