Magnesium supplementation and deoxycorticosterone acetate--salt hypertension: effect on arterial mechanical properties and on activity of endothelin-1

The aim of this study was to show whether the decrease in blood pressure induced by Mg supplementation in deoxycorticosterone acetate - salt (DOCA-salt) hypertensive rats is associated with mechanical modifications of blood vessels and (or) changes in tissular production and (or) vasoconstrictor activity to endothelin-1. DOCA-salt treatment increased blood pressure, media thickness, cross-sectional area, and lumen diameter of carotid arteries. Distensibility and incremental elastic modulus versus stress were not altered in carotid arteries, suggesting that the DOCA-salt vessel wall adapts structurally to preserve its blood pressure buffering capacity. Magnesium supplementation attenuated DOCA-salt hypertension. In comparison with normotensive rats, systolic, mean, and pulse pressures were higher whereas diastolic pressure was not different in Mg-supplemented DOCA-salt rats. Magnesium supplementation did not significantly modify the elastic parameters of carotid arteries. In resistance mesenteric arteries, DOCA-salt hypertension induces an inward hypertrophic remodeling. Magnesium supplementation attenuates wall hypertrophy and increases lumen diameter to the normotensive diameter, suggesting a decrease in peripheral resistance. Magnesium supplementation normalizes the altered vasoconstrictor activity of endothelin-1 in mesenteric arteries and attenuates endothelin-1 overproduction in kidney, left ventricle, and aorta of DOCA-salt rats. These findings suggest that Mg supplementation prevents blood pressure elevation by attenuating peripheral resistance and by decreasing hypertrophic effect of endothelin-1 via inhibition of endothelin-1 production.     

Age-dependent effect of oxidative stress on cardiac sarcoplasmic reticulum vesicles

The oxidative stress hypothesis of aging suggests that accumulation of oxidative damage is a key factor of the alterations in physiological function during aging. We studied age-related sensitivity to oxidative modifications of proteins and lipids of cardiac sarcoplasmic reticulum (SR) isolated from 6-, 15- and 26-month-old rats. Oxidative stress was generated in vitro by exposing SR vesicles to 0.1 mmol/l FeSO4/EDTA + 1 mmol/l H2O2 at 37 degrees C for 60 min. In all groups, oxidative stress was associated with decreased membrane surface hydrophobicity, as detected by 1-anilino-8-naphthalenesulfonate as a probe. Structural changes in SR membranes were accompanied by degradation of tryptophan and significant accumulation of protein dityrosines, protein conjugates with lipid peroxidation products, conjugated dienes and thiobarbituric acid reactive substances. The sensitivity to oxidative damage was most pronounced in SR of 26-month-old rat. Our results indicate that aging and oxidative stress are associated with accumulation of oxidatively damaged proteins and lipids and these changes could contribute to cardiovascular injury.     

Prolonged isobaric relaxation time in small mesenteric arteries of the spontaneously hypertensive rat

Prolonged isometric relaxation in hypertensive aortic and caudal arterial smooth muscle has been demonstrated; however, isobaric relaxation in resistance arteries is more pertinent to studies in hypertension. A comparative study of mesenteric arterial isobaric relaxation times was made using spontaneously hypertensive rats (SHR), normotensive Wistar-Kyoto rats (WKY), and MK-421 treated SHR (treatment commenced at 8 weeks of age and was maintained until sacrifice). Relaxation rates of vessels constricting against a range of pressures and achieving different degrees of narrowing or changes in circumference were analyzed. Comparisons were made between SHR, WKY, and MK-421 treated SHR arteries that had constricted from the same initial circumference and against the same magnitude of pressure. The SHR mesenteric arteries relaxed at a slower rate than did the WKY vessels. The normotensive MK-421 treated SHR showed the same prolonged relaxation rate as did the untreated SHR preparations. Thus the slower rate of relaxation in SHR arteries does not appear to be a consequence of the hypertension. Such prolonged time for narrowing would function to increase the average peripheral resistance and thus may contribute to the initiation and maintenance of increased blood pressure.     

Relationship between antioxidant potential and oxidative damage to lipids, proteins and DNA in aged rats

Oxidative stress has been implicated to play a major role in aging and age-related diseases. In the present study, we investigated the effects of aging on the total antioxidant capacity, uric acid, lipid peroxidation, total sulfhydryl group content and damage to DNA in adult (6 months), old (15 months) and senescent (26 months) male Wistar rats. The antioxidant capacity, determined by phycoerythrin-based TRAP method (total peroxyl radical-trapping potential) was significantly decreased in the plasma and myocardium of old and senescent rats, whereas plasma level of uric acid was elevated in 26-month-old rats. Age-related decline in plasma and heart antioxidant capacity was accompanied by a significant loss in total sulfhydryl group content, increased lipid peroxidation and higher DNA damage in lymphocytes. Correlations between TRAP and oxidative damage to lipids, proteins and DNA suggest that the decline in antioxidant status may play an important role in age-related accumulation of cell damage caused by reactive oxygen species.     

Heterogeneity in Arterial Remodeling among Sublines of Spontaneously Hypertensive Rats

Objectives

Spontaneously hypertensive rats (SHR) have been used frequently as a model for human essential hypertension. However, both the SHR and its normotensive control, the Wistar Kyoto rat (WKY), consist of genetically different sublines. We tested the hypothesis that the pathophysiology of vascular remodeling in hypertension differs among rat sublines.

Methods and Results

We studied mesenteric resistance arteries of WKY and SHR from three different sources, at 6 weeks and 5 months of age. Sublines of WKY and SHR showed differences in blood pressure, body weight, vascular remodeling, endothelial function, and vessel ultrastructure. Common features in small mesenteric arteries from SHR were an increase in wall thickness, wall-to-lumen ratio, and internal elastic lamina thickness.

Conclusions

Endothelial dysfunction, vascular stiffening, and inward remodeling of small mesenteric arteries are not common features of hypertension, but are subline-dependent. Differences in genetic background associate with different types of vascular remodeling in hypertensive rats.     

Calcium dynamics and vasomotion in arteries subject to isometric, isobaric, and isotonic conditions

In vitro, different techniques are used to study the smooth muscle cells’ calcium dynamics and contraction/relaxation mechanisms on arteries. Most experimental studies use either an isometric or an isobaric setup. However, in vivo, a blood vessel is neither isobaric nor isometric nor isotonic, as it is continuously submitted to intraluminal pressure variations arising from heart beat. We use a theoretical model of the smooth muscle calcium and arterial radius dynamics to determine whether results may be considerably different depending on the experimental conditions (isometric, isobaric, isotonic, or cyclic pressure variations). We show that isobaric conditions appear to be more realistic than isometric or isotonic situations, as the calcium dynamics is similar under cyclic intraluminal pressure variations (in vivo-like situation) and under a constant pressure (isobaric situation). The arterial contraction is less pronounced in isotonic than in isobaric conditions, and the vasoconstrictor sensitivity higher in isometric than isobaric or isotonic conditions, in agreement with experimental observations. Interestingly, the model predicts that isometric conditions may generate artifacts like the coexistence of multiple stable states. We have verified this model prediction experimentally using rat mesenteric arteries mounted on a wire myograph and stimulated with phenylephrine.     

Age-related alterations in NOS and oxidative stress in mesenteric arteries from male and female rats.

Epidemiological evidence suggests that advancing age affects the cardiovascular system of men and women differently. The purpose of this study was to determine whether the effects of aging on nitric oxide synthase (NOS), oxidative stress, and vascular function are different in males and females. Mesenteric arteries from young (3 mo) and old (24 mo) male and female Fischer 344/Brown Norway rats were studied. Western blot analysis and NOS activity were performed on the homogenized mesenteric arterial bed separated into cytosolic and membrane-associated fractions. Plasma 8-isoprostane measurements assessed oxidative stress. Vascular reactivity was determined by using a wire myograph in the absence and presence of a NOS inhibitor, N(omega)-nitro-l-arginine, to examine endothelial function and basal and stimulated nitric oxide release. In additional arteries, reactivity was performed in the presence of polyethylene glycol-SOD to assess the impact of superoxide on vascular function. Among females, aging was associated with a decline in membrane-associated NOS activity and membrane-associated NOS III protein expression. Advancing age in males was associated with increased cytosolic NOS III protein expression. Among both males and females, advancing age resulted in increased oxidative stress. Vascular function was maintained with age in arteries from both males and females, and there was no difference in either basal or stimulated nitric oxide release with age. Despite sex-specific effects of advancing age on the NOS system and increases in markers of oxidative stress, vascular function is maintained in mesenteric arteries from aged Fischer 344/Brown Norway rats. These data suggest that age-related alterations in the resistance vasculature are complex and likely involve multiple compensating vasoactive pathways.     

Hepatic Oxidative Stress,Genotoxicity and Vascular Dysfunction in Lean or Obese Zucker Rats

Metabolic syndrome is associated with increased risk of cardiovascular disease, which could be related to oxidative stress. Here, we investigated the associations between hepatic oxidative stress and vascular function in pressurized mesenteric arteries from lean and obese Zucker rats at 14, 24 and 37 weeks of age. Obese Zucker rats had more hepatic fat accumulation than their lean counterparts. Nevertheless, the obese rats had unaltered age-related level of hepatic oxidatively damaged DNA in terms of formamidopyrimidine DNA glycosylase (FPG) or human oxoguanine DNA glycosylase (hOGG1) sensitive sites as measured by the comet assay. There were decreasing levels of oxidatively damaged DNA with age in the liver of lean rats, which occurred concurrently with increased expression of Ogg1. The 37 week old lean rats also had higher expression level of Hmox1 and elevated levels of DNA strand breaks in the liver. Still, both strain of rats had increased protein level of HMOX-1 in the liver at 37 weeks. The external and lumen diameters of mesenteric arteries increased with age in obese Zucker rats with no change in media cross-sectional area, indicating outward re-modelling without hypertrophy of the vascular wall. There was increased maximal response to acetylcholine-mediated endothelium-dependent vasodilatation in both strains of rats. Collectively, the results indicate that obese Zucker rats only displayed a modest mesenteric vascular dysfunction, with no increase in hepatic oxidative stress-generated DNA damage despite substantial hepatic steatosis.     

Biomechanical response of arterial wall to DOCA-salt hypertension in growing and middle-aged rats

To study arterial remodeling in response to hypertension, Deoxycortico-sterone acetate (DOCA)-salt hypertension was induced in immature (aged 16 weeks) and middle-aged (48 weeks) rats, and biomechanical properties and wall dimensions of common carotid arteries were determined. Arterial segments were excised at 10 or 16 weeks postoperatively from the immature rats and at 16 weeks from the middle-aged ones. In vitro pressure-diameter tests were performed under normal (in Krebs-Ringer solution), active (norepinephrine), and passive (papaverine) conditions. Non-treated, age-matched rats (26, 32, and 64 weeks) were used to obtain control data. Wall thickness at in vivo blood pressure level was increased by hypertension at all ages; however, there were no significant changes in inner diameter. In hypertensive rats, arterial outer diameter was smaller under normal condition than under passive condition, indicating the increase of smooth muscle tone by hypertension. Diameter reduction developed by norepinephrine was increased by hypertension, which was significant above 100 mmHg; however, there were no significant differences between hypertensive and normotensive arteries, if compared at respective in vivo blood pressures. No significant differences were observed in wall stiffness at in vivo pressure. Wall hoop stress at in vivo blood pressure had a significant positive correlation with the pressure in 26-week old arteries. However, there were no differences in the stress between hypertension and normotension in 32- and 64-week old arteries. These results were essentially similar to previous ones observed in Goldblatt hypertension and in younger animals. Age-related differences in arterial wall remodeling were not clearly observed.     

Senolytics prevent caveolar CaV3.2-RyR axis malfunction in old vascular smooth muscle

Aging is a major risk factor for cardiovascular diseases. Our previous studies demonstrate that aging impairs the caveolar T-type Ca_V3.2-RyR axis for extracellular Ca²⁺ influx to trigger Ca²⁺ sparks in vascular smooth muscle cells (VSMCs). We hypothesize that the administration of senolytics, which can selectively clear senescent cells, could preserve the caveolar Ca_V3.2-RyR axis in aging VSMCs. In this study, 10-month-old mice were administered the senolytics cocktail consisting of dasatinib (5 mg/kg) and quercetin (50 mg/kg) or vehicle bi-weekly for 4 months. Using VSMCs from mouse mesenteric arteries, we found that Ca²⁺ sparks were diminished after caveolae disruption by methyl-β-cyclodextrin (10 mM) in cells from D + Q treated but not vehicle-treated 14-month-old mice. D + Q treatment promoted the expression of Ca_V3.2 in 14-month-old mesenteric arteries. Structural analysis using electron tomography and immunofluorescence staining revealed the remodeling of caveolae and co-localization of Ca_V3.2-Cav-1 in D + Q treatment aged mesenteric arteries. In keeping with theoretical observations, Ca_v3.2 channel inhibition by Ni²⁺ (50 μM) suppressed Ca²⁺ in VSMCs from the D + Q group, with no effect observed in vehicle-treated arteries. Our study provides evidence that age-related caveolar Ca_V3.2-RyR axis malfunction can be alleviated by pharmaceutical intervention targeting cellular senescence. Our findings support the potential of senolytics for ameliorating age-associated cardiovascular disease.     

Production of endothelin-1 from the mesenteric arteries of streptozotocin-induced diabetic rats

Release of endothelin-1 (ET-1) from the mesenteric arteries of Wistar rats with streptozotocin-induced diabetes (STZ-DM) rats and nondiabetic rats was measured by a specific enzyme immunoassay following purification using an immunoaffinity column. The mesenteric arteries from STZ-DM rats released a significantly higher amount of ET-1 as compared to control rats (35.8 +/- 2.8 vs 14.9 +/- 2.0 pg/1hr, p less than 0.05). The plasma level of ET-1 in STZ-DM rats was also elevated to a significant extent as compared to controls (5.1 +/- 0.4 vs 3.0 +/- 0.4 pg/ml, p less than 0.05). The systolic blood pressure of STZ-DM rats was significantly higher than of the controls (p less than 0.05). The increased level of plasma ET-1 as well as its release from the mesenteric artery of STZ-DM rats may suggest its release following damage to the endothelium caused by diabetes and/or by associated changes in blood pressure.     

Aging alters the functional expression of enzymatic and non-enzymatic anti-oxidant defense systems in testicular rat Leydig cells

In aged rats, trophic hormone-stimulated testosterone secretion by isolated Leydig cells is greatly reduced. The current studies were initiated to establish a functional link between excess oxidative stress and the age-related decline in steroidogenesis. Highly purified Leydig cell preparations obtained from 5-month (young mature) and 24-month (old) Sprague-Dawley rats were employed to measure and compare levels of lipid peroxidation, non-enzymatic (alpha-tocopherol, ascorbic acid, and reduced/oxidized glutathione) and enzymatic (Cu, Zn-superoxide dismutase, Cu, Zn-SOD; Mn-superoxide dismutase, Mn-SOD; glutathione peroxidase-1, GPX-1, and catalase, CAT) anti-oxidants. The extent of lipid peroxidation (oxidative damage) in isolated membrane fractions was quantified by measuring the content of thiobarbituric acid-reactive substances (TBARS) under basal conditions, or in the presence of non-enzymatic or enzymatic pro-oxidants. Membrane preparations isolated from Leydig cells from old rats exhibited two- to three-fold enhancement of basal TBARS formation. However, aging had no significant effect on TBARS formation in response to either non-enzymatic or enzymatic pro-oxidants. Among the non-enzymatic anti-oxidants, the levels of reduced glutathione were drastically reduced during aging, while levels of alpha-tocopherol and ascorbic acid remained unchanged. Both steady-state mRNA levels and catalytic activities of Cu, Zn-SOD, Mn-SOD, and GPX-1 were also significantly lower in Leydig cells from 24-month-old rats as compared with 5-month-old control rats. In contrast, neither mRNA levels nor enzyme activity of catalase was sensitive to aging. From these data we conclude that aging is accompanied by reduced expression of key enzymatic and non-enzymatic anti-oxidants in Leydig cells leading to excessive oxidative stress and enhanced oxidative damage (lipid peroxidation). It is postulated that such excessive oxidative insult may contribute to the observed age-related decline in testosterone secretion by testicular Leydig cells.     

Increased microparticle production and impaired microvascular endothelial function in aldosterone-salt-treated rats: protective effects of polyphenols

We aimed to characterize circulating microparticles in association with arterial stiffness, inflammation and endothelial dysfunction in aldosterone-salt-induced hypertension in rats and to investigate the preventive effects of red wine polyphenols. Uninephrectomized male Sprague-Dawley rats were treated with aldosterone-salt (1 µg.h⁻¹), with or without administration of either red wine polyphenols, Provinols™ (20 mg.kg⁻¹.day⁻¹), or spironolactone (30 mg.kg⁻¹.day⁻¹) for 4 weeks. Microparticles, arterial stiffness, nitric oxide (NO) spin trapping, and mesenteric arterial function were measured. Aldosterone-salt rats showed increased microparticle levels, including those originating from platelets, endothelium and erythrocytes. Hypertension resulted in enhanced aortic stiffness accompanied by increased circulating and aortic NO levels and an upregulation of aortic inducible NO-synthase, NFκB, superoxide anions and nitrotyrosine. Flow-induced dilatation was reduced in mesenteric arteries. These effects were prevented by spironolactone. Provinols™ did not reduce arterial stiffness or systolic hypertension but had effects similar to those of spironolactone on endothelial function assessed by flow-mediated vasodilatation, microparticle generation, aortic NO levels and oxidative stress and apoptosis in the vessel wall. Neither the contractile response nor endothelium-dependent relaxation in mesenteric arteries differed between groups. The in vivo effects of Provinols™ were not mediated by mineralocorticoid receptors or changes in shear stress. In conclusion, vascular remodelling and endothelial dysfunction in aldosterone-salt-mediated hypertension are associated with increased circulating microparticles. Polyphenols prevent the enhanced release of microparticles, macrovascular inflammation and oxidative stress, and microvascular endothelial dysfunction independently of blood pressure, shear stress and mineralocorticoid receptor activation in a model of hyperaldosteronism.     

Myogenic reactivity is reduced in small renal arteries isolated from relaxin-treated rats

Administration of the ovarian hormone relaxin to nonpregnant rats vasodilates the renal circulation comparable to pregnancy. This vasodilation is mediated by endothelin (ET), the ET(B) receptor, and nitric oxide. Furthermore, endogenous relaxin mediates the renal vasodilation and hyperfiltration that occur during gestation. The goal of this study was to investigate whether myogenic reactivity of small renal and mesenteric arteries is reduced in relaxin-treated rats comparable to the pregnant condition. Relaxin or vehicle was administered to virgin female Long-Evans rats for 5 days at 4 microg/h, thereby producing midgestational blood levels of the hormone. The myogenic responses of small renal arteries (200-300 microm in diameter) isolated from these animals were evaluated in an isobaric arteriograph system. Myogenic reactivity was significantly reduced in the small renal arteries from relaxin-treated compared with vehicle-treated rats. The reduced myogenic responses were mediated by the ET(B) receptor and nitric oxide since the selective ET(B) receptor antagonist RES-701-1 and the nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester restored myogenic reactivity to virgin levels. The influence of relaxin was not limited to the renal circulation because myogenic reactivity was also reduced in small mesenteric arteries isolated from relaxin-treated rats. Thus relaxin administration to nonpregnant rats mimics pregnancy, insofar as myogenic reactivity of small renal and mesenteric arteries is reduced in both conditions.     

Age-related changes in the contractile and passive arterial properties of murine mesenteric small arteries are altered by caveolin-1 knockout

Caveolin-1, an integral protein of caveolae, is associated with multiple cardiovascular signalling pathways. Caveolin-1 knockout (KO) mice have a reduced lifespan. As changes in artery structure and function are associated with ageing we have investigated the role of caveolin-1 ablation on age-related changes of small artery contractility and passive mechanical properties. Mesenteric small arteries isolated from 3 and 12-month wild-type (WT) and caveolin-1 KO mice were mounted on a pressure myograph and changes in passive and functional arterial properties were continuously monitored. In WT mice ageing was associated with a reduction in arterial contractility to noradrenaline which was reversed by inhibition of nitric oxide synthase with L-NNA. Similarly, in 3-month-old mice, caveolin-1 KO reduced contractility to noradrenaline by an L-NNA-sensitive mechanism. However, ageing in caveolin-1 KO mice was not associated with any further change in contractility. In WT mice ageing was associated with an increased passive arterial diameter and cross-sectional area (CSA), consistent with outward remodelling of the arterial wall, and a reduced arterial distensibility. Caveolin-1 ablation at 3 months of age resulted in similar changes in passive arterial properties to those observed with ageing in WT animals. However, ageing in caveolin-1 KO mice resulted in a reduced arterial CSA indicating different effects on passive structural characteristics from that observed in WT mice. Thus, caveolin-1 mice show abnormalities of small mesenteric artery function and passive mechanical characteristics indicative of premature vascular ageing. Moreover, caveolin-1 ablation modulates the age-related changes usually observed in mesenteric arteries of WT mice.     

Estrogen replacement increases coronary artery distensibility in ovariectomized rats.

The effect of estrogen on the passive characteristics of arteries is not known. We hypothesized that estrogen would increase arterial distensibility as part of its protective effect on the vasculature. Female Sprague-Dawley rats were ovariectomized at 11 weeks of age. One group received a placebo (n = 6), while two other groups (n = 5 each) of rats received a 17beta-estradiol pellet (0.15 mg or 0.5 mg with 60-day release). After 4 weeks of estrogen replacement, coronary and mesenteric arteries (<200 microm diameter) were dissected and mounted on a dual-chamber arteriograph. Lumen diameter and wall thickness were measured in pressurized arteries. The relative changes in diameter (distensibility) as well as wall thickness per unit change in pressure were significantly increased (p < 0.05) in the coronary arteries of the 0.5 mg estradiol replaced rats compared with the ovariectomized control animals and the 0.15 mg estradiol replaced rats. Surprisingly, in the mesenteric arteries from the same animals, there was no difference in distensibility or pressure - wall thickness among the groups. This study provides experimental data of a novel hypothesis that estrogen may afford part of its protection through vascular remodeling of the coronary circulation.     

Alpha 1 adrenergic receptor control of renal blood vessels during aging

Aging humans and rats have a reduced renal vascular constriction response to stress, change in posture, or exercise. In this study, renal interlobar arteries from 9- (intermediate age) to 15-month-old (aging) male Wistar rats constricted less to alpha-adrenergic agonists than those of 4-month-old (young adult) rats. The reduced contraction to A61603 (alpha 1 A agonist) was similar to that to norepinephrine and phenylephrine. Therefore, it appears that the reduction in constriction is primarily related to alpha 1 A receptor stimulation. GeneChip microarray hybridization analysis of the interlobar arteries with the RAE 230A GeneChip indicated that there were no significant differences in gene expression for alpha 1 A/C, 1B, or 1D receptors between 4-month-old (young adult) and 1-year-old (aging) male Wistar rats. Competitive binding experiments (prazosin) revealed that maximal binding (Bmax, fmol/mg protein) of the alpha 1 receptors of interlobar arteries was reduced 25% by 10 months of age and 50% by 18+ months of age. Alpha 1 receptor-induced arterial constriction and prazosin binding were both down-regulated. The loss of receptor-initiated constriction likely includes down-regulation of maximum agonist binding by alpha 1 adrenergic receptors.     

Effects of aging on activities of mitochondrial electron transport chain complexes and oxidative damage in rat heart

Mitochondrial dysfunction and accumulation of oxidative damage have been implicated to be the major factors of aging. However, data on age-related changes in activities of mitochondrial electron transport chain (ETC) complexes remain controversial and molecular mechanisms responsible for ETC dysfunction are still largely unknown. In this study, we examined the effect of aging on activities of ETC complexes and oxidative damage to proteins and lipids in cardiac mitochondria from adult (6-month-old), old (15-month-old) and senescent (26-month-old) rats. ETC complexes I-IV displayed different extent of inhibition with age. The most significant decline occurred in complex IV activity, whereas complex II activity was unchanged in old rats and was only slightly reduced in senescent rats. Compared to adult, old and senescent rat hearts had significantly higher levels of malondialdehyde, 4-hydroxynonenal (HNE) and dityrosine, while thiol group content was reduced. Despite marked increase in HNE content with age (25 and 76 % for 15- and 26-month-old rats, respectively) Western blot analysis revealed only few HNE-protein adducts. The present study suggests that non-uniform decline in activities of ETC complexes is due, at least in part, to mitochondrial oxidative damage; however, lipid peroxidation products appear to have a limited impact on enzyme functions.     

Dietary soy modulates endothelium-dependent relaxation in aged male rats: Increased agonist-induced endothelium-derived hyperpolarising factor and basal nitric oxide activity

We examined the effects of dietary soy on the contributions of endothelium-derived hyperpolarising factor (EDHF), nitric oxide (NO), and oxidative stress to vascular tone in isolated aortic rings and small mesenteric and pulmonary arteries in vitro. Male Wistar rats were either continuously fed a soy-deficient diet (SD) or switched from a soy-deficient diet to a soy-rich one for 6 months (SW). Contractile responses were generally smaller in arteries from SW rats. In mesenteric arteries, this difference was blunted by L-NAME, but not by charybdotoxin and apamin. Preconstricted SW mesenteric arteries were more sensitive to acetylcholine (ACh) than SD ones. This difference was unaffected by L-NAME but was abolished by charybdotoxin and apamin. Exogenous superoxide dismutase (SOD) and catalase induced powerful relaxations in aortic rings, which were smaller in those from SW rats. In mesenteric and pulmonary arteries, however, they partially inhibited ACh-mediated relaxation, and enhanced PGF(2alpha)-mediated contraction, respectively. Our results suggest that feeding aging male rats a soy-rich diet results in improved agonist-mediated EDHF production and a generalized reduction in contractile force, which is partly due to elevated basal NO. Our data also suggest a prorelaxant role for endogenous H(2)O(2) in small arteries, which is modulated by a soy diet.     

The role of adrenergic stimulation of the arteries in their developing rhythmic contractions in arterial normo- and hypertension in rats]

In anaesthetised Wistar and SHR rats, rhythmic contractile responses of mesenteric arteries to noradrenaline as well as sympathetic nerve stimulation, were studied. Under equal experimental conditions, different parameters of vasomotion in normo- and hypertensive rats were revealed.