Role of endothelium on the effects of neuropeptide Y in mesenteric resistance arteries of spontaneously hypertensive and Wistar-Kyoto normotensive rats

The role of the endothelium in the effects of neuropeptide Y (NPY) and norepinephrine was investigated in mesenteric resistance arteries of the spontaneously hypertensive rat (SHR) and of the normotensive Wistar-Kyoto rat (WKY). Endothelium-dependent relaxation to acetylcholine (1 microM) was reduced in arteries of SHR compared with WKY. In the presence of the endothelium, the vessels of the two strains responded similarly to norepinephrine and NPY (100 nM) produced only a slight contraction. After removal of the endothelium, the response to norepinephrine was greater in WKY than in SHR. Furthermore, endothelium denudation enhanced markedly contraction elicited by NPY in WKY (up to 40% of the maximal effect of norepinephrine), but not in SHR. NPY potentiated the contractile response to low concentrations of norepinephrine (less than 300 nM) in both strains regardless whether the endothelium was intact or not. These results indicate that the contractile responses to NPY and to norepinephrine are inhibited by the endothelium in vessels of WKY, but not in those of the SHR. Furthermore, the potentiating effect of NPY occurs via an endothelium-independent mechanism in mesenteric arteries of both SHR and WKY. It is proposed that the differential responses between the two strains are related to abnormal function of the endothelium and to decreased responsiveness of smooth muscle cells in mesenteric resistance arteries of SHR compared to WKY.     

Pharmacodynamics and pharmacokinetics of intravenously administered morphine in spontaneously hypertensive and normotensive Wistar-Kyoto rats.

The analgesic and hyperthermic effects of i.v. administered morphine were determined in age-matched male spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats. Two doses of morphine (5 and 10 mg/kg) were used. In the doses used, morphine produced analgesia in WKY rats as measured by the tail-flick test and expressed as area under the time-response curve. The intensity and duration of the analgesic area under the time-response curve was significantly greater in SHR rats in comparison to WKY rats. For example, whereas the effect of a 10-mg/kg dose lasted for 4 hr in WKY rats; in SHR rats the effect lasted for 10 hr. Similarly, the intensity and duration of morphine-induced hyperthermic response was greater in SHR rats in comparison to WKY rats. In order to determine if the differences in responses to morphine in SHR and WKY were related to its kinetics, the pharmacokinetic parameters of morphine in serum were determined. The area under the serum morphine concentration-time curve, serum levels of morphine extrapolated to zero time, T1/2, apparent volume of distribution at steady state, terminal elimination rate constant and total body clearance values for morphine in SHR and WKY rats did not differ. Previous studies from this laboratory indicate that the density of mu opiate receptors labeled with [3H]D-Ala2.MePhe4,Gly-ol5-enkephalin and [3H]naltrexone and of kappa-opiate receptors labeled with [3H]ethylketocyclazocine in the brain of SHR rats is higher than in WKY rats.(ABSTRACT TRUNCATED AT 250 WORDS)     

Radiotelemetric evaluation of hemodynamic effects of long-term ethanol in spontaneously hypertensive and Wistar-Kyoto rats

This study determined the hemodynamic effects of chronic ethanol in telemetered freely moving age-matched spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats. Changes in blood pressure (BP), heart rate (HR), and plasma norepinephrine (as index of sympathetic activity) were evaluated in pair-fed rats receiving liquid diet with or without ethanol (5%, w/v) for 12 weeks. The SHRs exhibited higher baseline BP and lower HR compared with WKY rats. When normalized for body weight, daily ethanol intake was higher in SHRs compared with WKY rats. However, blood ethanol concentration was similar except for a higher level in SHRs at weeks 7 through 9. Ethanol had no effect on BP in WKY rats but caused decreases in BP in SHRs that reached a maximum (approximately 30 mm Hg) at week 5 and remained thereafter. Ethanol also caused reductions in the BP variability and the circadian fluctuations in BP in SHRs but not in WKY rats. Plasma norepinephrine levels were elevated by ethanol in WKY rats, but not in SHRs. The HR was not affected by ethanol in SHRs and showed increases in WKY rats. These findings suggest that chronic ethanol feeding differentially affects BP in SHRs (hypotension) and WKY rats (no effect). The lack of a hypotensive response to ethanol in WKY rats may relate, at least partly, to the associated sympathoexcitation. The present study used the telemetry technique for BP measurement, which eliminates the confounding and stressful effects of other conventional techniques.     

Sympatho-inhibitory actions of irbesartan in pithed spontaneously hypertensive and Wistar-Kyoto rats

Angiotensin II (Ang II) can enhance sympathetic neurotransmission by acting on (AT1) receptors that are located on sympathetic nerve terminals. We investigated presynaptic blockade by the selective AT1-receptor antagonist irbesartan in pithed spontaneously hypertensive rats and normotensive Wistar-Kyoto rats (WKY). We compared the presynaptic inhibitory dose with that required for the blockade of AT1-receptors on vascular smooth muscle in both strains. To investigate blockade of presynaptic AT1-receptors, we studied the effect of irbesartan on the sequelae of electric stimulation of the thoraco-lumbar sympathetic outflow (0.25-8 Hz). To study the interaction between postsynaptic AT1-blockers and alpha-adrenoceptors, the effects of irbesartan on pressor responses to exogenous noradrenaline (NA) were established. Additionally, we studied the effect of irbesartan on dose-response curves for the vasoconstriction induced by exogenous Ang II. Pressor responses to electrical stimulation of thoracolumbar sympathetic neurones, to exogenous Ang II, as well as to (NA) were enhanced in spontaneously hypertensive rats (SHR) compared with WKY. The stimulation-induced rise in DBP could be dose-dependently reduced by irbesartan (0.3-10 mg/kg) in both SHR and WKY. The pIC50 values (doses which suppress the rise in DBP by 50% compared with control) were 5.60 +/- 0.09 and 5.72 +/- 0.08 for SHR and WKY, respectively (P > 0.05). In SHR, no effect of irbesartan (3 mg/kg) on pressor responses to exogenous NA was observed. In contrast, in WKY, irbesartan (3 mg/kg) caused a rightward shift of the dose-response curve to exogenous NA. Irbesartan (0.3-3 mg/kg) caused a depression of E(max) values and a rightward shift of the dose-response curves to exogenous Ang II in a similar fashion in both SHR and WKY. From these results we conclude that both in SHR and in WKY, Ang II exerts a facilitatory effect on sympathetic neurotransmission, which is mediated by prejunctional AT1-receptors in both strains. Irbesartan displays comparable sympatho-inhibitory potency in the normotensive and hypertensive pithed rat preparations. A facilitatory effect via postsynaptically located AT1-receptors on alpha-adrenoceptor-mediated responses exists in WKY, but not in SHR. In both strains the required dose to inhibit presynaptic effects is somewhat higher than the dose required to inhibit postsynaptic effects. No differences, therefore, seem to exist between the two strains regarding the affinity of irbesartan for pre- and postjunctional AT1-receptors, respectively.     

Endothelin binding in brain of normotensive and spontaneously hypertensive rats.

The endothelins (ETs) are a recently discovered family of peptides which appear to be involved in hemodynamic regulation; they have potent vasoconstrictor properties and dose-related effects on blood pressure when administered peripherally. Little is known about the role of ET in the brain. The purpose of this study was to characterize the binding properties of various ETs in the brain of normotensive (Wistar-Kyoto) and hypertensive (spontaneously hypertensive) rats. [125I]ET 1 was prepared using the enzymobead lactoperoxidase method and purified by high-pressure liquid chromatography. Membrane fractions were prepared from homogenates of various brain regions. A differential distribution of ET binding was found among the 14 brain regions studied. The cerebellum, brainstem and area postrema/nucleus tractus solitarius had the highest binding, whereas the cortex, pituitary and septum had the least binding. Competition experiments performed with hypothalamus, brainstem and cerebellum demonstrated different Ki values for the ET studied. ET 2 had the highest affinity with a Ki of 4 x 10(-1) M, whereas the ET analog, Ala3,11-ET 1, had the lowest affinity with a Ki of 3 x 10(-10) M. Saturation experiments indicated a single class of high-affinity receptors in cerebellar (Kd = 2.5 x 10(-11) M, maximal binding Bmax = 1.25 x 10(-12) mol/mg) and hypothalamic membranes (Kd = 1.9 x 10(-11) M, Bmax = 0.93 x 10(-12) mol/mg). No differences in Kd or Bmax were detected between Wistar-Kyoto and spontaneously hypertensive rats hypothalamic and cerebellar tissues. The results of this study suggest a role for ET in the brain, but revealed no differences between normotensive and hypertensive strains.     

Time course of the distribution of morphine in brain regions and spinal cord after intravenous injection to spontaneously hypertensive and normotensive Wistar-Kyoto rats.

Previous studies from this laboratory have demonstrated that the analgesic and hyperthermic effects of morphine were found to be greater in spontaneously hypertensive (SHR) rats than in normotensive Wistar-Kyoto (WKY) rats. The enhanced response to morphine could not be explained on the basis of any of the pharmacokinetic parameters of morphine in the serum. In order to determine the possible contribution of altered distribution of morphine in the central nervous system in the differences in the pharmacological response to morphine in the two strains, the time course of the distribution of morphine was determined in brain regions and spinal cord after its i.v. administration. SHR and WKY rats were injected with morphine (10 mg/kg). At various times (5, 30, 60, 120 and 360 min) after the injection of morphine, brain regions (hypothalamus, cortex, hippocampus, midbrain, pons and medulla, striatum and amygdala) and spinal cord were collected. The level of morphine in the tissues was determined by using a highly sensitive and specific radioimmunoassay method. Five minutes after morphine injection, the concentration of morphine was the highest in the spinal cord. Among the brain regions, the highest concentration of morphine was in the hypothalamus and the lowest in the amygdala. In all the brain regions and spinal cord, the concentration of morphine was significantly higher in the SHR than in the WKY rats. Similar effects were observed at 30, 60 and 120 min after morphine injection. At 360 min, the hypothalamus, cortex and spinal cord of the SHR rats had higher concentrations of morphine than the WKY rats, but the other regions did not show differences in the morphine levels.(ABSTRACT TRUNCATED AT 250 WORDS)     

Leukotriene D4: cardiovascular and sympathetic effects in spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats

Leukotriene D4 (1--20 micrograms/kg i.a.) administered to conscious spontaneously hypertensive rats (SHR) and WKY rats caused acute elevation of blood pressure in both groups, but only in SHR a prolonged hypotensive period followed the hypertensive event. SHR rats had tachycardia during the hypertensive phase and relative bradycardia during the hypotensive phase which was more pronounced and prolonged than in WKY rats. In SHR rats only, plasma epinephrine and norepinephrine were elevated (6- and 3-fold, respectively) at the peak of the hypertensive period. Pretreatment of SHR rats with indomethacin (5 mg/kg) potentiated the LTD4-induced pressor response and shortened the hypotensive-bradycardic effect of LTD4. This same biphasic, dose-dependent response to LTD4 (1--20 micrograms/kg i.v.) was present in pithed SHR rats. Therefore, a direct action of LTD4 on vascular smooth muscle and heart is suggested. In all WKY rats and some SHR rats, a bradycardic effect of LTD4 resulted from sinus bradycardia, whereas in pithed SHR rats impaired conduction varying from transient second degree atrioventricular block to complete heart block was observed. Electrocardiographic signs of ischemia were seen only in LTD4-injected, pithed SHR rats. These results suggest fundamental differences between SHR and WKY rats in regard to their sensitivity to lipoxygenase products.     

Influence of age on glomerular binding of angiotensin II in normotensive and spontaneously hypertensive rats

1. Glomerular angiotensin II (ANG II) binding has been studied in normotensive (NTR) and spontaneously hypertensive (SHR) rats at 5, 10, 15 and 20 weeks of age. 2. Binding of 125I-labelled ANG II by glomeruli from NTR and SHR was similar at 5 and 10 weeks of age, with 5 week values of 426.4 (range 384-469) and 400.2 +/- 245 fmol/mg of protein; however, at 15 and 20 weeks ANG II binding by SHR glomeruli was significantly greater than by NTR, with 20 week values of 614.7 +/- 245 and 308.3 +/- 31.8 fmol/mg of protein, respectively (P less than 0.01). 3. The ANG II binding affinity constant (Ka) of glomeruli from NTR and SHR was comparable at 5, 10 and 15 weeks of age, with values of 1.5 (range 1.1-1.9) and 1.08 +/- 0.35 nmol/l, respectively, at 5 weeks; whereas at 20 weeks the Ka for SHR glomeruli was significantly greater than for NTR, with values of 1.85 +/- 0.45 and 0.66 +/- 0.22 nmol/l, respectively (P less than 0.001). 4. Age-related changes in glomerular binding of ANG II in SHR were not found to be related to changes in either plasma renin activity or systolic blood pressure.     

Effect of angiotensin-converting enzyme inhibitors on glomerular eicosanoid production in normotensive and spontaneously hypertensive rats.

1. This study was designed to examine the production of certain eicosanoids (prostaglandin E2), prostacyclin (as 6-keto-prostaglandin F1 alpha) and thromboxane A2 (as thromboxane B2) by glomeruli isolated from normotensive Wistar-Kyoto and spontaneously hypertensive rats both before and after the administration of one of three angiotensin-converting enzyme inhibitors, captopril, enalapril or fosinopril, for 10 days. 2. Measurements of glomerular eicosanoid production were made under basal conditions and in the presence of excess exogenous arachidonic acid. 3. The production of prostaglandin E2, 6-keto-prostaglandin F1 alpha and thromboxane B2 was greater by glomeruli from untreated spontaneous hypertensive rats (prostaglandin E2 2.24 +/- 0.41, 6-keto-prostaglandin F1 alpha 1.20 +/- 0.13 and thromboxane B2 2.75 +/- 0.43 ng 10 min-1 mg-1 of protein) than by those from Wistar-Kyoto rats (prostaglandin E2 1.41 +/- 0.28, 6-keto-prostaglandin F1 alpha 0.98 +/- 0.11 and thromboxane B2 1.29 +/- 0.24 ng 10 min-1 mg-1 of protein) under basal conditions. However, these differences only achieved statistical significance for thromboxane B2 (P less than 0.01). Similar strain-related differences were noted in the presence of arachidonic acid. 4. The ratio of glomerular (prostaglandin E2 + prostacyclin)/thromboxane A2 production was significantly lower in spontaneously hypertensive rats than in their normotensive counterparts under basal conditions with values of 1.3 +/- 0.18 and 2.2 +/- 0.20, respectively (P less than 0.01). 5. Angiotensin-converting enzyme inhibitors induced significant changes in the glomerular production of some eicosanoids, which differed both between strains and with the nature of the inhibitor.(ABSTRACT TRUNCATED AT 250 WORDS)     

Influence of dietary protein on glomerular angiotensin II-receptor binding in normotensive and spontaneously hypertensive rats.

1. The binding of angiotensin II to glomerular receptors was studied in spontaneously hypertensive and normotensive Wistar-Kyoto rats in response to 7, 16 and 32% isocaloric, isonatraemic protein diets. 2. Increased dietary protein elevated the systemic angiotensin II levels of both spontaneously hypertensive and Wistar-Kyoto rats [F0.05(2,26) = 4.758, P less than 0.05; n = 36], and this was not associated with changes in either systemic blood pressure or cortical renin activity. 3. Furthermore, no significant changes in the affinity or density of angiotensin II receptors were associated with changes of dietary protein intake in either strain. 4. These results indicate a dissociation between the system renin-angiotensin system and the tissue renin-angiotensin system in response to protein intake.     

Catecholamine turnover in normotensive and hypertensive man: effects of antiadrenergic drugs

Intravenous administration of tritium-labeled 3,4-dihydroxyphenylalanine (dopa) to human subjects resulted in the labeling of endogenous catecholamines and vanillylmandelic acid (VMA). Determination of the changes in specific activity of these compounds with time in fractional collections of urine and in cardiac biopsies from patients undergoing corrective cardiac surgery permitted estimation of apparent turnover rates. The average half-time of the exponential decline in specific activity of labeled urinary norepinephrine was about 8 hr and that of VMA was 11-16 hr in five normal subjects. No significant differences from normal were observed in eight patients with essential hypertension. The average half-life of norepinephrine was only 5 hr in cardiac patients undergoing surgery, and the levels and rate of decline of cardiac norepinephrine specific activity correlated well with the exponential phase of the urinary disappearance curve. There were significant effects of treatment with alpha-methyltyrosine, reserpine, and pargyline hydrochloride on the labeling and apparent turnover rates of norepinephrine and VMA; the effects noted were consistent with known actions of these three drugs. It is suggested that the technique used is a suitable means of assessing “over-all” catecholamine metabolism in man, particulary if combined with quantitative assay of urinary catecholamine metabolites.     

Thyroid function and blood pressure in two new strains of spontaneously hypertensive and normotensive rats

1. The influence of thryoid function on the development of hypertension was studied in strains of spontaneously hypertensive (SH) and normotensive rats. 2. Surgical thyroidectomy decreased systolic blood pressure more markedly in SH rats than in normotensive rats. The effects of oral administration of 5 and 100 micrograms of thyroxine 24 h-1 100 g-1 were studied in the thyroidectomized animals. In the two strains the blood pressure returned to control levels only after administration of the larger dose. 3. The evolution of body weight, total plasma tri-iodothyronine (T3) and tetraiodothyronine (T4) concentrations were followed as a function of age in SH rats and normotensive rats from 5 to 21 weeks. At each age, SH rats showed significantly larger body weight and decreased T4 concentrations. Plasma T3 in SH rats was lower than in normotensive rats until 15 weeks of age, after which the difference was not significant. At 11 weeks, plasms free T3 and T4 concentrations were slightly lower in SH rats than in normotensive rats. 4. The more marked hypotensive effects of surgical thyroidectomy in SH rats cannot be related to increased thyroid function.     

Mechanisms of altered sensitivity to endothelin-1 between aortic smooth muscles of spontaneously hypertensive and Wistar-Kyoto rats

Endothelin-1 (ET-1) caused a dose-dependent vasoconstriction in rat aortic strips in vitro. The sensitivity to ET-1 was significantly higher in 12-week-old spontaneously hypertensive rats (SHR) than in age-matched Wistar-Kyoto (WKY) rats. In contrast, the sensitivity was not different between SHR and WKY rats at 6 weeks of age, which was close to that of 12-week-old SHR. Receptor binding study in microsomal preparations of the aortas with [125I]ET-1 showed that maximum binding value for ET-1 receptor in 12-week-old SHR was only 1.5-fold greater than that in WKY rats and that there was no significant difference in the Kd values. K(+)-depolarization induced vasoconstrictive responses that were also augmented in 12-week-old SHR. Resting membrane potential of the aorta was significantly depolarized in tissues from 12-week-old SHR compared with age-matched WKY rats. The resting membrane potentials were similar in the aorta from 6-week-old SHR and WKY rats, and were between those of 12-week-old SHR and WKY rats. When the aortic strips from 12-week-old WKY rats were partially depolarized in high K(+)-solution or in the presence of ouabain (0.1 mM), the vasoconstrictor effect of ET-1 became similar to that on the strips from SHR in a normal solution. These results suggest that, although age-dependent changes appear to be complicated, the lower resting membrane potential may account considerably for the larger sensitivity to ET-1 in the aorta from 12-week-old SHR than that from age-matched WKY rats.     

Differences in glomerular binding and response to angiotensin II between normotensive and spontaneously hypertensive rats

1. Angiotensin II (ANG II) binding and the physiological response to exogenous ANG II have been studied in isolated glomerular preparations from normotensive (NTR) and spontaneously hypertensive (SHR) rats. 2. The binding of 125I-labelled ANG II by glomeruli from SHR was significantly greater than that by glomeruli from NTR, whereas the binding affinity constant (Ka) showed that the SHR ANG II glomerular receptor had a lower affinity for the hormone than the NTR glomerular receptor. 3. Glomeruli from SHR were significantly less responsive to exogenous ANG II than those from NTR. 4. Sodium loading resulted in a significant increase in ANG II binding by glomeruli from NTR, whereas a decrease in binding occurred in glomeruli from SHR. 5. Although a high sodium intake caused a reduction in the response of glomeruli from both NTR and SHR to exogenous ANG II, these changes were not statistically significant. In NTR this was associated with a decrease in the concentration of agonist required to cause half-maximal response (EC50), whereas an increase in EC50 was shown by glomeruli from SHR.     

Influence of experimental reduction of media/lumen ratio on arterial myogenic properties of spontaneously hypertensive and Wistar-Kyoto rats

In the present study, myogenic properties of femoral arteries from control hindlimbs and those distal to external iliac artery partial ligation of spontaneously hypertensive rats (SHRs) and normotensive Wistar-Kyoto (WKY) rats were assessed. Arterial pressure was reduced distal to the ligature in both strains. Media thickness/lumen diameter (M/L) ratios of control (unligatured) SHRs were greater than in unligatured WKY rats and were reduced in arteries distal to the ligature (ligatured) within each strain. In none of the comparisons was a greater M/L ratio associated with greater maximal myogenic contractions, but increased M/L ratios were associated with a shift of myogenic activity to a higher pressure range in all comparisons. SHR ligatured arteries produced greater pressure-dependent contractile responses than WKY rat unligatured arteries, although arterial structures were not significantly different. Wall stress was similar in all arteries within the 60-120 mmHg pressure range with myogenic tone in spite of large differences in arterial structure. The utilization of arteries with experimentally altered structure provides further evidence that increased M/L ratios are not associated with greater peak pressure-dependent contractile responses and that arterial wall stress is maintained within a narrow range through an interaction between arterial wall geometry and smooth muscle contractile function.     

Relationship between noradrenaline and nonlinear indexes of blood pressure dynamics in normotensive and spontaneously hypertensive rats

Recent studies in normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats show that some nonlinear indexes derived from the recurrence plot method may be better markers of sympathetic activity than the spectral powers of blood pressure (BP). We herein investigated the relationships between nonlinear indexes and plasma noradrenaline concentration in conscious WKY rats and SHRs. Blood pressure was recorded for 30 min after intravenous injection of saline (0.9% NaCl, 100 microL/kg), hexamethonium (20 mg/kg), atropine (0.5 mg/kg), atenolol (1 mg/kg) or prazosin (1 mg/kg). Spectral power in the low-frequency (LF) band and the nonlinear index (L(max)), calculated on diastolic (DBP) and systolic blood pressures (SBP), were used to analyse the BP signal. Noradrenaline concentration was determined by radioenzymatic technique. A robust stepwise regression analysis - using noradrenaline concentration as dependent variable, and LF, L(max) and treatment, as independent variables -shows that treatment is the main variable explaining the variance of noradrenaline level in WKY rats, excluding the use of the pooled data to explore the relationship between noradrenaline concentration and LF or L(max). In contrast, in SHRs, treatment has no effect on the variance of noradrenaline concentration and the pooled data were then used. In this group, no correlation was observed between noradrenaline concentration and LF. In contrast, very high positive correlation was observed between noradrenaline level and L(max)-DBP (r = 0.59; P = 0.0005) or L(max)-SBP (r = 0.53; P < 0.002). The results strengthen our previous suggestion that nonlinear indexes may be better tools than spectral powers to investigate the sympathetic nervous system.     

硝苯地平对自发性高血压大鼠血管内皮细胞的保护作用

背景研究表明,硝苯地平能够改善血管内皮细胞功能,而对于其扩张血管的机制,目前仍在进一步的研究中. 目的观察硝苯地平控释剂对自发性高血压大鼠(SHR)一氧化氮(NO)及诱导性一氧化氮合酶(iNOS)的影响.设计以实验动物为研究对象的观察对比研究.单位一所医学院的动物实验中心.材料本实验于2002-04/2002-05在山东大学医学院动物实验中心完成.实验动物为近交SHR大鼠21只,体质量(300±20)g,由山东大学医学院实验动物中心提供,清洁级.随机分为3组,即对照组、正常剂量组、低剂量组,每组7只. 方法对照组、正常剂量组和低剂量组分别灌胃生理盐水10 mL/kg、硝苯地平控释剂(拜新同)溶液(0.3 g/L)10 mL/kg和3 mL/kg,1次/d,连续15 d.末次给药后摘眼球取血并取大鼠心、肺分别测定血清NO和iNOS的含量.主要观察指标各组大鼠的NO含量、iNOS活性比较.结果灌胃15 d后,正常剂量组的NO含量与对照组、低剂量组比较,差异均有显著性意义(P<0.01);正常剂量组心、肺组织块中iNOS活性降低,与对照组和低剂量组比较差异均有显著性意义(P<0.01,P<0.05).结论硝苯地平可在降低血压的同时,提高血清NO的含量,并且能对抗血压增高所造成的iNOS的活性增强(或二者互为因果).     

Voluntary physical exercise-induced vascular effects in spontaneously hypertensive rats

Forced training has been shown to have beneficial vascular effects in various animal exercise models. In the present study, we explored possible physiological and molecular effects of voluntary physical exercise on various vascular beds. SHR (spontaneously hypertensive rats) performed voluntary exercise for 5 weeks in a computerized wheel cage facility. Ex vivo myograph studies revealed an increased sensitivity of the ACh (acetylcholine)-mediated vasodilation in resistance arteries of the exercised animals (ED50=15.0+/-3.5 nmol/l) compared with the controls (ED50=37.0+/-8.8 nmol/l; P=0.05). The exercise/control difference was abolished after scavenging reactive oxygen radicals. In conduit arteries, ACh induced a similar vasodilatory response in both groups. The in vivo aortic wall stiffness, assessed by means of Doppler tissue echography, was significantly lower in the exercising animals than in controls. This was demonstrated by significantly increased peak systolic aortic wall velocity (P=0.03) and the velocity time integral (P=0.01) in exercising animals compared with controls. The relative gene expression of eNOS (endothelial nitric oxide synthase) was similar in both groups of animals, whereas Cu/ZnSOD (copper/zinc superoxide dismutase) gene expression was significantly increased (+111%; P=0.0007) in the exercising animal compared with controls. In conclusion, voluntary physical exercise differentially improves vascular function in various vascular beds. Increased vascular compliance and antioxidative capacity may contribute to the atheroprotective effects associated with physical exercise in conduit vessels.     

Vasopressin-mediated contractions in mesenteric arteries from spontaneously hypertensive rats: differences in response compared with Wistar-Kyoto animals

1. The sensitivity of mesenteric resistance arterioles to [arginine]vasopressin (AVP) was investigated in spontaneously hypertensive rats (SHR) and control Wistar-Kyoto rats (WKY). No difference in pAVP (-log dose of AVP producing 50% of the maximum response) was observed [SHR 0.21 +/- 0.03 m-units/ml (n = 10) vs WKY 0.15 +/- 0.06 m-units/ml (n = 9)], although SHR vessels exhibited greater absolute tension development. 2. Both strains of rat displayed tachyphylaxis to repeated stimulation with AVP, and oscillatory tension changes were observed in all vessels from SHR and rarely in WKY vessels at activating concentrations of AVP. 3. AVP did not elicit a contractile response after noradrenaline-induced calcium depletion. 4. After vessels were depleted of calcium by using a combination of calcium-free media and noradrenaline stimulation, restoration of calcium in the presence of AVP elicited a greater contractile response in SHR vessels. 5. The results therefore provide evidence for an increased calcium response to AVP in SHR resistance vessels, although this was only demonstrable by calcium recovery experiments.