Systolic Blood Pressure In Animals Research Articles

1-trifluoromethoxyphenyl-3(1-propionylpiperidin-4-yl) urea (TPPU), a soluble epoxide hydrolase inhibitor attenuates high fat diet-induced cardiovascular and metabolic disorders in rats.

Obesity was induced in rats by feeding on a high fat diet (HFD), 60% w/w cholesterol, 20% w/w carbohydrates, and 20% w/w proteins for two months. Animals were fed on a HFD and treated concurrently with a single daily dose of vehicle or TPPU (2 mg/kg p.o) for two months. Body weights, blood pressure, and biochemical investigations of all animals were registered at 0, 1, and 2 months of the experimental period. Vehicle-treated rats fed on a HFD had a considerable increase in body weight compared to age-matched control animals fed on a regular diet (regular diet; 311.40 ±9.60 vs. HFD; 446 ± 12.67). The body weight of rats fed on a HFD and concurrently treated with 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4yl) urea (TPPU; 2 mg/kg p.o) daily for two months was significantly decreased (p<0.01). A significant (p<0.01) increase in the systolic blood pressure of animals and vascular dysfunction with blunted relaxant response to acetylcholine and sodium nitroprusside was evident in vehicle-treated animals fed on a HFD compared to control rats fed on a regular diet. These HFD-induced disorders were markedly attenuated in animals fed on a HFD and treated concurrently with a single daily dose of TPPU (2 mg/kg p.o). HFD diet-induced deleterious metabolic changes were prevented with concurrent administration of TPPU (2 mg/kg p.o). TPPU treatment decreased the HDF-induced increase in plasma creatinine levels (p<0.001) in rats. The adiponectin levels were decreased (p<0.001) in vehicle-treated rats fed on HFD for two months compared to control rats fed on a normal diet (p<0.001). Adiponectin levels were significantly (p<0.001) increased in rats fed on HFD and treated concurrently with TPPU (2 mg/kg p.o). HFD diet caused a marked increase in plasma leptin levels of animals which were significantly decreased in animals fed on a HFD and treated concurrently with TPPU for two months. Obese animals exhibited increased levels of plasma insulin compared to control animals fed on a regular diet which were significantly suppressed (p<0.001) by TPPU treatment. In the current investigation, TPPU treatment had a favorable impact on the levels of other metabolic parameters such as plasma cholesterol, triglycerides (TGs), low density lipoproteins (LDLs), and high density lipoproteins (HDL). HFD caused a profound increase in the serum liver enzymes, the effect was reversed by treatment of animals with TPPU (2 mg/kg p.o). The findings of our current study indicate the promising therapeutic potential of TPPU as a new drug candidate to manage obesity-induced cardiovascular and metabolic disorders. Soluble epoxide hydrolase inhibitors such as TPPU could prevent HFD-induced obesity and related cardiovascular and metabolic complications.

Effect of Grape Juice Consumption and Red Wine in the Osteoprotegerin Level and Systolic Blood Pressure in Rats Wistar Fed High - Fat Diet

High-fat diet contributes to reduction of bone mineral density and development of cardiovascular diseases. High-fat diet promotes the release substrate for formation of atheromatous plaques as well as increase production of cytokines and prostaglandins, interfering negatively in the concentration of osteoprotegerin - responsible for inhibiting the osteoclastogenesis. The interest by functional foods and their effects on diseases prevention is growing. This study evaluated the effect of whole grape juice consumption and red wine in the osteoprotegerin level and blood pressure in rats fed fat diet. They were used 40 rats Wistar Albino, adult, divided in groups: control - balanced diet; hiperlipydic – high-fat diet; wine - red wine + high-fat diet; juice - grape juice + high-fat diet. Water and ration were offered <i>ad libitum</i> and grape juice and red wine daily, during 60 days. Blood pressure was measured by a tail plestimograph and interleukin 6 (IL-6) and osteoprotegerin by ELISA. Results are expressed as mean and standard deviation. For comparison it was used ANOVA and Tukey as post-test, considering p<0.05. Systolic blood pressure (mmHg) was lower in grape juice group than hiperlipydic and red wine groups and similar to control group. IL-6 level (pg/mL) was lower in grape juice group than wine group, but it was similar to control and hiperlipydic groups. Hiperlipydic and wine groups showed lower osteoprotegerin level (pg/mL) than control and juice groups. Daily consumption of grape juice seems minimize the effects of high-fat diet in cardiovascular diseases risk and bone demineralization, by maintaining adequate concentration of osteoprotegerin and the systolic blood pressure in animals.

Effects of lisinopril on oxidative stress in brain tissues of rats with L-NAME induced hypertension

Objective: Arterial hypertension is often associated with pathologies related with oxidative stress. Angiotensin converting enzyme (ACE) inhibitors have been used as a safe and effective treatment of hypertension and coronary heart disease. However, the significance of ACE inhibitor usage in hypertension-induced cerebrovascular and neurodegenerative diseases is still unknown. In this study, we aimed to investigate the effects of lisinopril, an ACE inhibitor, on oxidative stress and antioxidant enzyme activities in brain tissues of rats with L-NAME (Nω-Nitro-L-Arginine Methyl Ester hydrochloride) induced hypertension. Methods: Thirty-two Sprague-Dawley rats were divided into four groups: Control, L-NAME, L-NAME plus lisinopril, and only lisinopril. Hypertension was induced by oral administration of the L-NAME (75 mg/kg/day) in drinking water for 6 weeks. Rats were treated with Lisinopril (10 mg/kg/day) for six weeks. Systolic blood pressures were measured at the first, third and sixth weeks by using tail cuff method. Malondialdehyde (MDA), Superoxide dismutase (SOD), Catalase (CAT) and Glutathione peroxidase (GSH-Px) activity were measured from the brain tissue. Nitric oxide (NO) levels were measured from plasma. Results: Our results showed that L-NAME leads to an increase in systolic blood pressure of animals. The antihypertensive effect of lisinopril was observed. MDA level was significantly increased, and antioxidant enzymes activities were decreased in L-NAME given group (p 0.05). Conclusion: In our study, hypertension led to oxidative damage in brain tissues. Although lisinopril prevents the hypertension induced oxidative damage, direct antioxidant effect was not observed. Further studies are needed in order to gain certainty effect of lisinopril in brain tissue.

Changes in Biomarkers of SH Rats Fed Novel and Traditional Sources of Vegetables

Purslane, sweet potato greens and collard greens have been known to decrease the complications of hypertension due to their high antioxidant capacity. The purpose of this study was to determine if the consumption of these greens decreased blood pressure, weight, and injury to the glomeruli of the kidney. Five week old Spontaneously Hypertensive (SHR) rats (n=44) were separated equally into four diet groups: control (AIN‐76A diet), purslane, sweet potato greens, and collard greens each added at 4%. SHR were fed their respective diets for six weeks. Blood pressure measurements and weight were recorded weekly and twice per week, respectively.Animals were euthanized and the kidneys were removed and placed in 10 % formalin. Tissues were fixed on two slides; stained with hematoxylin and eosin stain (H&amp;E) and the other stained with Periodic acid‐Schiff (PASH).Minimal variation in food intake was observed among the treatment groups, however, a significant reduction (P &lt; 0.05) in systolic blood pressure in animals fed purslane and sweet potato greens were observed. Preliminary results in kidney glomeruli are inconclusive.The results from these studies indicate that these novel and traditional vegetables show significant promise in significantly reducing risk factors associated with heart disease and other inflammatory chronic diseases.Grant Funding Source: USDA/AFRI

Long-term l-NAME treatment potentiates the blood–brain barrier disruption during pentylenetetrazole-induced seizures in rats

We investigated whether the severity of blood–brain barrier disruption caused by pentylenetetrazole-induced seizures is modified by long-term nitric oxide synthase inhibition in rats. Rats were given N-omega-nitro- l-arginine methyl ester ( l-NAME), a nitric oxide synthase inhibitor, in drinking water for 4 weeks, and then treated with pentylenetetrazole to induce seizures. Damage to the blood–brain barrier was investigated using Evans blue dye extravasation. Serum nitric oxide concentration was decreased in l-NAME-treated rats ( P < 0.01). l-NAME and/or pentylenetetrazole treatments elevated systolic blood pressure of animals ( P < 0.01). l-NAME caused an increase in the mortality rate after pentylenetetrazole injection leading to the death of animals at about 15 min after the onset of the seizure. Pentylenetetrazole-induced seizures in rats treated with l-NAME caused a significant increase in Evans blue dye extravasation into cerebral cortex, diencephalon and cerebellum, as compared with seizures evoked by pentylenetetrazole injection to l-NAME-untreated rats ( P < 0.01). Data presented here suggest that the degree of blood–brain barrier disruption induced by seizures is more pronounced in long-term nitric oxide deficiency.

Alterations in Aldosterone and Angiotensin II Levels in Salt-Induced Hypertension

Several studies have demonstrated that plasma renin-angiotensin activity is reduced in rats administered a high salt diet. We evaluated changes in plasma and tissue levels of aldosterone (ALDO) and angiotensin II (A-II), as well as the reduced-to-oxidized glutathione ratio. Male Dahl salt-sensitive (SS) rats were placed on either a high-salt (8% NaCl; HS) or a normal-salt (0.3% NaCl; NS) diet for 3 weeks. Prior to and weekly on the diets, systolic blood pressure was measured by tail cuff plethysmography. Levels of A-II and ALDO in plasma, heart, and kidney were analyzed by enzyme immunoassay. Reduced and oxidized gluthatione were simultaneously measured by HPLC fluorescence detection. Heart and kidney tissues were prepared for histological analysis. Systolic blood pressure in animals on a HS diet was significantly elevated above that of those on a NS diet. High salt caused a reduction in both plasma A-II and ALDO levels; while their levels in the heart and kidney were increased. Exposure to a high-salt diet led to the enlargement of both heart and kidney. The reduced-to-oxidized glutathione ratio in plasma, heart and kidney was lowered by exposure to a HS diet. Kidneys from animals on a high-salt diet showed fibroid necrosis associated with wrinkling and thickening of the glomerular capillary wall, while hearts were hypertrophic. Taken together, high dietary salt induces inappropriate activation of the local renin-angiotensin-aldosterone systems. Tissue levels of angiotensin II and aldosterone may be more reflective of the severity of vascular maladaptations than are plasma levels, and may play a greater role in the maintenance of hypertension.

Effect of Relaxin in Two Models of Renal Mass Reduction

Background: Relaxin (Rlx), a 6-kD protein hormone, belongs to the insulin growth factor family. We have previously shown that Rlx reduces interstitial fibrosis in a model of chronic papillary necrosis. Hypothesis: The purpose of this study was to extend these observations to a model of renal injury induced by mass reduction. Material and Methods: Renal mass was reduced by either infarction or surgical excision of both poles, with removal of the contralateral kidney. Two weeks later, creatinine clearance was done and animals from both groups implanted with osmotic pumps delivering either Rlx (2 µg/h) or vehicle (Veh). Treatment was continued for 4 weeks. The severity of the glomerular injury was quantified by planimetric measurements. Renal function was assessed by creatinine clearance and plasma creatinine. Results: Rlx significantly decreased systolic blood pressure in animals with infarction. This was accompanied by a decrease in serum creatinine and a slight improvement in creatinine clearance. The severity of the glomerular lesion was reduced by Rlx (sclerosis index, Veh 1.16 ± 0.13 vs. Rlx 0.74 ± 0.16, p = 0.037). In the excision group the animals were normotensive. In this group, Rlx treatment was accompanied by a decrease in serum creatinine (Veh 1.01 ± 0.03 vs. Rlx 0.81 ± 0.05 mg/dl, p = 0.02) and an increase in GFR (Veh 0.90 ± 0.14 vs. Rlx 1.33 ± 0.11 ml/min, p = 0.03). The sclerosis index was also reduced. Conclusion: Rlx decreases renal injury by at least two mechanisms, one by lowering blood pressure as seen in the infarction model, the other independent of blood pressure as seen in the normotensive excision model where there was also a significant functional improvement.

Decrease of myocardial infarct size with desferrioxamine: possible role of oxygen free radicals in its ameliorative effect.

The ability of an iron chelator, desferrioxamine, to inhibit the infarct size in in vivo rat heart was assessed. Anaesthetised rats were subjected to coronary artery ligation (CAL) for 72 hr and infarct size was measured macroscopically using TTC staining. Systolic blood pressure and ECG were monitored. Desferrioxamine (10 mg/kg and 20 mg/kg i.v.) administered half an hour after CAL markedly reduced the infarct size. However, drug treatment did not alter the systolic blood pressure of animals. In addition, desferrioxamine in vitro and in vivo demonstrated an inhibition of rat PMN-evoked and luminol-enhanced chemiluminescence. The capacity of desferrioxamine to impair the generation or to scavenge directly oxygen free radicals may be responsible for its beneficial effect on myocardial infarct size in rats.

Parathyroids, thyroid and development of hypertension in SHR.

Parathyroid glands play a significant role in the development of hypertension in spontaneously hypertensive rat (SHR), like in deoxycorticosterone acetate (DOCA) + NaCl model. Parathyroidectomy (PTX) performed after weaning delayed systolic blood pressure (SBP) increase and slowed heart rate (HR) in SHR for 42 weeks. These changes could not be attributed to decrease of serum calcium in PTX animals since supplementation of calcium, rendering serum calcium normal, did not reestablish SBP and HR to those of sham SHR. Moreover, in the thyroparathyroidectomized (TPTX) animals SBP and HR were increased by autotransplantation of parathyroids. When hypertension was established (week 15), PTX produced no more changes on cardiovascular parameters measured. These data clearly indicate that independent of thyroidectomy, PTX leads to a lesser degree of hypertension in young SHR, but was without effect on established hypertension. In conclusion, parathyroid glands are required for total development of the hypertensive process in SHR.