Plasma concentrations of endothelin-1 in spontaneously hypertensive rats and DOCA-salt hypertensive rats

To investigate the possible involvement of endothelin-1 (ET-1), an endothelium-derived potent vasoconstrictor peptide, in the pathophysiology of hypertension, plasma ET-1 levels in 15-week-old spontaneously hypertensive rats (SHR) and DOCA-salt hypertensive rats were measured with a sandwich-type enzyme immunoassay. The vasocontractile effect of ET-1 in aortic helical preparations was significantly more sensitive in DOCA-salt hypertensive rats than in control sham-operated rats, but plasma levels of ET-1 did not differ between them. Plasma ET-1 levels in genetically hypertensive rats (SHR and stroke-prone SHR) were significantly lower than those in age-matched normotensive Wistar-Kyoto (WKY) rats. The plasma concentrations of big ET-1, a precursor of ET-1, in both SHR and SHR-SP were significantly lower than those of WKY, suggesting that the production of ET-1 is decreased in rats of genetic hypertension. Although the vascular reactivity to ET-1 increased in both DOCA-salt hypertensive and genetically hypertensive rats, present findings of the plasma ET-1 levels suggest that the role of ET-1 in the vascular control system may be different in DOCA-salt hypertensive rats and genetically hypertensive rats.     

l-Arginine attenuates cardiovascular impairment in DOCA-salt hypertensive rats

Nitric oxide (NO) is essential for normal function of the cardiovascular system. This study has determined whether chronic administration of l-arginine, the biological precursor of NO, attenuates the development of structural and functional changes in hearts and blood vessels of deoxycorticosterone acetate (DOCA)-salt hypertensive rats. Uninephrectomized rats treated with DOCA (25 mg every 4th day sc) and 1% NaCl in the drinking water for 4 wk were treated with l-arginine (5% in food, 3.4 +/- 0.3 g x kg body wt(-1) x day(-1)). Changes in cardiovascular structure and function were determined by echocardiography, microelectrode studies, histology, and studies in isolated hearts and thoracic aortic rings. DOCA-salt hypertensive rats developed hypertension, left ventricular hypertrophy with increased left ventricular wall thickness and decreased ventricular internal diameter, increased inflammatory cell infiltration, increased ventricular interstitial and perivascular collagen deposition, increased passive diastolic stiffness, prolonged action potential duration, increased oxidative stress, and inability to increase purine efflux in response to an increased workload. l-Arginine markedly attenuated or prevented these changes and also normalized the reduced efficacy of norepinephrine and acetylcholine in isolated thoracic aortic rings of DOCA-salt hypertensive rats. This study suggests that a functional NO deficit in blood vessels and heart due to decreased NO synthase activity or increased release of reactive oxygen species such as superoxide may be a key change initiating many aspects of the cardiovascular impairment observed in DOCA-salt hypertensive rats. These changes can be prevented or attenuated by administration of l-arginine.     

Uridine adenosine tetraphosphate-induced contraction is increased in renal but not pulmonary arteries from DOCA-salt hypertensive rats

Uridine adenosine tetraphosphate (Up(4)A) was reported as a novel endothelium-derived contracting factor. Up(4)A contains both purine and pyrimidine moieties, which activate purinergic (P2)X and P2Y receptors. However, alterations in the vasoconstrictor responses to Up(4)A in hypertensive states remain unclear. The present study examined the effects of Up(4)A on contraction of isolated renal arteries (RA) and pulmonary arteries (PA) from DOCA-salt rats using isometric tension recording. RA from DOCA-salt rats exhibited increased contraction to Up(4)A versus arteries from control uninephrectomized rats in the absence and presence of N(G)-nitro-l-arginine (nitric oxide synthase inhibitor). On the other hand, the Up(4)A-induced contraction in PA was similar between the two groups. Up(4)A-induced contraction was inhibited by suramin (nonselective P2 antagonist) but not by diinosine pentaphosphate pentasodium salt hydrate (Ip(5)I; P2X(1) antagonist) in RA from both groups. Furthermore, 2-thiouridine 5'-triphosphate tetrasodium salt (2-ThioUTP; P2Y(2) agonist)-, uridine-5'-(γ-thio)-triphosphate trisodium salt (UTPγS; P2Y(2)/P2Y(4) agonist)-, and 5-iodouridine-5'-O-diphosphate trisodium salt (MRS 2693; P2Y(6) agonist)-induced contractions were all increased in RA from DOCA-salt rats. Protein expression of P2Y(2)-, P2Y(4)-, and P2Y(6) receptors in RA was similar between the two groups. In DOCA-salt RA, the enhanced Up(4)A-induced contraction was reduced by PD98059, an ERK pathway inhibitor, and Up(4)A-stimulated ERK activation was increased. These data are the first to indicate that Up(4)A-induced contraction is enhanced in RA from DOCA-salt rats. Enhanced P2Y receptor signaling and activation of the ERK pathway together represent a likely mechanism mediating the enhanced Up(4)A-induced contraction. Up(4)A might be of relevance in the pathophysiology of vascular tone regulation and renal dysfunction in arterial hypertension.     

Lisinopril attenuates renal oxidative injury in l-NAME-induced hypertensive rats

Genetic factors related to cancer have been extensively studied and several polymorphisms have been associated to breast cancer. The FGFR4, MTHFR, and HFE genes have been associated with neoplastic diseases development. The current report outlines the analysis of the polymorphisms G388A (FGFR4), C677T (MTHFR), C282Y, and H63D (HFE) in Brazilian breast cancer patients. We studied 68 patients with invasive ductal and operable breast carcinoma and 85 women as a control group. The polymorphism frequencies in the breast cancer and control groups were analyzed, but no significant difference was observed by comparing the two groups. The presence of each polymorphism was analyzed according to the clinical features and markers already established as prognostic in the breast cancer group. The C677T, H63D, and G388A polymorphisms were not associated to histological grade, age of diagnosis, expression of HER2 receptor, or estrogen and progesterone receptor. The H63D polymorphism showed a significant association (P = 0.02) with the presence of p53 mutations, and C667T showed association to lymph node involvement (P = 0.05). Lymph node involvement, G388A polymorphism, and histological grade were independently associated to metastasis/death. Our data suggests that the polymorphisms G388A, C677T, and H63D are not useful in breast cancer diagnosis, but they may be significant additional prognostic markers related to breast cancer survival.     

Hemodynamic effects of long-term converting-enzyme inhibition in renal hypertensive rats

The hemodynamic effects of a converting-enzyme inhibitor (CEI) given during 12 consecutive hours were studied in severe chronic renal hypertensive and normotensive Wistar rats. Hemodynamic parameters were obtained by thermodilution method in conscious unrestrained animals twenty-four hours after surgery. A bolus of CEI induced a significant decrease of mean arterial pressure (MAP) (from 192.2 +/- 8.2 to 163.3 +/- 5.9 mmHg, p less than 0.001) and total peripheral resistance (TPR) (from 7.69 +/- 0.53 to 5.83 +/- 0.33 mmHg.min/ml 100 g) in hypertensive animals. Cardiac index (CI) and heart rate increased significantly (p less than 0.05). Infusion of CEI to hypertensive animals during 12 consecutive hours produced a further progressive decrease in MAP and TPR (p less than 0.05) and an increase in CI (p less than 0.05). Heart rate did not change. Acute and prolonged infusions of CEI to normotensive group induced less but similar effect to those observed in hypertensive group. These results suggest that an increase of the renin-angiotensin system activity is the principal mechanism involved in the maintenance of high blood pressure during chronic phase of renal hypertension on the rats.     

Endothelin in the splanchnic vascular bed of DOCA-salt hypertensive rats

Vascular capacitance is reduced by endothelin-1 (ET-1) in deoxycorticosterone (DOCA)-salt hypertensive rats. This may contribute to hypertension development. Because the splanchnic blood vessels (especially veins) are important in determining vascular capacitance, we tested the hypothesis that ET-1 levels in the splanchnic vasculature are elevated in hypertensive DOCA-salt compared with normotensive rats. Tissue ET-1 content was measured by ELISA in aorta, vena cava, superior mesenteric artery and vein, and small mesenteric arteries and veins from normotensive sham-operated (sham) and 4-wk DOCA-salt rats. We also determined ET-1 concentration in aortic and portal venous blood (draining the nonhepatic splanchnic organs) in anesthetized and conscious sham and DOCA-salt rats before and after acute blockade of ETB receptor-mediated plasma clearance of ET-1. Results showed a higher ET-1 content in veins than in arteries of similar size. However, ET-1 content was similar in vessels from sham and DOCA-salt rats, except in aorta and superior mesenteric artery, where ET-1 content was greater in DOCA-salt rats. ET-1 concentration was significantly higher in portal venous than in aortic blood, indicating net nonhepatic splanchnic release (nNHSR) of ET-1. However, nNHSR of ET-1 was similar in sham and DOCA-salt rats. Although nNHSR of ET-1 increased significantly after ETB receptor blockade in sham rats, it was completely unchanged in DOCA-salt rats. These data suggest that, despite the absence of ETB receptor-mediated plasma clearance of ET-1, neither the venous peptide content nor the net release of ET-1 is increased in the splanchnic vasculature of DOCA-salt rats. These results argue against the hypothesis that increased venomotor tone in DOCA-salt hypertension is caused by increased ET-1 concentration around splanchnic venous smooth muscle cells.     

Consumption of hydrogen-rich water alleviates renal injury in spontaneous hypertensive rats

The aim of this study was to investigate the inhibitory effect of a siRNA cocktail targeting Vascular endothelial growth factor (VEGF) and Human epidermal growth factor receptor 2 (HER2) on cell proliferation, induced apoptosis and the expression of VEGF and HER2 in human gastric carcinoma cell. The silencing rate of pre-designed siRNAs that targeted VEGF and HER2 was detected by Real-time Quantitative PCR (RT-QPCR) analysis. Furthermore, the best silencing siRNA that targeted VEGF and HER2 was prepared as a cocktail to co-knockdown VEGF and HER2 expression at both mRNA and protein levels which were detected by RT-QPCR and Western blot analysis. Cell proliferation inhibition rates were determined by CCK8 assay. The effect of siRNA cocktail on cell apoptosis was determined by flow cytometry. The migration inhibition of siRNA cocktail was analyzed by wound-healing assay. The ability of VEGF to induce endothelial cells to proliferate was examined in HUVECs by the method of tube formation assay. The pre-designed siRNAs could inhibit VEGF and HER2 mRNA level. siRNA cocktail, and co-downregulation of VEGF and HER2 result in significant inhibition of gastric cancer growth and migration in vitro. The inhibition of VEGF and HER2 expressions can induce apoptosis of SGC-7901 cells.     

Induction of hemeoxygenase-1 reduces glomerular injury and apoptosis in diabetic spontaneously hypertensive rats

Induction of hemeoxygenase-1 (HO-1) lowers blood pressure and reduces organ damage in hypertensive animal models; however, a potential protective role for HO-1 induction against diabetic-induced glomerular injury remains unclear. We hypothesize that HO-1 induction will protect against diabetes-induced glomerular injury by maintaining glomerular integrity and inhibiting renal apoptosis, inflammation, and oxidative stress. Diabetes was induced with streptozotocin in spontaneously hypertensive rats (SHR) as a model where the coexistence of hypertension and diabetes aggravates the progression of diabetic renal injury. Control and diabetic SHR were randomized to receive vehicle or the HO-1 inducer cobalt protoporphyrin (CoPP). Glomerular albumin permeability was significantly greater in diabetic SHR compared with control, consistent with an increase in apoptosis and decreased glomerular nephrin and α(3)β(1)-integrin protein expression in diabetic SHR. CoPP significantly reduced albumin permeability and apoptosis and restored nephrin and α(3)β(1)-integrin protein expression levels in diabetic SHR. Glomerular injury in diabetic SHR was also associated with increases in NF-κB-induced inflammation and oxidative stress relative to vehicle-treated SHR, and CoPP significantly blunted diabetes-induced increases in glomerular inflammation and oxidative stress in diabetic SHR. These effects were specific to exogenous stimulation of HO-1, since incubation with the HO inhibitor stannous mesoporphyrin alone did not alter glomerular inflammatory markers or oxidative stress yet was able to prevent CoPP-mediated decreases in these parameters. These data suggest that induction of HO-1 reduces diabetic induced-glomerular injury and apoptosis and these effects are associated with decreased NF-κB-induced inflammation and oxidative stress.     

Xanthine oxidase and mitochondria contribute to vascular superoxide anion generation in DOCA-salt hypertensive rats

Vascular superoxide anion (O(2)(*-)) levels are increased in DOCA-salt hypertensive rats. We hypothesized that the endothelin (ET)-1-induced generation of ROS in the aorta and resistance arteries of DOCA-salt rats originates partly from xanthine oxidase (XO) and mitochondria. Accordingly, we blocked XO and the mitochondrial oxidative phosphorylation chain to investigate their contribution to ROS production in mesenteric resistance arteries and the aorta from DOCA-salt rats. Systolic blood pressure rose in DOCA-salt rats and was reduced after 3 wk by apocynin [NAD(P)H oxidase inhibitor and/or radical scavenger], allopurinol (XO inhibitor), bosentan (ET(A/B) receptor antagonist), BMS-182874 (BMS; ET(A) receptor antagonist), and hydralazine. Plasma uric acid levels in DOCA-salt rats were similar to control unilaterally nephrectomized (UniNx) rats, reduced with allopurinol and bosentan, and increased with BMS. Levels of thiobarbituric acid-reacting substances were increased in DOCA-salt rats versus UniNx rats, and BMS, bosentan, and hydralazine prevented their increase. Dihydroethidium staining showed reduced O(2)(*-) production in mesenteric arteries and the aorta from BMS- and bosentan-treated DOCA-salt rats compared with untreated DOCA-salt rats. Increased O(2)(*-) derived from XO was reduced or prevented by all treatments in mesenteric arteries, whereas bosentan and BMS had no effect on aortas from DOCA-salt rats. O(2)(*-) generation decreased with in situ treatment by tenoyltrifluoroacetone and CCCP, inhibitors of mitochondrial electron transport complexes II and IV, respectively, whereas rotenone (mitochondrial complex I inhibitor) had no effect. Our findings demonstrate the involvement of ET(A) receptor-modulated O(2)(*-) derived from XO and from mitochondrial oxidative enzymes in arteries from DOCA-salt rats.     

Increased sympathetic venoconstriction and reactivity to norepinephrine in mesenteric veins in anesthetized DOCA-salt hypertensive rats

Increased sympathetic nervous activity (SNA) elevates venomotor tone in deoxycorticosterone acetate (DOCA)-salt hypertension. We studied the mechanisms by which the SNA increases venomotor tone in DOCA-salt hypertension by making in situ intracellular recordings of venous smooth muscle cell (VSMC) membrane potential (E(m)) and measurement of outside diameter (OD) in mesenteric veins (MV) and mesenteric arteries (MA) of anesthetized rats. We also studied norepinephrine (NE)- and endothelin-1 (ET-1)-induced increases in MA or MV perfusion pressure (PP) in vitro. E(m) in DOCA-salt MV was depolarized compared with sham MV. Prazosin hyperpolarized VSMC E(m) in DOCA-salt but not in sham MV. NE concentration-response curves (CRCs) for OD decreases in MV from DOCA-salt rats were left-shifted with an increased maximum response (E(max)) compared with sham MV. NE CRCs for OD decreases in MA were right-shifted with reduced E(max) in DOCA-salt compared with sham rats. ET-1 CRCs were similar in DOCA-salt and sham MV but were right-shifted with reduced E(max) in DOCA-salt MA. NE CRCs for MAPP increases were left-shifted without a change in E(max) in DOCA-salt rats. NE did not change MVPP. MAPP and MVPP for ET-1 CRCs were similar in sham and DOCA-salt rats, but E(max) for MAPP was reduced in DOCA-salt rats. Hematoxylin staining revealed hypertrophy in DOCA-salt MA but not in MV. We conclude that there is increased reactivity to NE released from the sympathetic nervous system in DOCA-salt MV that causes VSMC depolarization and increased venomotor tone. In DOCA-salt rats, in vivo ET-1 reactivity is maintained in MV, but reduced in MA.     

Local delivery of soluble TNF-alpha receptor 1 gene reduces infarct size following ischemia/reperfusion injury in rats

Apoptosis in the myocardium is linked to ischemia/reperfusion injury, and TNF-alpha induces apoptosis in cardiomyocytes. A significant amount of TNF-alpha is detected after ischemia and reperfusion. Soluble TNF-alpha receptor 1 (sTNFR1) is an extracellular domain of TNF-alpha receptor 1 and is an antagonist to TNF-alpha. In the present study, we examined the effects of sTNFR1 on infarct size in acute myocardial infarction (AMI) following ischemia/reperfusion. Male Wistar rats were subjected to left coronary artery (LCA) ligation. After 30 min of LCA occlusion, the temporary ligature on the LCA was released and blood flow was restored. Immediately after reperfusion, a total of 200 microg of sTNFR1 or LacZ plasmid was injected into three different sites of the left ventricular wall. At 6 h, 1 and 2 days after reperfusion, the TNF-alpha bioactivity in the myocardium was significantly higher in rats receiving LacZ plasmid than in sham-operated rats, whereas sTNFR1 plasmid significantly suppressed the increase in the TNF-alpha bioactivity. The sTNFR1 plasmid significantly reduced DNA fragmentation and caspase activity compared to the LacZ plasmid. Finally, the sTNFR1 expression-plasmid treatment significantly reduced the area of myocardial infarction at 2 days after ischemia/reperfusion compared to LacZ plasmid. In conclusion, the TNF-alpha bioactivity in the heart increased from the early stage of ischemia/reperfusion, and this increase was thought to contribute in part to the increased area of myocardial infarction. Suppression of TNF-alpha bioactivity with the sTNFR1 plasmid reduced the infarct size in AMI following ischemia and reperfusion.     

Endothelin-1 contributes to the sexual differences in renal damage in DOCA-salt rats

We investigated whether gender differences in renal damage in DOCA-salt hypertension are associated with effects of ovarian hormones and/or endothelin-1 (ET-1). Renal injuries and renal pre-pro-ET-1 mRNA expression were enhanced in male and female ovariectomized (OVX) DOCA rats versus female DOCA rats. Treatment with estrogen plus progesterone or progesterone, but not estrogen alone, attenuated renal damage and pre-pro-ET-1 mRNA expression in OVX DOCA rats. The ETA antagonist BMS182874 greatly ameliorated renal damage in male and OVX DOCA rats. In conclusion, the ovarian hormones have a protective role on the renal structural alterations in female DOCA rats by modulating effects of ET-1, via ETA receptors.     

Morphological and biochemical characterization of remodeling in aorta and vena cava of DOCA-salt hypertensive rats

Arterial remodeling occurs in response to mechanical and neurohumoral stimuli. We hypothesized that veins, which are not exposed to higher pressures in hypertension, would demonstrate less active remodeling than arteries. We assessed remodeling with two standard measures of arterial remodeling: vessel morphometry and the expression/function of matrix metalloproteinases (MMPs). Thoracic aorta and vena cava from sham normotensive and DOCA-salt hypertensive rats (110 +/- 4 and 188 +/- 8 mmHg systolic blood pressure, respectively) were used. Wall thickness was increased in DOCA-salt vs. sham aorta (301 +/- 23 vs. 218 +/- 14 mum, P < 0.05), as was medial area, but neither measure was altered in the vena cava. The aorta and vena cava expressed the gelatinases MMP-2, MMP-9, transmembrane proteinase MT1-MMP, and tissue inhibitor of metalloproteinase-2 (TIMP-2). Immunohistochemically, MMP-2 localized to smooth muscle in the aorta and densely in endothelium/smooth muscle of the vena cava. Western and zymographic analyses verified that MMP-2 was active in all vessels and less active in the vena cava than aorta. In hypertension, MMP-2 expression and activity in the aorta were increased (59.1 +/- 3.7 and 74.5 +/- 6.1 units in sham and DOCA, respectively, P < 0.05); similar elevations were not observed in the vena cava. MMP-9 was weakly expressed in all vessels. MT1-MMP was expressed by the aorta and vena cava and elevated in the vena cava from DOCA-salt rats. TIMP-2 expression was significantly increased in the aorta of DOCA rats compared with sham but was barely detectable in the vena cava of sham or DOCA-salt hypertensive rats. These findings suggest that large veins may not undergo vascular remodeling in DOCA-salt hypertension.     

Progesterone reduces erectile dysfunction in sleep-deprived spontaneously hypertensive rats

Background

The rate-limiting step in prostaglandin (PG) biosynthesis is catalyzed by phospholipase A2 (PLA2) enzymes which hydrolyze arachidonic acid from membrane phospholipids. Despite their importance in uterine PG production, little is known concerning the specific PLA2 enzymes that regulate arachidonic acid liberation in the uterine endometrium. The objectives of this study were to evaluate the expression and activities of calcium-independent Group VI and Group IVC PLA2 (PLA2G6 and PLA2G4C) and calcium-dependent Group IVA PLA2 (PLA2G4A) enzymes in the regulation of bovine uterine endometrial epithelial cell PG production.

Methods

Bovine endometrial epithelial cells in culture were treated with oxytocin, interferon-tau and the PLA2G6 inhibitor bromoenol lactone, alone and in combination. Concentrations of PGF2alpha and PGE2 released into the medium were analyzed. Western blot analysis was performed on cellular protein to determine the effects of treatments on expression of PLA2G4A, PLA2G6 and PLA2G4C. Group-specific PLA2 activity assays were performed on cell lysates following treatment with oxytocin, interferon-tau or vehicle (control), alone and in combination. To further evaluate the role of specific PLA2 enzymes in uterine cell PG biosynthesis, cells were transfected with cDNAs encoding human PLA2G6 and PLA24C, treated as described above and PG assays performed.

Results

Constitutive cell production of PGF2alpha was about two-fold higher than PGE2. Oxytocin stimulated production of both PGs but the increase of PGF2alpha was significantly greater. Interferon-tau diminished oxytocin stimulation of both PGs. The PLA2G6 inhibitor, bromoenol lactone, abolished oxytocin-stimulated production of PGF2alpha. Treatments had little effect on PLA2G4A protein expression. In contrast, oxytocin enhanced expression of PLA2G6 and this effect was diminished in the presence of interferon-tau. Expression of PLA2G4C was barely detectable in control and oxytocin treated cells but it was enhanced in cells treated with interferon-tau. Oxytocin stimulated PLA2 activity in assays designed to evaluate PLA2G6 activity and interferon-tau inhibited this response. In assays designed to measure PLA2G4C activity, only interferon-tau was stimulatory. Cells overexpressing PLA2G6 produced similar quantities of the two PGs and these values were significantly higher than PG production by non-transfected cells. Oxytocin stimulated production of both PGs and this response was inhibited by interferon-tau. Bromoenol lactone inhibited oxtocin stimulation of PGF2alpha production but stimulated PGE2 production, both in the absence and presence of oxytocin. Cells over-expressing PLA2G4C produced more PGE2 than PGF2alpha and interferon-tau stimulated PGE2 production.

Conclusion

Results from these studies indicate that oxytocin stimulation of uterine PGF2alpha production is mediated, at least in part, by up-regulation of PLA2G6 expression and activity. In addition to its known inhibitory effect on oxytocin receptor expression, interferon-tau represses oxytocin-stimulated PLA2G6 expression and activity and this contributes to diminished PGF2alpha production. Furthermore, endometrial cell PGE2 biosynthesis was associated with PLA2G4C expression and activity and interferon-tau was stimulatory to this process.     

Progesterone reduces erectile dysfunction in sleep-deprived spontaneously hypertensive rats

Background  

Paradoxical sleep deprivation (PSD) associated with cocaine has been shown to enhance genital reflexes (penile erection-PE and ejaculation-EJ) in Wistar rats. Since hypertension predisposes males to erectile dysfunction, the aim of the present study was to investigate the effects of PSD on genital reflexes in the spontaneously hypertensive rat (SHR) compared to the Wistar strain. We also extended our study to examine how PSD affect steroid hormone concentrations involved in genital events in both experimental models.     

Effects of Melothriamaderaspatana leaf extract on antioxidant status in sham-operated and uninephrectomized DOCA-salt hypertensive rats

The present study was designed to investigate the antihypertensive and antioxidant effect of Melothria maderaspatana leaf extract (MME) on sham-operated and DOCA-salt (deoxycorticosterone acetate) induced hypertensive rats. Administration of DOCA-salt significantly increased the systolic (from 127 to 212 mm Hg) and diastolic (from 91 to 174 mm Hg) blood pressure compared to sham-operated control rats, while treatment with MME significantly reduced the systolic (from 212 to 135 mm Hg) and diastolic (from 174 to 96 mm Hg) blood pressure compared to hypertensive control. In DOCA-salt rats, the plasma and tissue concentration of thiobarbituric acid reactive substances (TBARS) and lipid hydroperoxide (LOOH) significantly increased and administration of MME significantly reduced these parameters towards the levels in sham-operated control. In hypertensive rats, activities of the enzymatic antioxidants such as superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) and levels of non-enzymatic antioxidants such as vitamin C, vitamin E and reduced glutathione (GSH) decreased significantly in the plasma and tissues. Administration of MME returned the enzymatic and non-enzymatic antioxidants towards sham-operated control. MME shows both antihypertensive and antioxidant properties in DOCA-salt hypertensive rats and, among the three different doses tested, 200 mg/kg caused the maximum effect.     

Minerals in renal and SHR hypertensive rats

References to individual trace minerals in hypertensive rats have been made; however, data on multiple minerals in SHR hypertensive rats is lacking. The purpose of this study was to investigate five trace minerals in normotensive, chronic renal and SHR hypertensive rats. Blood samples were drawn to measure serum levels of Ca, Fe, K, Mg, and Na. Serum K values were elevated in the chronic renal hypertensive animals. Iron levels were decreased in both the renal and SHR hypertensive animals. No difference was observed in levels of Ca, Mg, and Na between normotensive and chronic renal or SHR hypertensive rats. Further study of multiple trace minerals in experimental hypertension is recorded in order to extend these deviations.     

In vivo and in vitro magnesium effects on aortic prostacyclin generation in DOCA-salt hypertensive rats.

To investigate the blood pressure lowering effect of magnesium (Mg2+) in the hypertensive rat, we measured the prostacyclin release (PGI2, as immunoreactive 6-keto-PGF1 alpha) by isolated aortae from normotensive and deoxycorticosterone acetate (DOCA)-salt hypertensive rats fed a control or Mg(2+)-enriched diet. We also studied the in vitro effect of Mg2+ on aortic PGI2 release. The Mg(2+)-enriched diet significantly decreased by 10% blood pressure in DOCA-salt hypertensive rats but not in normotensive rats. The Mg(2+)-enriched diet significantly increased by 122% aortic PGI2 release in DOCA-salt hypertensive rats, but not in normotensive rats. Mg2+ supplementation in the incubation medium (4.8 mM) significantly increased aortic PGI2 release by 94% in DOCA-salt hypertensive rats, but not in normotensive rats. These data suggest that the Mg(2+)-induced attenuation of blood pressure in DOCA-salt hypertensive rats could be linked with the enhanced vascular PGI2 release.