抗氧化剂PZ51对SHRsp血管内皮细胞作用

目的　研究抗氧化剂PZ5 1对SHRsp高血压发展的慢性过程中内皮细胞的作用及可能的机制。方法　 2 2只 8周龄SHRsp大鼠随机分为PZ5 1组和对照组 ,灌胃治疗 6周。用分光光度计测血浆NO、MDA浓度 ;免疫组化检测颈动脉eNOS蛋白表达 ;电镜扫描颈动脉内皮细胞。结果　PZ5 1组较对照组血浆MDA浓度显著降低 (7.88± 1 0 6vs 10 88± 1.73) μmol/L ,P <0 0 0 1、NO浓度显著升高 (4 0 0 2± 9.74vs 2 2 .2 2± 10 0 5 ) μmol/L ,P <0 0 0 1;颈动脉内皮eNOS蛋白表达显著增加 (8.2 5± 2 .36vs 4 .4 6± 3.14 ,P =0 0 2 6 ) ;电镜检查示PZ5 1组血管内皮细胞病变较对照组轻。结论PZ5 1对SHRsp血管内皮有保护作用 ,可能与其升高内皮细胞eNOS表达、增加血浆NO水平、抑制脂质过氧化有关。     

血管紧张素1型受体拮抗剂对卒中易感型自发性高血压大鼠脑的保护作用

目的　研究长期口服血管紧张素 1受体拮抗剂氯沙坦对卒中易感型自发性高血压大鼠(SHRsp)的脑保护机制。　 方法　 6周龄雄性SHRsp 2 6只 ,随机分为生理盐水、小剂量氯沙坦 (10mg·kg 1·d 1)和大剂量氯沙坦 (30mg·kg 1·d 1) 3组 ,以 8只 6周龄雄性京都Wistar大鼠 (WKY)作为正常对照 ,记录体重、血压和脑卒中临床表现评分 ,18周后断头处死 ,光镜和电镜观察脑组织结构 ;TUNEL法检测神经细胞凋亡。　结果　 18周后SHRsp大剂量用药组血压 (16 9 4± 10 1)mmHg明显低于未用药组 (2 2 5 5± 6 8)mmHg ,(P <0 0 5 ) ,小剂量用药组血压 (2 16 7± 8 3)mmHg ,与对照组比较改变不明显 (P >0 0 5 ) ;SHRsp未用药组脑卒中评分 (3 5± 0 6 )显著高于小剂量用药组 (0 7± 1 1)和大剂量用药组 (0 4± 0 7) ,(P <0 0 5 ) ;上述 3组神经元凋亡率分别为 :5 2 0± 16 7、14 0±4 4、13 9± 4 3,SHRsp未用药组神经元凋亡率高于小剂量和大剂量用药组 ,差异有显著性(P <0 0 5 )。　结论　氯沙坦能降低SHRsp脑卒中发生率、减少SHRsp神经细胞凋亡 ,此作用与血压无关。     

膳食添加剂对卒中易感型自发性高血压大鼠的影响

卒中易感型自发性高血压大鼠(SHRsp)具有较高的卒中发生率.研究结果表明,合理的营养膳食可改善SHRsp高血压卒中的发病率.     

鱼油对卒中易感型自发性高血压大鼠高血压发展过程的影响

观察饮食鱼油或花生油对卒中易感型自发性高血压大鼠（ＳＨＲｓｐ）血压、血脂和心、脑、肾结构的影响。大鼠喂养标准实验室饮食（对照组）或含１２％花生油（花生油组）或１２％鱼油（鱼油组）的饮食１７周。结果表明饮食鱼油能够缓解ＳＨＲｓｐ高血压的发展；降低总胆固醇（ＴＣ）和甘油三酯（ＴＧ）水平，显著升高高密度脂蛋白胆固醇（ＨＤＬｃ）水平；饮食鱼油能够减缓左室肥厚的发展，减轻靶器官小血管的病理改变，对高血压靶器官具有明显的保护作用。与之相反，饮食花生油对ＳＨＲｓｐ的血压、高密度脂蛋白胆固醇、甘油三酯无影响，饮食花生油升高总胆固醇水平，加剧高血压靶器官脑、心、肾的病变。     

缬沙坦对卒中易感型自发性高血压大鼠脑血管结构的影响

目的 :研究长期口服血管紧张素Ⅱ 1型受体拮抗剂———缬沙坦对卒中易感型自发性高血压大鼠(SHRsp)脑血管形态结构的影响 ,探讨其可能的脑保护机制。 方法 :6周龄雄性SHRsp2 6只随机分为 3组 ,以 8只 6周龄雄性正常血压大鼠 (WKY)作为正常对照 ,记录血压和脑卒中临床表现评分 ,18周后断头处死 ,镜下观察脑血管结构。结果 :① 18周后SHRsp组和小剂量缬沙坦 (2 0mg·kg-1·d-1)用药组 (SHRSP加V2 0 组 )血压均分别高于WKY组和大剂量缬沙坦 (4 0mg·kg-1·d-1)用药组 (SHRSP加V40 组 ) ,P <0 .0 5。②SHRsp组脑卒中临床表现评分明显高于SHRSP加V2 0 组和SHRSP加V40 组 ,SHRSP组死亡率为 33.33% ,SHRSP加V2 0 组和SHRSP加V40 组均无死亡。③SHRsp组脑动脉中膜厚度 /管腔半径的比值明显高于WKY组、SHRSP加V2 0 组和SHRSP加V40 组 ,P<0 .0 5 ;而后三者之间脑动脉中膜厚度 /管腔半径的比值差异均无显著性意义 (P >0 .0 5 )。结论 :缬沙坦可通过降低SHRsp脑动脉中膜厚度 /管腔半径的比值、干预血管重构发挥脑血管保护作用 ,此作用与血压无关。     

脑有对卒中型自发性高血压大鼠脑卒中的治疗作用

为探讨脑复清对脑卒中型自发性高血压大鼠（ＳＨＲｓｐ）脑卒中的治疗作用，给ＳＨＲｓｐ饮１％ＮａＣｌ盐水，大鼠脑卒中发生后分别用脑复清０．５ｇ／ｋｇ．ｄ、１．０ｇ／ｋｇ．ｄ、２．０ｇ／ｋｇ．ｄ、２．０ｇ／ｋｇ．ｄ治疗，并与维脑路通１．０ｇ／ｋｇ．ｄ、２．０ｇ／ｋｇ．ｄ及溶媒剂作比较，治疗１４天。脑复清３组及维脑路通２组大鼠脑中卒临床症状评分（１．３－１．６分）均显著好于溶媒对照组（３．３，均Ｐ〈０．０     

卒中易感型自发性高血压大鼠繁育能力及脑卒中特性的研究

目的　研究卒中易感型自发性高血压大鼠 (SHRsp)的繁育能力及脑卒中的特性。材料和方法　采用兄妹交配方法 ,观察记录雌性SHRsp两年的受孕率及产仔数 ,分别于 12、16、2 0周龄时测量种鼠的收缩压和心率。另取 48只 8周龄SHRsp在 1%NaCl盐水负荷下 ,观察 12周 ,取大鼠脑组织经处理后 ,在光镜下观察脑卒中发生率。结果　第一年度生产 2代 ,平均SHRsp雌鼠受孕率及孕鼠平均产仔数分别为 10 0 %与 10 3只 ,SHRsp受孕率高于同期WKY( 90 0 % ) (P =0 0 77) ;SHRsp平均产仔数 ( 10 3只 )高于WKY( 6 5) (P <0 0 0 1)。第二年度SHRsp与WKY平均受孕率及孕鼠平均产仔数与第一年度近似。SHRsp血压随周龄增加而升高 ,12周龄雄鼠收缩压 191 6mmHg～ 2 2 3 8mmHg ,雌鼠为 174 2mmHg～ 196 3mmHg ,2 0周龄雄鼠收缩压达 2 3 2 0mmHg～ 2 42 6mmHg。雄鼠心率 3 88～ 42 8次 /分 ,雌鼠为 3 73～ 417次 /分。SHRsp脑卒中病理检出率 81 3 %。 结论　SHRsp繁育能力与WKY相似 ;以血压和脑组织病理检查表明 ,保持了SHRsp高血压和脑卒中的特性     

卒中易感型自发性高血压大鼠繁育能力及脑卒中特性的研究

目的研究卒中易感型自发性高血压大鼠(SHRsp)的繁育能力及脑卒中的特性. 材料和方法采用兄妹交配方法,观察记录雌性SHRsp两年的受孕率及产仔数,分别于12、16、20周龄时测量种鼠的收缩压和心率.另取48只8周龄SHRsp在1% NaCl盐水负荷下,观察12周,取大鼠脑组织经处理后,在光镜下观察脑卒中发生率.结果第一年度生产2代,平均SHRsp雌鼠受孕率及孕鼠平均产仔数分别为100%与10.3只,SHRsp受孕率高于同期WKY(90.0%)(P=0.077); SHRsp平均产仔数(10.3只)高于WKY(6.5)(P<0.001).第二年度SHRsp与WKY平均受孕率及孕鼠平均产仔数与第一年度近似.SHRsp血压随周龄增加而升高,12周龄雄鼠收缩压191.6 mmHg～223.8 mmHg,雌鼠为174.2 mmHg～196.3 mmHg,20周龄雄鼠收缩压达232.0 mmHg～242.6 mmHg.雄鼠心率388～428次/分,雌鼠为373～417次/分.SHRsp脑卒中病理检出率81.3%.结论 SHRsp繁育能力与WKY相似;以血压和脑组织病理检查表明,保持了SHRsp高血压和脑卒中的特性.     

普伐他汀对脑卒中易感型自发性高血压大鼠脑损害及内皮细胞功能的影响

目的　了解普伐他汀对脑卒中易感型自发性高血压大鼠 (SHRsp)的脑损害的预防作用 ,并探讨其机制。方法　 (1)整体动物实验 :将 2 2只 7周龄SHRsp随机分为普伐他汀 (2 0mg·kg- 1 ·d- 1 )治疗组和对照组 ,灌胃治疗 8周 ,离取各组大鼠脑组织和颈动脉 ,分别进行透射电镜和扫描电镜检查。还检查了血压、血脂和血液循环内皮细胞(CEC)计数。 (2 )内皮细胞培养部分 :胎儿脐静脉内皮细胞经 0、1、2、5、15 μmol L不同浓度的普伐他汀作用 72h后 ,收取培养液。用Griess法测定一氧化氮 (NO)代谢产物亚硝酸盐的浓度。结果　 (1)整体动物实验 :治疗 8周 ,治疗组血压、血脂与对照组比较无明显差异。但在电镜下已观察到 :对照组颈动脉内皮细胞出现肿胀和脱失现象 ;神经细胞出现核固缩、线粒体肿胀和内质网扩张等病理改变。而治疗组颈动脉内膜和神经细胞形态病理改变不明显。治疗组CEC计数较对照组低 2 2 % [治疗组 (19.11± 5 .0 6 )个 mm3;对照组 (2 4 .5 0± 4 .90 )个 mm3,P =0 .0 2 6 ]。 (2 )内皮细胞培养部分 :经 0 ,1、2、5、15 μmol L不同浓度的普伐他汀作用 72h后 ,培养液中NO亚硝酸盐代谢产物浓度分别为 6 .99,6 .88、7.85、10 .5 7和 8.0 5 μmol L。结论　普伐他汀能够预防SHRsp脑损害的发生。该作用?     

抗氧化剂对急性坏死性胰腺炎大鼠一氧化氮、丙二醛的影响

目的　探讨抗氧化剂N_乙酰半胱氨酸 (NAC)对急性坏死性胰腺炎 (ANP)大鼠胰腺组织一氧化氮 (NO)及丙二醛(MDA)的影响。方法　雄性SD大鼠 114只 ,随机分成正常对照组 (C组 ,n =3 0 )、急性胰腺炎组 (A组 ,n =42 )和NAC干预组 (N组 ,n= 42 )。A组分 2次腹腔内注射 8%L_精氨酸 (L_Arg) 1 2mg/g诱导ANP ;C组同法腹腔内注射等量生理盐水 ;N组先提前 1小时 (h)腹腔内注射 0 5mol/L的NAC 0 0 5mg/g ,然后同A组方法诱导ANP。在首次注射L_Arg后于 6h、12h、2 4h、3 6h、48h、72h分批处死大鼠 ,观察大鼠胰腺组织NO和MDA水平及胰腺病理变化。结果　N组各时点NO和MDA水平均较A组明显降低 (均P <0 0 1或P<0 0 5) ,N组 12h、2 4h、3 6h、48h、72h的胰腺病理改变较A组的明显减轻 (均P <0 0 1或P <0 0 5)。结论　NAC可降低胰腺组织NO、MAD水平 ,减轻了实验性ANP大鼠的胰腺损害 ,对胰腺组织有保护作用     

Protective effect of antioxidant ebselen (PZ51) on the cerebral cortex of stroke-prone spontaneously hypertensive rats.

An increase in reactive oxygen species has been shown to play a role in perpetuating hypertension and cerebral injury in stroke-prone spontaneously hypertensive rats (SHRsp). Lipid peroxidation in the cerebral cortex is much more intense in SHRsp after establishment of severe hypertension as compared to that in normotensive Wistar-Kyoto rats (WKY). Cortical neurons from SHRsp are more vulnerable to hypoxia and hyponutritional conditions. We sought to investigate whether long-term administration of seleno-glutathione peroxidase mimic ebselen (PZ51) would have a protective effect on cortical neurons in SHRsp, and, if so, the possible mechanisms of this effect. Twenty-two 8-week-old SHRsp were randomized into a PZ51 group and control group. Age-matched WKY were used as normal controls. We examined the levels of malonaldehyde (MDA) and nitric oxide (NO) in the cerebral cortex (CC) homogenate, detected the three isoforms of nitric oxide synthase (NOS) by Western blotting, and examined cortical neurons by transmission electron microscopy. The results showed that PZ51 treatment significantly decreased both MDA and NO in the CC, inhibited inducible nitric oxide synthase (iNOS) protein expression, and alleviated the damage to cortical neurons compared to the findings for the control group. In conclusion, the present study showed that PZ51 administration suppressed lipid peroxidation and inhibited iNOS protein expression in CC homogenate, and it was suggested that these mechanisms may play a role in the protective effects of PZ51 on cortical neurons of SHRsp.     

Effect of glutathione peroxidase mimic ebselen (PZ51) on endothelium and vascular structure of stroke-prone spontaneously hypertensive rats

BACKGROUND: To investigate whether extrinsic antioxidant seleno-glutathione peroxidase mimic ebselen (PZ51) can protect endothelium and vascular structure of stroke-prone spontaneously hypertensive rats (SHRsp) during the chronic process of hypertension. METHODS: Twenty-two 8-week-old SHRsp were randomized into a PZ51 group and a control group, and administered by gavage for 6 weeks. We examined the level of nitric oxide (NO) and malonaldehyde (MDA) in plasma. The intima-media thickness (IMT) of the common carotid artery (CCA) was measured by an image-analysis system. The endothelium of the CCA was observed by scanning electron microscopy. The eNOS protein of the major artery was assayed by immunohistochemistry and western blotting. RESULTS: Compared with the control group, PZ51 decreased plasma MDA (7.88+/-1.06 vs 10.88+/-1.73 nmol/l, p<0.001) and increased plasma NO (40.02+/-9.74 vs 22.22+/-10.05 micromol/l, p<0.001), increased eNOS protein expression (8.25+/-2.36 vs 4.46+/-3.14, p=0.026), decreased IMT (69.85+/-5.47 vs 76.60+/-6.53 microm, p<0.05) significantly and alleviated the damage to the endothelium of the CCA. CONCLUSION: Administration of PZ51 for 6 weeks can protect the endothelium and inhibit vascular remodeling, maybe due to its suppression of lipid peroxide formation and increase in eNOS protein expression.     

Myocardial beta-adrenergic receptors in the stroke-prone spontaneously hypertensive rat

In view of the severity of the hypertension in the stroke-prone spontaneously hypertensive rats (sp-SHR), myocardial beta-adrenergic receptors were investigated by the binding of (?)[³H]-dihydroalprenolol (DHA) to membranes from sp-SHR (9-week-old males, Okamoto-Aoki strain) and age-matched and sex-matched normotensive Wistar-Kyoto rats. Scatchard analysis showed no significant differences in binding parameters between sp-SHR and normal rats. Myocardial membranes from sp-SHR bound 31.8 ± 2.3 fmol DNA per mg protein with a dissociation constant of 3.8 ± 0.9 nm, whereas membranes from normal rats bound 33.4 ± 2.9 fmol DHA per mg protein with a dissociation constant of 3.9 ± 1.0 nm. However, mean arterial pressure and heart rate determined directly via aortic cannulae, while the rats were conscious and unrestrained, were significantly higher in sp-SHR. Plasma norepinephrine concentration was also significantly higher in sp-SHR. The finding that cardiac beta-adrenergic receptors are unchanged, despite evidence of increased sympathetic nerve activity, suggests that in the sp-SHR there may be a failure of catecholamine-induced “down regulation” of beta-adrenergic receptors. This defect could contribute to the increased cardiac drive in these animals and may thus explain the severity of the hypertension in this strain of spontaneously hypertensive rats.     

The effect of cicletanine on cerebrovascular injury in stroke-prone spontaneously hypertensive rats

The stroke-prone spontaneously hypertensive rat (SHR-SP) is one of the most suitable models for stroke study. The present trial work was undertaken so as to obtain further information concerning the action of a new furopyridine, cicletanine. Forty-six males--SHR-SP/Iffa Credo rats--aged 7 weeks, were divided into three groups. Group 1 was a control group, groups 2 and 3 were orally treated with cicletanine at 30 and 100 mg/kg. Their drinking water contained 1% NaCl. Systolic blood pressure, body weight, and survival were recorded. After 6 weeks, all the rats were sacrificed. Samples of heart, brain, and kidney were fixed for light and ultrastructural examination. We found that cicletanine treatment (30 and 100 mg/kg) had significantly inhibited the incidence of hypertensive cerebral damages as characterized by cerebral infarction and vascular alterations with fibrinoid necrosis. Compared with the control group, the rats treated with the cicletanine had a significantly increased survival rate (P less than .001); the cicletanine also had an important protective effect on tissue. Cicletanine administration prevented the development of hypertensive cerebral vascular damage, probably through direct action on the vascular walls.     

Genetic determinants of metabolic syndrome components in the stroke-prone spontaneously hypertensive rat

OBJECTIVE: The metabolic syndrome is a complex multifactorial disease, which results from interactions between genes on multiple chromosomes and environmental factors. Animal models may facilitate genetic analysis of complex phenotypes by allowing complete control of environmental conditions and the ability to produce designer strains. METHODS: Stroke-prone spontaneously hypertensive (SHRSP) and Wistar-Kyoto (WKY) rat strains were used to construct congenic (SP.WKYGla2a), consomic (SP.WKYGlaYw, WKY.SPGlaYs) and double-introgressed (SP.WKYGla2aYw) strains, which were characterized for metabolic syndrome phenotypes (systolic blood pressure, glucose tolerance and lipid profile) after feeding a 60% fructose diet for 14 days. RESULTS: The Y consomic strain (SP.WKYGlaYw) demonstrated that the WKY Y chromosome significantly lowered triglyceride levels (3.77 +/- 0.60 versus 9.09 +/- 1.47 mmol/l; P < 0.001) and improved glucose tolerance [area under the curve (AUC): 26.93 +/- 0.81 versus 31.47 +/- 0.89; P < 0.05] compared with SHRSP. The chromosome 2 congenic strain (SP.WKYGla2a) exhibited significantly improved glucose tolerance (AUC: 28.19 +/- 1.17 versus 31.47 +/- 0.89; P < 0.05) and lower systolic blood pressure (161.2 +/- 6.2 versus 179.7 +/- 3.9 mmHg; P < 0.05) compared with SHRSP. 2 x 2 factorial ANOVA identified a significant interaction for glucose metabolism (P = 0.004) in the double-introgressed strain (SP.WKYGla2aYw) between chromosome 2 and Y. CONCLUSIONS: These results identify novel interacting regions on chromosome 2 and the Y chromosome influencing a cluster of metabolic and cardiovascular phenotypes. Translation to clinical studies will facilitate genetic dissection of human metabolic syndrome.     

Dysregulation of cadherins in the intercalated disc of the spontaneously hypertensive stroke-prone rat

The structural integrity of cardiac cells is maintained by the Ca²⁺-dependent homophilic cell–cell adhesion of cadherins. N-cadherin is responsible for this adhesion under normal physiological conditions. The role of cadherins in adverse cardiac pathology is less clear. We studied the hearts of the stroke-prone spontaneously hypertensive (SHRSP) rat as a genetic model of cardiac hypertrophy and compared them to Wistar–Kyoto control animals. Western blotting of protein homogenates from 12-week old SHRSP animals indicated that similar levels of β, γ-, and α-catenin and T, N and R-cadherin were expressed in the control and SHRSP animals. However, dramatically higher levels of E-cadherin were detected in SHRSP animals compared to controls at 6, 12 and 18 weeks of age. This was confirmed by quantitative Taqman PCR and immunohistochemistry. E-cadherin was located at the intercalated disc of the myocytes in co-localisation with connexin 43. Adenoviral overexpression of E-cadherin in rat H9c2 cells and primary rabbit myocytes resulted in a significant reduction in myocyte cell diameter and breadth. E-cadherin overexpression resulted in re-localisation of β-catenin to the cell surface particularly to cell–cell junctions. Subsequent immunohistochemistry of the hearts of WKY and SHRSP animals also revealed increased levels of β-catenin in the intercalated disc in the SHRSP compared to WKY. Therefore, remodelling of the intercalated disc in the hearts of SHRSP animals may contribute to the altered function observed in these animals.     

Defective suppression of the aldosterone biosynthesis during stroke permissive diet in the stroke-prone phenotype of the spontaneously hypertensive rat

Previous studies have shown that short-term high salt intake unmasks blunted plasma aldosterone suppression in stroke-prone spontaneously hypertensive rats (SHRsp). The aim of this study was to evaluate the response of aldosterone biosynthesis and production to a sustained exposure to the stroke-permissive Japanese-style diet (JD) in young stroke-prone and stroke-resistant SHRs. For this purpose, 6-week old male rats from both strains were divided into 2 dietary groups and received regular diet (SHR = 37, SHRsp = 32) or the JD and 1% saline to drink (SHR = 34, SHRsp = 30) for 4 weeks. All measurements were carried out at the end of the dietary periods. After JD, plasma aldosterone levels were significantly decreased in SHR (from 357.8±57 to 163.3±31.5 pg/ml, p < 0.05) but markedly increased in SHRsp (from 442±56.5 to 739±125.7 pg/ml, p < 0.05). Consistently, the adrenal aldosterone synthase expression was reduced by JD in SHR (p < 0.05), whereas it was even slightly raised by JD in SHRsp so that, at the end of JD, aldosterone synthase mRNA was 5-fold higher in SHRsp than in SHR. Urinary sodium excretion (mEq/24h) achieved lower levels in SHRsp, so that fractional excretion of sodium was 80.2±9% in SHR and 40.3±8% in SHRsp (p < 0.05) in balance studies performed at the end of JD. These different responses of mineralocorticoid biosynthesis and urinary sodium excretion to JD were not accounted for by different adaptions of the renin-angiotensin and atrial natriuretic peptide systems, of serum potassium levels, or of adrenal 11β-hydroxylase expression in the two strains. Systolic blood pressure was comparable in both strains throughout the experiment. These results demonstrate enhanced aldosterone biosynthesis, associated with reduced urinary excretion of sodium in response to JD in SHRsp before the onset of stroke. This abnormality may play a role in the higher susceptibility of stroke of this model. Received: 1 March 1999, Returned for 1. revision: 22 March 1999, 1. Revision received: 7 June 1999, Returned for 2. revision: 28 June 1999, 2. Revision received: 4 August 1999, Returned for 3. revision: 10 September 1999, 3. Revision received: 28 October 1999, Accepted: 17 November 1999     

Vascular reactivity in the spontaneously hypertensive stroke-prone rat. Effect of antihypertensive treatment

This study investigated vascular responsiveness in stroke-prone spontaneously hypertensive rats (SHRSP) and the effect of antihypertensive treatment on this responsiveness. Weanling (4-week-old) male and female SHRSP and Wistar-Kyoto rats (WKY) received either the antihypertensive combination treatment of hydralazine plus hydrochlorothiazide in drinking water or tap water alone (controls) for 15 weeks. Whereas the antihypertensive combination prevented the development of hypertension in treated SHRSP (SHRSP-T), blood pressure remained unchanged in treated WKY (WKY-T). Femoral arterial smooth muscle responsiveness to KCl, norepinephrine, and calcium (in the presence of either 40 mM KCl or 1 microM norepinephrine) was not altered in SHRSP when compared with WKY. A significant increase in the sensitivity of femoral arteries to KCl and calcium (in the presence of 40 mM KCl) was seen, however, in SHRSP-T and WKY-T. An increased sensitivity to norepinephrine and calcium (in the presence of 1 microM norepinephrine) was seen only in SHRSP-T. Isoproterenol-induced relaxation was significantly attenuated in both SHRSP and SHRSP-T. Relaxation induced by sodium nitroprusside and calcium (membrane stabilization) was not different between the four groups. These results show that femoral arterial smooth muscle responsiveness to vasoconstrictor stimuli is not altered in SHRSP but that beta-adrenergic-mediated relaxation is attenuated. Antihypertensive treatment resulted in an enhanced responsiveness to these vasoconstrictor stimuli but had no effect on the relaxation properties of femoral arterial smooth muscle.