A variety of biological functions is attributed to the renin-angiotensin system (RAS). One of them is regulating vascular tone through its final effector Angiotensin II (Ang II). Ang II action is mediated by the Angiotensin type 1 receptor (AT1-R) which plays a role in vasoconstriction, and Angiotensin type 2 receptor (AT2-R) which may result in vascular relaxation through the releasing of endothelium mediates relaxation factors such as Nitric Oxide (NO). Therefore, this study investigated the role of AT2-R in vasodilation after blocking the effect of AT1-R in the rat aorta. Furthermore, it is to determine whether or not Ang II through NO has a role in rat aorta dilation via using valsartan. For control isolated aortic rings were preincubated with Valsartan (AT1- R inhibitor) and then stimulated with angiotensin II dose-dependent. For treating aortic rings different blockers and inhibitors were used. Pd123177 (AT2- R inhibitor) (20 μM), an inhibitor of PKA H-89 (10 μM), eNOS inhibitor L-NAME (0.3 mM), with group of K channel blockers such as TEA (1 mM), 4-AP (1 mM), BaCl2 (1 mM), clotrimazole (0.03 mM) and GLIB (0.01 mM). Our analysis demonstrates vasodilation in aortic rings induced by Ang II after blocking ATI-R and this response was highly reliant on PKA/eNOS and cyclic guanosine monophosphate (cGMP). The data from this investigation provided evidence that Ca2 + activated K+ channels (KCa) and Voltagedependent K channel (KV) mediated Ang II vasorelaxation. Finally, these results indicate that angiotensin II primarily induces dilatation AT2-R after inhibiting the angiotensin AT1 receptor through a cascade of signaling pathways involving many enzymes and plasma membrane protein channels.

Mercury accumulation affects the gastrointestinal, and renal systems. In this study, we aimed to study the physiological, and histological effects of mercury oxide on the liver and kidney in male Wistar rats. During 22 days, we divided 25 rats into 5 groups. The control group is placed first, followed by vinegar, low, medium, and high dose mercury groups. The control group was given only water. The vinegar-only group was given only vinegar. Mercury oxide-treated (HgO) group was given HgO 0.375 mg/kg/day. Mercury oxide treated group given HgO 1.5 mg/kg/day. Mercury oxide-treated (HgO) group was given HgO 4.5 mg/kg/day. We studied the levels of ALP, LDH, AST, ALT, albumin, creatinine, and urea. Histopathology of the liver and kidney were also studied. The result of this study was hepatic sinusoid dilation, renal tubule degeneration, and glomerulus shrinkage. This study showed non-significant differences among groups in terms of renal glomerulus diameter. The results showed that HgO at dose (1.5 mg/kg/day) had significantly higher levels of LDH, ALT, and AST enzymes when compared to the control group. While at the highest dose of mercury oxide (4.5 mg/kg/day), LDH, ALT, and AST enzyme levels decreased when compared to the lower doses. Our results showed a non-significant increase in urea level. Consequently, our investigation demonstrated that exposure to mercury oxide after therapy may result in toxicity to the kidneys and liver.

Type 2 Diabetes Mellitus is Among the most prevalent and globally widespread metabolic disorders. Though it has been associated with elderly people, recently the prevalence of younger individuals affected with T2DM has significantly increased. Currently, there is a broad range of diabetic biomarkers with those extensively used in clinical medicine such as HbA1c and those on ongoing research. Despite the competence of current diabetes biomarkers, they all display limitations in terms of accuracy and convenience, for this reason, there is a continuous urge to discover reliable, precise, and conventional biomarkers for early diagnosis and treatment of patients. This review encompasses a comprehensive background on both traditional as well as novel T2DM biomarkers therefore guides future research.

The study aimed to investigate the effects of arsenate (As) exposure on body weight, and kidney enzymes activities, assess histopathological changes in this tissue, and explore the potential protective role of spirulina (Sp) in reducing the harmful impacts of (As) on kidney health. The research utilized forty-eight female Wistar rats and divided them into six groups, including a control group that fed a normal diet and distilled water, the second group the rat treated with a 5mg/kg body weight of sodium arsenate-only group, the group three and four the rats treated with spirulina at different doses (300mg and 600mg), and the last group treated with combined (As) and (Sp) treatments. After four weeks of the experiment, the kidney was collected for enzyme analysis and histological examination. The results showed that As exposure decreased body weight (BW) compared to the control group, while (Sp) supplementation partially improved body weight. Arsenate exposure significantly increased the levels of aspartate aminotransferase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) enzymes in kidney tissues. However, spirulina supplementation at different doses reduced the enzyme levels, albeit statistically not significantly. The histological examination revealed As exposure resulted in necrosis, congestion, leukocyte infiltration, glomerular atrophy, and fibrosis, while Sp supplementation showed limited effects on reducing these changes. Overall, this study contributes to the understanding of the toxic effects of As and suggests that Sp supplementation may offer some protection against its harmful impacts …

Angiotensin II (Ang II), a mitogen-activated peptide, exerts numerous effects on the cardiovascular system including the regulation of blood pressure. The current study focused on the potential mechanisms that seem to be involved in Ang II vasodilation using bovine aortic endothelial cells (BAE-1) cell lines. Expression of the Ang II receptor (AT2) in BAE-1 was checked by western blots in the presence of valsartan (AT1 inhibitor). To check if Ang II’s vasodilator impact was mediated by the nitric oxide (NO) pathway, the Griess reagent was used. Furthermore, cell-attached patch-clamp and fire-polished borosilicate electrodes with a resistance of 3–5 MΩ in the working solutions was used to record membrane currents from treated BAE-1. BEA-1 revealed 50 kDa immunoreactive bands that matched AT2. The concentration of AT2 was elevated in valsartan-treated cells in comparison to control cells. The biochemical experimental data indicated that the NO level increased in a concentration-dependent manner. Meanwhile, Ang II at a concentration of 1 µM, the level of NO increased more than at 100 µM. In patch-clamp experiments, K current and chord conductance were enhanced after incubation of Ang II with valsartan. When 100 µM Ang II was added, the current peaked rapidly and after 15 min of incubation, the maximum value was obtained, as opposed to 10 min and control (110.9 ± 13.3 pA control, 141.4 ± 30.4 pA after 10 min and 174.4 ± 49.3 pA after 15 min). Ang II type two receptor inhibitor (PD1231777) reduced the current and conductance induced by Ang II. The presented data revealed that Ang II released NO via the activation of AT2. K currents were stimulated by Ang II and evoked mainly a current consistent with the activation of K channels.

URTICA DIOICA (UD) is used for a number of therapeutic purposes. Has traditionally been used in the control of cardiovascular disorders, especially hypertension. Also, the leaf extract of UD has been reported to improve glucose homeostasis in vivo. This raises the question of the relationship between UD, diabetes, and heart disorders. Therefore, this study aimed to evaluate the effect of watery leaf extract UD on the heart parameters associated with diabetes mellitus (DM) in Wistar rats. Animals were divided into 4 groups (N = 25). The untreated normal control rats only received distilled water (n = 8).), The diabetic control rats group received alloxan 120 mg/Kg body weight (n = 7), the diabetic rat group treated with UD at 250 mg/kg body weight (n = 5), and the diabetic rats that received UD extract at 500 mg/Kg body weight (n = 5) orally twice daily for 5-6 days. Data showed that in the diabetic group heart rate decreased and induced bradyarrhythmia. After treating diabetic rats with 250 mg/kg enhancement in heart rate was recorded. Additionally, increasing the UD concentration to 500mg/kg further increases the heart rate to the normal value. The current study indicates a widening in QRS, which seems to be disturbances of intraventricular conduction that can be seen in right and left bundle branch blocks, heart failure, and myocardial ischemia. Conclusively, these data show that UD appears to have antidiabetic and noncytotoxic properties, it is associated with reducing the effect of diabetics on the heart

Introduction: The rapid and recent rise in the pandemic of cardiovascular disease implies that the environment plays a significant role. Numerous biological systems, such as the cardiovascular, blood-forming organs, liver, and kidneys, can be affected by gasoline and smoking. Because filling station employees, repair service workers, gasoline truck drivers, and refinery workers are all at a greater risk of being exposed to gasoline fumes. Even though gasoline and smoking have been investigated for so many years, few studies have looked into the effects of gasoline exposure combined with smoking on a variety of physiological mechanisms. As a result, we propose that combining gasoline exposure with smoking is a risk factor for cardiovascular diseases and impaired hepatic function. Methods: The study included 95 male adult volunteers who worked with gasoline and were exposed to different fuel derivatives as study group and age and sex-matched seemingly healthy non-exposed people as the controls. Questionnaire interviews were used to collect socio-demographic data and a standard technique was used to collect the blood samples. The levels of cholesterol, HDL4, LDL-C, triglyceride, and VLDL were measured, as well as for liver enzymes ALP, AST, ALT, indirect bilirubin, direct bilirubin, and total bilirubin were measured. Results: Our data suggest that smoking with gasoline exposure causes an increase in total and bad cholesterol levels, as well as a significant shift concerning the control group in lipid profile and liver enzymes. the exposed group had higher levels of ALP, and AST and significantly increased. In the nonsmoker exposed group D-bilirubin decreased in comparison to the control and exposed smoker group. Conclusion: This research concluded that the liver enzymes (ALP, AST, ALT) were higher among workers who smoke and are exposed to gasoline than in control subjects, similarly, the bad cholesterol also increase. Therefore, people who smoke and are handled with gasoline are at a higher risk of having heart and hepatic diseases.

Various chemical mediators of inflammation such as serotonin, Bradykinin (BK), histamine, substance P, and ATP have been linked to the pathophysiology of multiple vascular ailments, including atherosclerosis, migraine, and myocardial infarction. Cardiovascular performance seems to be significantly regulated by BK. It is also becoming more and more recognized as a component of how medications that affect the liver, kidney, and circulation work. Tetraethylammonium (TEA), a nonselective potassium channel blocker, works as an antiarrhythmic drug in addition to inhibiting potassium channels to affect repolarization. We studied levels of heart electrical activity as well as the physiological effects of different dosages of BK and TEA administered intravenously on a cardiac arrhythmia caused by BaCl2 in vivo. After measuring the electrocardiographic (ECG) parameters in male Wistar rats, which were anesthetized and had electrodes implanted subcutaneously into the right forelimb and left hind limb, the ECG waves and parameters were recorded and analyzed using the LabChart software and the Bio Amp of ADInstruments data acquisition system. Barium Chloride, in doses of 10 and 20 mg/kg (i.v), produced intense and persistent bradycardia associated with prolonged QTc at was observed in the ECG in vivo recording, if not treated after 20-25 in rats were dying. Bradykinin and TEA also produced a similar pattern of a fall in heart rate but inhibited mortality. In addition, the responses produced by TEA are of greater magnitude as compared to the BK. In conclusion, Bk and TEA produce cardioprotective activity in rats.

Taurine, a ubiquitous endogenous sulfur-containing amino acid, possesses numerous pharmacological and physiological actions, including antioxidant activity, modulation of calcium homeostasis, and antiapoptotic effects. There is mounting evidence supporting the utility of taurine as a pharmacological agent against heart disease, including chronic heart failure. This study investigated the potential protective effects of taurine, on behavior and cardiovascular function in the male rat following arrhythmia induced by the social stressor. Here, we studied levels of heart electrical activity following experimental conditions: Cage control, social isolation in standard rat housing for 14 days, and pharmacokinetics effect of intravenous administration of different doses of taurine on arrhythmia induced by social isolation in vivo after. The ECG signals and parameters were recorded and analyzed with the aid of Bio Amp of ADInstruments data acquisition system and LabChart software. The results showed infusion of Taurine 1mg/kg/hr, 2.5mg/kg/hr and 10mg/kg/hr non significantly change heart rate (BPM), QRS intervals, S amplitude (mV), T amplitude (mV), ST height (mV), JT height (mV), QT intervals (s) and QTc (s).

Bradykinin (BK) plays a critical role in intervening relaxation in vascular smooth muscle through distinctive mechanisms. The current project is designed to study the role of PKA, calcium-dependent potassium (BKca, IKca,andSKca) channels, voltage-dependent potassium channel (Kv) and inward rectifier potassium channel (Kir) in BK interceded response and to determine functionally the mechanisms underlying BK mediated relaxation, utilizing standard tissue bath protocols. The results of the current work showed that BK inducing vasorelaxation is mediated by PKA which activate eNOS (endothelial nitric oxide synthase) followed by a subsequent release of nitric oxide (NO) from endothelial cells since the protein kinase inhibitor (H-89) significantly reduced Emax and pIC50. Similarly, in rings pre-incubated with L-NAME (3×10-4M) significantly inhibited vasorelaxation induced by BK. Furthermore, both Kca and Kv played an interesting role in vasorelaxation mediated by BK (1×10-6 to 3×10-3 M) in phenylephrine (PE) precontracted aortic rings, pre-incubated with tetraethylammonium (TEA) which reduced Emax with a slight reduction of pIC50 as compared to the control. Also, aortic rings pre-incubated with IK(Ca) blocker (clotrimazole) markedly reduced Emax but with a tendency of pIC50 elevation. In the present study, voltage-dependent potassium channels blocker (4-AP) significantly reduced the relaxant effects of BK and reduced Emax with altering pIC50 values significantly. On the other hand, BaCl2 tends to enhance the relaxation induced by BK and significantly elevated Emax. Collectively, our findings indicate that BK-induced relaxation is dependent on the activation of PKA to release NO from endothelium which through a cascade of a signaling pathway, in turn, activate both IK(Ca) and Kv in rat artic vascular tissue

Nitric oxide (NO) is produced from virtually all cell types composing the cardiovascular tissue and regulates vascular function through fine regulation of excitation–contraction coupling. Endogenous metabolites play a major role in coronary autoregulation. Therefore, the aim of the present study is to investigate the contribution of Glyceryl trinitrate (GTN) and Adenosine 5-triphosphate (ATP) mediated relaxation in rat aortic smooth muscle in intact and endothelium denuded endothelium rings precontracted with Phenylephrine (PE). The thoracic aorta was isolated, cut into rings, and mounted in organ-bath chambers and isometric tension was recorded using PowerLab Data Acquisition System (Model ML 870). The results showed that GTN as NO donor produced dose-dependent relaxation in intact aortic rings precontracted with PE (1 μM) that disinhibited in the presence of Glibenclamide (GLIB), while GLIB attenuate the response induced by ATP in intact aortic rings. L-nitroarginine methylester (L-NAME) an antagonist for nitric oxide synthases (NOS), not abolish the response induced by GTN (Emax 55.28% ± 0.18). Caffeine, ATP receptors antagonist, were partially inhibit the relaxation induced by ATP (vasodilation rate decreased by about 20.57 %). In endothelium denuded aortic rings, vasorelaxation induced by ATP were significantly attenuated , while GTN significantly increased relaxation by removing endothelium. These results suggested that (1) ATP-dependent potassium channel did not involve in GTN inducing vasorelaxation while KATP and A2B receptors have a role in ATP mediated vasorelation (2) ATP partially dependent on endothelium in contrast to NO donors that independent to endothelium.

Sodium Nitroprusside (SNP) and Adenosine (Ado) are potent drugs used in the treatment of cardiovascular diseases. Nitric oxid (NO) is produced from virtually all cell types composing the cardiovascular and regulates vascular function through fine regulation of excitation–contraction coupling. Adinosine endogenous metabolites play a major role in coronary autoregulation. Therefore, the aim of the present study was to investigate the contribution of NO and Ado mediated relaxation in rat aortic smooth muscle in intact and denuded endothelium rings precontracted with phenylepherine (PE). The thoracic aorta was isolated, cut into rings, and mounted in organ-bath chambers and isometric tension was recorded using powerLab Data Acquisition System (Model ML 870). According to the results of the current study, incubation of aortic rings with Glybenclamide (GLIB) decreased the relaxation response induced by Ado (the vasodilation value rate decrease from 41.07±6.7 control to 18.54±4.6) in intact aortic rings. Lnitroarginine methylester (L-NAME), not abolished the response induced by SNP, whereas Nifedipine significantly enhanced the response induced by SNP in a dose-dependent manner in intact endothelium rings. The relaxation to Ado in intact aortic rings was slightly decreased (6.88± 1.01), but not abolished completely after incubation with Caffeine (Ado receptors antagonist). On the other hand, removing endothelium did not attenuated the vasorelaxation induced by SNP and increased relaxation response. While, vasorelaxation of Ado in aortic rings were partially attenuated by removing endothelium. These results suggested that (1) ATP-dependent potassium channel (KATP) did not involve in SNP inducing vasorelaxation, while have a role in Ado mediated vasorelation. (2) Vasorelaxation effect of NO is endothelium independent, while, Ado relaxation effect is endothelium dependent.