Dexamethasone-induced Hypertensive Rats Research Articles

Purification, molecular docking and in vivo analyses of novel angiotensin-converting enzyme inhibitory peptides from protein hydrolysate of moth bean (Vigna aconitifolia (Jacq.) Màrechal) seeds

The moth bean is a high-protein food legume. Enzymatic hydrolysates of food proteins demostrate health benefits. Search for diet related food protein hydrolysates is therefore within the scope of functional foods. Present study asertains to produce, screen and identify natural ACE-I inhibitory peptides derived from moth bean seed protein hydrolysates. The extracted protein was hydrolysed using alcalase, chymotrypsin, flavourzyme, papain, pepsin and trypsin respectively. Alcalase achieved the greatest degree of hydrolysis and ACE inhibition. The highest ACE-I inhibitory activity was exhibited by the peptide with the lowest molecular weight i.e. <3 kDa (IC50 11.19 ± 0.15 μg/mL). This was further separated by FPLC, followed by mass spectrometry. Molecular docking analysis showed the peptides IAWDFR and ADLPGLK bind to active sites whereas DKPWWPK and AVIPNAPNLR to non-active sites of the ACE molecule. In vivo administration of MBP hydrolysate to dexamethasone-induced hypertensive rats reduced their systolic blood pressure (125 ± 0.76 mmHg) compared with positive control (155 ± 3.13 mmHg). Moth bean protein peptides exhibit functional nutraceutical properties with adequate antihypertensive activity.

Olive cake reduces blood pressure, oxidative stress, aortic endothelial dysfunction and vascular remodeling, in dexamethasone-induced hypertensive rats

BACKGROUND/AIM: Hypertension is a global public health problem and a leading cause of cardiovascular morbidity and mortality. In this paper, we study the effect of olive cake (OC) on blood pressure, endothelial dysfunction, redox status and vascular remodeling in dexamethasone-induced hypertensive (HT) rats. METHODS: HT rats were divided into two groups fed standard diet supplemented (HT-OC) or not (HT) with OC at 7.5% for 28 days. A control (C) was submitted to standard diet for the same experimental period. RESULTS: Systolic, diastolic and mean blood pressures were higher in the HT vs C and decreased in HT-OC vs HT. Aortic nitric oxide value was decreased in the HT vs the C and increased in HT-OC vs HT. Aortic lipid and protein oxidation products were higher in the HT than C and lower in the HT-OC vs HT. Aortic antioxidant enzymes activities were reduced in HT than control and increased in the HT-OC vs HT. The aortic wall thickness, medial cross-sectional area, media to lumen ratio and the number of VSMCs were higher in the HT and the OC has regressed vascular redemptions. CONCLUSION: In hypertensive rats, OC may alleviate blood pressure and arterial remodeling by suppressing oxidative stress, increasing antioxidant activity, improving endothelial function, preventing smooth muscle proliferation and thickening of the tunica media.

Protective effects of olive cake against heart and kidney injury in dexamethasone-induced hypertensive rats

Protective effects of olive cake against heart and kidney injury in dexamethasone-induced hypertensive rats

Quantified Piper sarmentosum Roxb. Leaves Aqueous Leaf Extract and Its Antihypertensive Effect in Dexamethasone-Induced Hypertensive Rats

The quality control of raw herbal materials is important to ensure the safety, efficacy, and reproducibility of herbal products. Herbal products with consistent efficacy should be standardized and quantified based on their bioactive phytochemical compounds. Piper sarmentosum Roxb. has been reported for its antihypertensive activity. However, its antihypertensive effect on dexamethasone-induced hypertension still lacks information. In this study, the quality of two batches of raw P. sarmentosum leaf materials was assessed for heavy metal and microbial contents, and their aqueous extracts were assayed for antioxidant activity. The aqueous extract of the second batch of P. sarmentosum leaves was the only extract that passed the heavy metal and microbial limits and had the highest antioxidant activity (50.00 ± 2.88%); therefore, this extract was used for subsequent studies. The extract was quantified for two phytochemical markers, rutin (0.09 ± 0.002%) and vitexin (0.23 ± 0.007%), using a validated ultrahigh performance liquid chromatography method. The quantified extract (500 mg/kg/day orally) was able to lower the systolic blood pressure, diastolic blood pressure, and mean arterial pressure of dexamethasone-induced hypertensive rats comparable to the positive control drug, captopril. In summary, the quantified aqueous extract of P. sarmentosum based on rutin and vitexin lowers the blood pressure of dexamethasone-induced hypertensive rats, but its underlying mechanism warrants further investigation.

The effects of sacubitril/valsartan and ramipril on the male fertility in hypertensive rats.

OBJECTIVE:Renin angiotensinogen system (RAS) inhibitors, ramipril and sacubitril/valsartan are frequently used in the treatment of cardiovascular diseases. Although they are known as contraindicated during pregnancy in hypertensive women, there is not any outcome of their safety in male fertility after exposure to ramipril or sacubitril/valsartan. In this study, we aimed to evaluate the effects of ramipril and sacubitril/valsartan to highlight their safety in the male fertility in normotensive and hypertensive rats.METHODS:Adult male normotensive and dexamethasone-induced hypertensive rats were treated with sacubitril/valsartan, ramipril and saline for 18 days. Arterial blood pressures were verified using carotid artery cannulation. Male fertility parameters, including the testis weights, histopathologic scoring of the testis, sperm count, sperm motility, morphology, and serum testosterone levels, were analyzed in treated and nontreated normotensive/hypertensive rats.RESULTS:Sacubitril/valsartan or ramipril treatments did not reveal a significant difference in sperm production, testicular morphology, and radioimmunoassay of serum testosterone levels compared to the control group. However, sperm motility was significantly reduced in rats under RAS inhibition.CONCLUSION:This finding was likely mediated by the identification of Ang receptors in the tails of rat sperm given that Ang receptors may play a role in the modulation of sperm motility. Identification of RAS-related proteins involved in sperm motility may help to explain their roles in motility. Our data provide general safety evidence for the male fertilization ability after paternal sacubitril/valsartan and ramipril exposure.

Blockade of the Neprilysin and Angiotensin Ameliorates Oxidative Stress in the Cardiovascular Target Tissues of Dexamethasone-induced Hypertensive Rats

Blockade of the Neprilysin and Angiotensin Ameliorates Oxidative Stress in the Cardiovascular Target Tissues of Dexamethasone-induced Hypertensive Rats

Angiotensin converting enzyme and neprilysin inhibition alter pain response in dexhamethasone-induced hypertensive rats.

We hypothesized that renin-angiotensin system and neprilysin (NEP) inhibition can modulate the nociceptive parameters on hypertensive rats. The aim of this study is to assess the preventive and therapeutic effects of ramipril and sacubitril on the pain hypersensitivities, and their interaction mechanisms with high blood pressure. Antinociceptive effects of ramipril and sacubitril were compared with those of diclofenac. Threshold of pain assesments were recorded before drugs administration. After a 18 days treatment, normotensive and dexamethasone-induced hypertensive rats were evaluated on thermal hyperalgesia and mechanical allodynia tests. Blood pressure of rats were verified by mean arterial pressure measurement. Hypertensive rats showed significantly high pain threshold on thermal plantar test compared to that of normotensives. Among hypertensive rats, pain hypersensitivity was lowest in diclofenac group, followed by sacubitril group, while ramipril caused increased thermal and mechanical hypersensitivities. We found that NEP inhibition may play a role in nociception in hypertensive rats. NEP inhibitors may be suitable choice for the management of hypertension and pain because of their therapeutic and preventive effects on nociception and arterial blood pressure.

Active-site directed peptide l-Phe-d-His-l-Leu inhibits angiotensin converting enzyme activity and dexamethasone-induced hypertension in rats

Hypertension is the fundamental cause of cardiovascular and cerebrovascular disorders. Several natural and synthetic peptides are being used as antihypertensive agents, which target angiotensin converting enzyme (ACE), the master regulator of angiotensin (Ang) II production. In this study, we have evaluated ACE-inhibitory potential of the tripeptide l-Phenylalanyl-d-Histidyl-l-Leucine (l-Phe-d-His-l-Leu) in vitro and its antihypertensive effect in rat model of dexamethasone-induced hypertension. l-Phe-d-His-l-Leu was custom-designed by changing the configuration of penultimate amino acid residue (histidine) from C-terminal of Ang I, the site at which ACE acts upon and generates Ang II. l-Phe-d-His-l-Leu effectively inhibited ACE activity in a dose-dependent and competitive manner with an IC50 of 53.32 ± 0.13 nmol/L. Both fluorescence spectra and circular dichroism data revealed the direct interaction between l-Phe-d-His-l-Leu and ACE. In addition, molecular docking studies revealed the strong interaction of l-Phe-d-His-l-Leu with the critical active site amino acid residues of ACE. Further, the administration of l-Phe-d-His-l-Leu resulted in decrease in blood pressure (142 ± 3 mmHg) compared to dexamethasone alone group (167 ± 2 mmHg). Besides, l-Phe-d-His-l-Leu decreased the levels of circulating Ang II, and reduced fibrosis in heart and kidney, as evidenced by decreases in collagen deposition. Thus, the strategy of incorporation of d-amino acids in ACE-inhibitory peptides could be valuable in the development of antihypertensive drugs.

The effect of celecoxib on blood pressure and plasma oxidant/antioxidant status in co-administration with glucocorticoid in rat.

There is limited information about the concomitant uses of selective COX-2 inhibitors with corticosteroids or with antihypertensive medications. The aim of this study was to investigate the effect of celecoxib on blood pressure and plasma oxidant/antioxidant status in glucocorticoid-induced hypertension and in co-administration with captopril. Male Wistar rats received dexamethasone (30 μg/kg/day, s.c.) for 14 days. The tested groups received dexamethasone and orally treated with celecoxib (10, 25 or 50 mg/kg) or captopril (10, 20 or 40 mg/kg) or celecoxib (50 mg/kg) + captopril from day 8 to 14. Heart rate, systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial pressure (MAP) were measured using tail-cuff method. Hydroperoxides concentration and ferric reducing antioxidant power (FRAP) value were determined in plasma samples. Dexamethasone significantly increased BP and plasma hydroperoxides level and decreased body weights. High dose of celecoxib resulted in a small but significant increase in SBP, DBP and MAP in normotensive rats however it did not alter BP markers in dexamethasone-induced hypertensive rats. Celecoxib reduced the hypotensive effect of all doses of captopril in dexamethasone-induced hypertensive rats however the SBP and MAP was preserved near to normal at low and middle doses of captopril but DBP was more than normal at low dose of captopril. Heart rate was not significantly altered by different treatments. High dose of celecoxib also increased plasma hydroperoxides concentration without effect on FRAP level. In conclusion, celecoxib did not change blood pressure in glucocorticoid-induced hypertensive rats but may blunt the hypotensive effect of low dose of captopril. Further studies are needed for detailed information addressing the effects of COX-2 inhibitors on blood pressure in concomitant uses with corticosteroids.

ANTIHYPERTENSION STUDY OF ANREDERA CORDIFOLIA (TEN). V. STEENIS EXTRACT AND ITS FRACTIONS IN RATS THROUGH DEXAMETHASONE INDUCTION AND NITRIC OXIDE RELEASE.

Objective: The aims of this study were to prove the antihypertensive effect of Anredera cordifolia (Madeira vine) in dexamethasone-induced hypertensive rat and to determine the release of nitric oxide (NO).Methods: The rat’s blood pressure was measured by CODA® tail-cuff blood pressure system. A hypertensive rat model was developed on day 7 after administration of dexamethasone injection 0.5 mg/kg body weight (bw). NO levels were measured by spectrophotometry at a wavelength of 546 nm after reacting the serum sample with Griess reagent.Results: Ethanol extract of Madeira vine (EEMV), ethyl acetate fraction (EF), and water fraction (WF) could reduce systolic blood pressure at day 14 with a diastolic blood pressure (DBP) reduction of 26.8, 34.1, and 40.5 mmHg, respectively. DBP began to decrease from day 8 in the EEMV group with a DBP reduction of 24.1 mmHg. In the HF, EF, and WF groups, decreasing in DBP occurred on day 14 which were 22.0, 24.5, and 35.4 mmHg, respectively. NO level in rat serum was increased significantly at 90 min after administration of EEMV 100 mg/kg bw and WF 40.73 mg/kg bw. Increasing in NO levels due to EF with a dose of 1.66 mg/kg bw was not significantly different to control group.Conclusion: Ethanol extract of A. cordifolia had the antihypertensive effect in dexamethasone-induced hypertensive rats, so does its WF and EF. The mechanism of ethanol extract of Madeira vine leaves and its WF most likely due to vasodilation effect through NO-pathway, whereas EF could have other mechanism(s) of action.

ANTIHYPERTENSION STUDY OF ANREDERA CORDIFOLIA (TEN). V. STEENIS EXTRACT AND ITS FRACTIONS IN RATS THROUGH DEXAMETHASONE INDUCTION AND NITRIC OXIDE RELEASE.

Objective: The aims of this study were to prove the antihypertensive effect of Anredera cordifolia (Madeira vine) in dexamethasone-induced hypertensive rat and to determine the release of nitric oxide (NO).Methods: The rat’s blood pressure was measured by CODA® tail-cuff blood pressure system. A hypertensive rat model was developed on day 7 after administration of dexamethasone injection 0.5 mg/kg body weight (bw). NO levels were measured by spectrophotometry at a wavelength of 546 nm after reacting the serum sample with Griess reagent.Results: Ethanol extract of Madeira vine (EEMV), ethyl acetate fraction (EF), and water fraction (WF) could reduce systolic blood pressure at day 14 with a diastolic blood pressure (DBP) reduction of 26.8, 34.1, and 40.5 mmHg, respectively. DBP began to decrease from day 8 in the EEMV group with a DBP reduction of 24.1 mmHg. In the HF, EF, and WF groups, decreasing in DBP occurred on day 14 which were 22.0, 24.5, and 35.4 mmHg, respectively. NO level in rat serum was increased significantly at 90 min after administration of EEMV 100 mg/kg bw and WF 40.73 mg/kg bw. Increasing in NO levels due to EF with a dose of 1.66 mg/kg bw was not significantly different to control group.Conclusion: Ethanol extract of A. cordifolia had the antihypertensive effect in dexamethasone-induced hypertensive rats, so does its WF and EF. The mechanism of ethanol extract of Madeira vine leaves and its WF most likely due to vasodilation effect through NO-pathway, whereas EF could have other mechanism(s) of action.

Portulaca oleracea seeds extract does not prevent dexamethasone-induced hypertension in rats

Introduction: Portulaca oleracea is used as a nutritional and medicinal plant. The aim of this study was to assess the effect of hydroalcoholic extract of P. oleracea seeds in dexamethasone -induced hypertension in rats.Methods: For induction of hypertension, dexamethasone (30 μg/kg/d, subcutaneously) was administered for 14 days. Animals received P. oleracea extract as a pretreatment at various doses of 100, 200 and 400 mg/kg/d orally from 4 days before dexamethasone administration and during the test period. Systolic blood pressure (SBP) and heart rate were measured using tail-cuff method. The weight of thymus gland was estimated as a marker of glucocorticoid activity.Results: Dexamethasone injection significantly increased SBP (P < 0.001) while decreased the body and thymus weights (P < 0.05 and P < 0.001, respectively). Oral administration of P. oleracea could not prevent rising in SBP and decreasing in thymus weight. It also increased heart rate in hypertensive rats at the dose of 400 mg/kg/d (P < 0.05).Conclusion: The results of this study revealed that hydroalcoholic extract of P. oleracea seeds aggregates hypertension in dexamethasone-induced hypertensive rats. Hence, it should be used with caution in hypertensive patients receiving glucocorticoids.

Piper Sarmentosum Reduces Blood Pressure in Dexamethasone-Induced Hypertensive Rats

Piper Sarmentosum Reduces Blood Pressure in Dexamethasone-Induced Hypertensive Rats

Antihypertensive effect of allicin in dexamethasone-induced hypertensive rats

BackgroundGlucocorticoid is among the most commonly prescribed medicine. Unfortunately, Excess glucocorticoid level leads hypertension in 80–90% patients. Garlic (Allium sativum) has been used since ancient times and even nowadays as a part of popular medicine for various ailments and physiological disorders. Hence this study was undertaken to investigate the antihypertensive activity of allicin in dexamethasone induced hypertension in wistar rats. MethodsThe animals were randomly divided into four groups comprising of six rats per group. Hypertension was induced by subcutaneous injection of dexamethasone (10μg/rat/day) in hypertensive rats. Two hypertensive group animals were treated with nicorandil (6mg/kg/day, po) and allicin (8mg/kg/day, po) respectively for 8 weeks. While systolic blood pressure (SBP) was measured by the tail-cuff method weekly up to 8 weeks. ResultsDexamethasone treatment resulted in significant increase in SBP while allicin treatment significantly decreases the SBP. Thus, this study confirmed that allicin treatment for 8 weeks partially reverse dexamethasone induced hypertension in rats. Allicin treatment also attenuated dexamethasone-induced anorexia and loss of total body weight. ConclusionThis result suggests antihypertensive effects of allicin in dexamethasone induced hypertension. However, further studies are needed to explore the detailed mechanism of antihypertensive effect of allicin.

Hypotensive Activity of Ethanolic Extracts of Morinda citrifolia L. Leaves and Fruit in Dexamethasone-Induced Hypertensive Rat.

The effect of ethanolic extract of Morinda citrifolia leaves and fruit on blood pressure in dexamethasone-induced hypertension rat was evaluated. Total phenolic content of Morinda citrifolia leaves ethanolic extract (MCLEE) and Morinda citrifolia leaves ethanolic extract (MCFEE) was 1.789 ± 0.116 and 1.677 ± 0.051 mg of gallic acid equivalents per gram sample, respectively. Rutin level in MCLEE was 0.92 ± 0.19%, and scopoletin level in MCFEE was 0.46 ± 0.05%. MCLEE, MCFEE, and its extract combination significantly decreased the blood pressure of hypertensive rats. The combination group showed highest hypotensive activity by lowering systolic blood pressure by 16.71 ± 3.95%, diastolic blood pressure by 21.49 ± 7.90%, and mean arterial blood pressure by 19.58% ± 6.35. All extract treatments have not been able to repair or inhibit renal damage caused by dexamethasone induction.

Antihypertensive and antioxidant effects of hydroalcoholic extract from the aerial parts of Kelussia odoratissima Mozaff. in dexamethasone-induced hypertensive rats.

Background:Kelussia odoratissima Mozaff. is a monotypic endemic plant of Apiaceae growing wild in Iran. The aerial parts of this plant are used for treatment of hypertension, ulcer, and inflammatory conditions in folk medicine. In this study, the effects of hydroalcoholic extract of the aerial parts of K. odoratissima were evaluated in dexamethasone (Dex)-induced hypertension in male Wistar rats.Materials and Methods:For induction of hypertension, Dex (30 μg/kg/day) was administered subcutaneously for 14 days. In a prevention study, rats received oral K. odoratissima extract (100, 200, and 400 mg/kg) from 4 days before Dex administration and during the test period (days 1–18). In a reversal study, K. odoratissima extract was administered orally from day 8 to 14. Systolic blood pressure (SBP) was evaluated using tail-cuff method. The hydrogen peroxide (H2O2) concentration and ferric-reducing antioxidant power (FRAP) were measured in plasma samples.Results:Administrations of Dex significantly induced an increase in SBP and in plasma H2O2 and a decrease in body and thymus weights, and in FRAP value (P < 0.001). K. odoratissima extract dose-dependently prevented and reversed hypertension (P < 0.001). It also prevented and reduced the plasma H2O2 concentration and prevented the body weight loss upon Dex administration at all doses (100–400 mg/kg, P < 0.001) but failed to improve FRAP value.Conclusions:These results suggest antihypertensive and antioxidant effects of K. odoratissima extract in Dex-induced hypertension. Further studies are needed to elucidate the exact mechanism of the antihypertensive effect of this herbal medicine.

The effect of hydroalcoholic extract from the leaves of Moringa peregrina (Forssk.) Fiori. on blood pressure and oxidative status in dexamethasone-induced hypertensive rats.

Background:Moringa peregrina (Forssk.) Fiori. is a tropical tree growing in southeast of Iran. All parts of this plant have nutritional uses and pharmacological activities. The present study was designed to evaluate the effect of hydroalcoholic extract from the leaves of M. peregrina in dexamethasone (Dex)-induced hypertension in rats.Materials and Methods:Male Wistar rats received Dex (30 μg/kg, subcutaneously; s.c.) or saline (as vehicle, 1 ml/kg, s.c.) for 14 days. In a prevention study, the rats received M. peregrina extract (100, 200 and 400 mg/kg, orally) for 4 days, followed by Dex for 14 days. In a reversal study, the animals received M. peregrina extract orally from day 8 to 14. The systolic blood pressure (SBP) was measured using tail-cuff method. The hydrogen peroxide (H2O2) concentration and ferric reducing antioxidant power (FRAP) were assessed in plasma samples.Results:Dex significantly increased the SBP and the plasma H2O2 and decreased the plasma FRAP value (P < 0.001). M. peregrina extract at a dose of 400 mg/kg prevented (P < 0.01) but did not reverse Dex-induced hypertension in rats. It also dose-dependently reduced the plasma H2O2 concentration and improved the FRAP value upon Dex administration.Conclusions:The findings of the present study indicated the antioxidant and partially antihypertensive effects of the hydroalcoholic extract from the leaves of M. peregrina in Dex-induced hypertension. Further experiments on other fractions of the leaves and also other parts of this plant are suggested for better evaluation of its antihypertensive effect and finding its mechanisms of action.

Hydrogen sulfide is involved in dexamethasone-induced hypertension in rat

Glucocorticoid (GC)-induced hypertension is a common clinical problem still poorly understood.The presence of GC receptor (GR) in vascular smooth muscle and endothelial cells suggests a direct role for GC in vasculature. In response to hemodynamic shear stress, endothelium tonically releases nitric oxide (NO), endothelial-derived hyperpolarizing factor (EDHF) and prostacyclin contributing to vascular homeostasis. Recently, hydrogen sulfide (H2S) has been proposed as a candidate for EDHF. H2S is endogenously mainly formed from L-cysteine by the action of cystathionine-β-synthase (CBS) and cystathionine-γ-lyase (CSE). It plays many physiological roles and contributes to cardiovascular function. Here we have evaluated the role played by H2S in mesenteric arterial bed and in carotid artery harvested from rats treated with vehicle or dexamethasone (DEX; 1.5 mg/kg/day) for 8 days. During treatments systolic blood pressure was significantly increased in conscious rats. EDHF contribution was evaluated in ex-vivo by performing a concentration–response curve induced by acetylcholine (Ach) in presence of a combination of indomethacin and L-NG-Nitroarginine methyl ester in both vascular districts. EDHF-mediated relaxation was significantly reduced in DEX-treated group in both mesenteric bed and carotid artery. EDHF-mediated relaxation was abolished by pre-treatment with both apamin and charybdotoxin, inhibitors of small and big calcium-dependent potassium channels respectively, or with propargylglycine, inhibitor of CSE.Western blot analysis revealed a marked reduction in CBS and CSE expression as well as H2S production in homogenates of mesenteric arterial bed and carotid artery from DEX-treated rats. In parallel, H2S plasma levels were significantly reduced in DEX group compared with vehicle.In conclusion, an impairment in EDHF/H2S signaling occurs in earlier state of GC-induced hypertension in rats suggesting that counteracting this dysfunction may be beneficial to manage DEX-associated increase in blood pressure.

Antioxidant Effects of Bovine Lactoferrin on Dexamethasone-Induced Hypertension in Rat

Dexamethasone- (Dex-) induced hypertension is associated with enhanced oxidative stress. Lactoferrin (LF) is an iron-binding glycoprotein with antihypertensive properties. In this study, we investigated the effect of chronic administration of LF on oxidative stress and hypertension upon Dex administration. Male Wistar rats were treated by Dex (30 μg/kg/day subcutaneously) or saline for 14 days. Oral bovine LF (30, 100, 300 mg/kg) was given from day 8 to 14 in a reversal study. In a prevention study, rats received 4 days of LF treatment followed by Dex and continued during the test period. Systolic blood pressure (SBP) was measured using tail-cuff method. Thymus weight was used as a marker of glucocorticoid activity. Plasma hydrogen peroxide (H2O2) concentration and ferric reducing antioxidant power (FRAP) value were determined. Dexamethasone significantly increased SBP and plasma H2O2 level and decreased thymus and body weights. LF lowered (P < 0.01) and dose dependently prevented (P < 0.001) Dex-induced hypertension. LF prevented body weight loss and significantly reduced the elevated plasma H2O2 and increased FRAP values. Chronic administration of LF strongly reduced the blood pressure and production of ROS and improved antioxidant capacity in Dex-induced hypertension, suggesting the role of inhibition of oxidative stress as another mechanism of antihypertensive action of LF.

Neuronal Fos-like immunoreactivity associated with dexamethasone-induced hypertension in rats and effects of glucagon-like peptide-2

AimsDexamethasone-induced hypertension models have been used to study the mechanisms of glucocorticoid-induced hypertension, but the role of glucocorticoids in central cardiovascular regulation is not clearly understood. In the present study, we investigated the sites associated with dexamethasone-induced hypertension in the central nervous system in rats. We further investigated whether glucagon-like peptide-2 (GLP-2) was effective for dexamethasone-induced hypertension. Main methodsMale Sprague–Dawley rats were treated with saline or dexamethasone (0.03mg/kg/day, s.c) for 10days. GLP-2 (60μg/kg, i.v.) was given to rats after dexamethasone treatment. We measured systolic blood pressure by a tail-cuff method in conscious rats, and arterial blood pressure in anesthetized rats. Immunohistochemical techniques were used to detection of the c-fos protein (Fos). Key findingsFos-immunoreactivity (Fos-IR) in the dorsomedial hypothalamic nucleus (DMH) was higher in dexamethasone-treated rats than in saline-treated rats. However, Fos-IR in the infralimbic cortex, amygdala, and hippocampus was similar in saline-treated and dexamethasone-treated rats. Peripheral administration of GLP-2 reduced mean arterial blood pressure by 26%. After the peripheral administration of GLP-2, Fos-IR in the caudal ventrolateral medulla (CVLM) increased in dexamethasone-treated rats. SignificanceChronic dexamethasone treatment induced Fos-IR in the DMH. Peripheral administration of GLP-2 suppressed dexamethasone-induced hypertension in rats by enhancing inhibitory neuronal activity.