四乙酰葛根素对离体大鼠胸主动脉环作用初步研究

目的观察四乙酰葛根素（Tp）对离体大鼠胸主动脉环的作用以及作用机制。方法采用大鼠离体胸主动脉环灌流装置,观测四乙酰葛根素对重酒石酸去甲肾上腺素（NA）和氯化钾（Kcl）预收缩主动脉环张力的影响。结果四乙酰葛根素对去甲肾上腺素预收缩主动脉环有明显的舒张作用,与空白对照相比,具有显著性差异（P〈0．01）;由KCl引起主动脉环预收缩,Tp与空白对照相比,具有统计学差异（P〈0．01）,对内皮完整血管环的舒张作用明显强于去内皮血管环（P〈0．01）;Tp对NA在无钙液及正常钙液所致离体血管环收缩的舒张作用不明显（P〉O．05）。结论四乙酰葛根素的舒血管作用与受体依赖性钙通道和电压依赖性钙通道均有关,并且其舒血管作用可能与内皮有一定关系。     

越橘乙醇提取物诱导血管舒张的实验研究

目的探讨越橘乙醇提取物对血管内皮的舒张作用及其机制。方法以大鼠胸主动脉为标本,观察越橘提取物对去氧肾上腺素（PE）预收缩血管的舒张作用及其在血管内皮、平滑肌细胞中作用的机制。结果越橘提取物对由去氧肾上腺素（1．0×10^-5mol／L）引发的血管收缩具有浓度依赖性的松弛作用（P〈0．01）,去除血管内皮后舒张作用明显被抑制（P〈0．01）;在内皮完整的血管条中,舒张作用明显被一氧化氮合酶抑制剂L-N-硝基精氨酸甲酯（L—NAME）、亚甲蓝和鸟苷酸环化酶抑制剂（ODQ）所抑制（P〈0．01）,血管的舒张作用因维拉帕米浓度的增加而减弱,并且不受吲哚美辛、格列苯脲、四乙基铵、阿托品和普萘洛尔等药物的影响（P〈0．01）。结论越橘提取物具有明显舒张离体血管的作用,其松弛血管的作用是通过内皮依赖的一氧化氮-环鸟苷酸信号转导系统信号途径,还有可能涉及到L-Ca^2＋通道。     

Elevation of an endogenous inhibitor of nitric oxide synthase in diabetic rat serum

目的：测定糖尿病大鼠血中内源性ＮＯ合酶抑制物二甲基精氨酸（ＤＭＡ）的含量．方法：在链佐星诱发的糖尿病大鼠测定血清ＤＭＡ的含量和乙酰胆碱（ＡＣｈ）诱导血管内皮依赖性舒张．结果：与对照组相比，糖尿病大鼠ＤＭＡ血清浓度显著增加（５４±１０ｖｓ０７±０３μｍｏｌ·Ｌ－１，Ｐ＜００１）；丙二醛含量也高于对照组（２５±０３ｖｓ１５±０１μｍｏｌ·Ｌ－１，Ｐ＜００１）；糖尿病大鼠ＡＣｈ舒血管效应减弱，其作用可被左旋精氨酸所改善．结论：链佐星诱发糖尿病大鼠高血糖症引起内源性ＤＭＡ含量升高，同时血管内皮依赖性舒张功能被削弱．     

壳聚糖对2型糖尿病大鼠主动脉功能的影响

目的观察壳聚糖对2型糖尿病大鼠不同病程主动脉功能的影响。方法取Wistar大鼠40只,采用高能量饮食加腹腔注射链脲佐菌素（STZ）的方法建立2型糖尿病（NIDDM）模型;注射STZ8周和16周后,测定各组离体大鼠胸主动脉环对苯肾上腺素（Phe）和氯化钾（KCl）诱导的收缩反应以及对乙酰胆碱（Ach）诱导的内皮依赖性血管舒张反应的值。结果注射STZ8周后,与正常对照组相比,糖尿病模型组主动脉环对Phe和KCl的反应的收缩张力开始逐渐增高,内皮依赖性血管舒张反应逐渐减小;注射STZ16周后,大剂量壳聚糖组同期主动脉环对KCl的反应幅度逐渐减小,最大收缩张力与糖尿病模型组同期比较有显著性差异（P〈0.05）。结论壳聚糖具有预防和治疗糖尿病大鼠动脉血管病变的作用。     

黄芩苷对离体大鼠胸主动脉的舒张作用及机制

研究黄芩苷对大鼠离体胸主动脉环的舒张作用并探讨其可能的机制。记录去甲肾上腺素(NE)和KCl预收缩的大鼠离体主动脉环张力变化,观察黄芩苷的舒血管作用及不同工具药对其影响。实验发现黄芩苷对NE和KCl引起的去内皮和内皮完整大鼠胸主动脉环的收缩均有舒张作用;L-硝基精氨酸甲酯、亚甲蓝不能抑制黄芩苷对大鼠胸主动脉环的舒张作用,吲哚美辛能显著抑制;钾离子通道阻断剂4-氨基吡啶、四乙基胺、BaCl2不能抑制黄芩苷对胸主动脉环的舒张作用,格列苯脲能抑制黄芩苷的舒张作用;无钙环境下,黄芩苷预处理对NE收缩有明显抑制作用。因此,黄芩苷具有浓度依赖性血管舒张作用,此作用具有内皮依赖性和非内皮依赖性特点,内皮依赖性收缩可能与前列环素途径有关,非内皮依赖机制可能与KATP通道及钙离子通道有关。     

Relationship between calcitonin gene-related peptide and endothelium-dependent vasorelaxation in streptozotocin-induced diabetic rats

在糖尿病大鼠，检测血浆降钙素基因相关肽（ＣＧＲＰ）含量的变化，并探讨其与血管内皮舒张功能的关系．糖尿病大鼠血浆ＣＧＲＰ的含量显著低于对照组（０．２２±０．０８ｖｓ０．３７±０．１３μｇ·Ｌ－１，Ｐ＜０．０１），但丙二醛含量显著增加；糖尿病大鼠胸主动脉对乙酰胆碱诱导内皮依赖性舒张反应显著降低．结果提示：糖尿病大鼠血管内皮舒张功能的削弱与血浆ＣＧＲＰ含量的下降有关．     

甘附冲剂抗大鼠心动过缓作用

目的：研究甘附冲剂（ganfu granule）抗心动过缓作用及作用机制。方法：用普萘洛尔（Pro）和乙酰胆碱制备大鼠心率减慢模型；用硫代巴比妥法测定脂质过氧产物丙二醛（MOA）含量，用Green法测NO的含量。结果：30～270mg／kg甘附冲剂可显著抑制Pro引起的大鼠心率减慢作用（P〈0．05或P〈0．01），并缩短乙酰胆碱引起的大鼠心动过缓的持续时间（P〈0．05或P〈0．01）；30、90、270mg／kg甘附冲剂可显著增加大鼠心肌组织中NO含量（P〈0．05或P〈0．01）和降低大鼠心肌组织中MDA含量的增高（P〈0．05或P〈0．01）。结论：甘附冲剂有明显的抗心动过缓作用，其作用与适度增加心肌中NO含量和抑制脂质过氧化有关。     

2型糖尿病血管内皮功能与胰岛素抵抗的关系研究

目的：了解2型糖尿病患者内皮功能损害的差异,并探讨其与胰岛素抵抗之间的关系。方法选择有或无血管并发症的2型糖尿病患者共88例,年龄、体重指数相匹配的健康对照44例。采用高分辨血管超声仪测定肱动脉血流介导的内皮依赖性血管舒张功能（ FMD）和硝酸甘油介导的非内皮依赖性血管舒张功能（ GTN）。同时测定受试者的血压、血糖、糖化血红蛋白、血脂及空腹C肽。结果（1）糖尿病组与对照组比较,胰岛素抵抗指数（ HOMA－CR）、收缩压、舒张压、空腹血糖、HbA1c、TC、TG、LDL－C均明显升高（P＜0．01或P＜0．05）,胰岛β细胞功能（HOMA－β）、HDL－C明显降低（P＜0．01）。在糖尿病2组之间,收缩压、舒张压、HbA1c、病程,有并发症组明显高于无并发症组（P＜0．01）,而HOMA－CR 2组之间无差异;HOMA－β有并发症组明显低于无并发症组（P＜0．01）。（2）糖尿病组的FMD和GTN明显低于对照组（P＜0．05或P＜0．01）,有血管并发症组更显著低于无并发症组（P＜0．01）。HOMA－CR与FMD和GTN存在负相关;HOMA－β与FMD和GTN存在正相关。基础血管内径三组间差异无显著性（P＞0．05）。结论2型糖尿病患者血管内皮功能明显降低,胰岛素抵抗是导致血管内皮功能障碍加重的危险因素。随着病程的延长,有血管并发症患者内皮功能降低更显著。     

Ⅱ型糖尿病大鼠不同病程期主动脉功能的改变

目的：观察Ⅱ型糖尿病大鼠不同病程期血管对收缩剂的反应性及内皮依赖性血管舒张反应(EDVR)的改变。方法：采用高能量饮食加小剂量腹腔注射链脲佐菌素(STZ)的方法，建立Ⅱ型糖尿病大鼠模型；观察注射STZ后12和20周离体大鼠胸主动脉对苯肾上腺素(Phe)和氯化钾(KCl)引起收缩的反应性以及乙酰胆碱(Ach)引起的EDVR反应的改变。结果：注射STZ后12周，主动脉对Phe的反应性增强，对KCl的反应性不变，EDVR轻度受损；注射STZ后20周，对Phe的反应性进一步提高，对KCl的反应性显著增强，EDVR明显受损。结论：Ⅱ型糖尿病大鼠大血管对血管收缩物质的反应性增强，而EDVR则减弱，随着病程的发展这些改变进一步增加。     

三精锐普降糖仪在糖尿病治疗过程中胰高血糖素水平的变化

目的：观察三精锐普降糖仪在治疗糖尿病过程中血胰高血糖素的变化；方法：（1）临床实验观察了12名非胰岛素依赖性糖尿病（NIDDM）患者治疗前后空腹血糖（FBS），胰高血糖素水平的变化；（2）动物实验：取32只Wistar大鼠分为4组：A正常对照组，B糖尿病对照组，C糖尿病大鼠治疗一次组，D糖尿病大鼠治疗10次组，在治疗前后分别测FBS作自身对照，同时在治疗前后测胰高血糖素作组间对照；结果：（1）临床经验：FBS在治疗后显著降低（P＜0．05），胰高血糖素在治疗后下降（P＜0．05），（2）动物实验：A，B，C组FBS无显著性改变（P＜0．05），D组在治疗后FBS下降（P＜0．05），胰高血糖与B组比较上升（P＜0．05）；结论：三精锐普降糖仪通过降低胰高血糖的水平对血糖素的水平对糖尿病患者及大鼠有一定的治疗作用。     

糖尿病大鼠血中内源性一氧化氮合酶抑制物增高

目的：测定糖尿病大鼠血中内源性ＮＯ合酶抑制物二甲基精氨酸（ＤＭＡ）的含量，方法：在链佐星诱发的糖尿病大鼠测定血清ＤＭＡ的含量和乙酰胆碱（ＡＣｈ）诱导血管内皮依赖性舒张，结果：与对照组相比，糖尿病大鼠ＤＭＡ血清浓度显增加（５．４±１．０ｖｓ０．７±０．３μｍｏｌ．Ｌ＾－１，Ｐ〈０．０１）；丙二醛含量也高于对照组（２．５±０．３ｖｓ２１．５±０．１μｍｏｌ．Ｌ＾－１，Ｐ〈０．０１）；糖尿病大鼠ＡＣｈ     

Relationship between peroxisome proliferator-activated receptors (PPAR alpha and PPAR gamma) and endothelium-dependent relaxation in streptozotocin-induced diabetic rats

(1) The aim of the present study was to investigate the causal relationship between peroxisome proliferator-activated receptor (PPAR) and endothelium-dependent relaxation in streptozotocin (STZ)-induced diabetic rats. (2) Acetylcholine (ACh)-induced endothelium-dependent relaxation was significantly weaker in diabetic rats than in age-matched controls. The decreased relaxation in diabetes was improved by the chronic administration of bezafibrate (30 mg kg-1, p.o., 4 weeks). (3) The expressions of the mRNAs for PPARalpha and PPARgamma were significantly decreased in STZ-induced diabetic rats (compared with the controls) and this decrease was restored partially, but not completely, by the chronic administration of bezafibrate. (4) Superoxide dismutase activity in the aorta was not significantly different between diabetic rats and bezafibrate-treated diabetic rats. (5) The expression of the mRNA for the p22phox subunit of NAD(P)H oxidase was significantly higher in diabetics than in controls, but it was lower in bezafibrate-treated diabetic rats than in nontreated diabetic rats. Although the expression of the mRNA for prepro ET-1 (ppET-1) was markedly increased in diabetic rats (compared with controls), this increase was prevented to a significant extent by the chronic administration of bezafibrate. (6) These results suggest that downregulations of PPARalpha and PPARgamma may lead to an increased expression of ppET-1 mRNA in diabetic states and this increment may trigger endothelial dysfunction.     

Effects of chronic administration of fruit extract (Citrus unshiu Marc) on endothelial dysfunction in streptozotocin-induced diabetic rats

We investigated the effects of chronic administration of fruit extract (Citrus unshiu MARC) on the endothelial dysfunction seen in aortae from streptozotocin (STZ)-induced diabetic rats. A ten-week administration of this fruit extract preserved acetylcholine (ACh)-induced endothelium-dependent relaxation, but not sodium nitroprusside (SNP)-induced endothelium-independent relaxation, in the diabetic aorta. In age-matched control rats, chronic administration of the fruit extract had no influence on the ACh- or SNP-induced aortic relaxation. The increased total cholesterol, low-density lipoprotein (LDL) cholesterol, and triglyceride levels seen in STZ-induced diabetic rats were not normalized by fruit-extract treatment. These results suggest that Citrus unshiu MARC extract preserves endothelial function in the aorta in STZ-induced diabetic rats without lowering plasma cholesterol. This beneficial effect may be due to this extract protecting of nitric oxide against inactivation by oxygen free radicals.     

Salvianolic acid A protects against vascular endothelial dysfunction in high-fat diet fed and streptozotocin-induced diabetic rats

Salvianolic acid A (SalA) is one of the main active ingredients of Salvia miltiorrhizae. The objective of this study was to evaluate the effect of SalA on the diabetic vascular endothelial dysfunction (VED). The rats were given a high-fat and high-sucrose diet for 1 month followed by intraperitoneal injection of streptozotocin (30 mg/kg). The diabetic rats were treated with SalA (1 mg/kg, 90% purity) orally for 10 weeks after modeling, and were given a high-fat diet. Contractile and relaxant responses of aorta rings as well as the serum indications were measured. Our results indicated that SalA treatment decreased the level of serum Von Willebrand factor and ameliorated acetylcholine-induced relaxation and KCl-induced contraction in aorta rings of the diabetic rats. SalA treatment also reduced the serum malondialdehyde, the content of aortic advanced glycation end products (AGEs), and the nitric oxide synthase (NOS) activity as well as the expression of endothelial NOS protein in the rat aorta. Exposure of EA.hy926 cells to AGEs decreased the cell viability and changed the cell morphology, whereas SalA had protective effect on AGEs-induced cellular vitality. Our data suggested that SalA could protect against vascular VED in diabetes, which might attribute to its suppressive effect on oxidative stress and AGEs-induced endothelial dysfunction.     

Impairment of endothelium-dependent relaxation and changes in levels of cyclic GMP in aorta from streptozotocin-induced diabetic rats.

1. Acetylcholine (ACh)-induced relaxation of aortic strips with endothelium and production of cyclic GMP between streptozotocin-induced diabetic and age-matched control rats were compared. 2. The concentration-response curve for ACh-induced relaxation was shifted to the right in diabetic rats. IC50 values for ACh were 4.57 +/- 0.67 x 10(-8) M and 1.00 +/- 0.87 x 10(-7) M in aortic strips from age-matched control and diabetic rats, respectively (n = 6, P less than 0.05). 3. Relaxations produced by atrial natriuretic peptide (ANP) in diabetic aortae were similar to those in age-matched vessels. 4. Relaxations produced by sodium nitroprusside (SNP) in diabetic aortae were similar to those in age-matched vessels. 5. Basal levels of cyclic GMP and ACh-induced production of cyclic GMP were significantly decreased in diabetic rats. 6. These results suggest that functional changes in endothelium but not in guanylate cyclase activity in the aorta may occur in diabetes, and thus, spontaneous and ACh-induced formation of cyclic GMP may be decreased. This decrease in production of cyclic GMP may be responsible for the decreased response of the aorta to the relaxant effect of ACh.     

Salvianolic acid A protects against vascular endothelial dysfunction in high-fat diet fed and streptozotocin-induced diabetic rats

Salvianolic acid A (SalA) is one of the main active ingredients of Salvia miltiorrhizae. The objective of this study was to evaluate the effect of SalA on the diabetic vascular endothelial dysfunction (VED). The rats were given a high-fat and high-sucrose diet for 1 month followed by intraperitoneal injection of streptozotocin (30 mg/kg). The diabetic rats were treated with SalA (1 mg/kg, 90% purity) orally for 10 weeks after modeling, and were given a high-fat diet. Contractile and relaxant responses of aorta rings as well as the serum indications were measured. Our results indicated that SalA treatment decreased the level of serum Von Willebrand factor and ameliorated acetylcholine-induced relaxation and KCl-induced contraction in aorta rings of the diabetic rats. SalA treatment also reduced the serum malondialdehyde, the content of aortic advanced glycation end products (AGEs), and the nitric oxide synthase (NOS) activity as well as the expression of endothelial NOS protein in the rat aorta. Exposure of EA.hy926 cells to AGEs decreased the cell viability and changed the cell morphology, whereas SalA had protective effect on AGEs-induced cellular vitality. Our data suggested that SalA could protect against vascular VED in diabetes, which might attribute to its suppressive effect on oxidative stress and AGEs-induced endothelial dysfunction.     

Changes in superoxide dismutase mRNA expression by streptozotocin-induced diabetes.

1. Experiments were designed to investigate the involvement of superoxide anions in the attenuated endothelium-dependent relaxation of the rat aorta from streptozotocin (STZ)-induced diabetic rats. 2. The endothelium-dependent relaxation responses to acetylcholine (ACh, 10(-7) M) in helical strips of the aorta precontracted with noradrenaline (NA, 5 x 10(-3) approximately 3 x 10(-7) M) were significantly decreased in STZ-induced diabetic rats. The recovery phase of the relaxation after single administration of ACh in the STZ-induced diabetic rats was more rapid than those in control vessels. 3. Preincubation of aortic strips with superoxide dismutase (SOD, 60 u ml-1) normalized the recovery phase of the relaxation of diabetic aorta after single administration of ACh, whereas catalase (150 u ml-1) or indomethacin (10(-5) M) had no effects on the relaxation. 4. SOD (180 u ml-1) caused relaxation in NA precontracted aortic strips and the degree of the SOD-induced relaxation was significantly greater in diabetic aorta as compared with age-matched control vessels. 5. When the changes in mRNA expressions of Mn-SOD or Cu-Zn-SOD were observed, Mn-SOD mRNA expression was markedly decreased, and Cu-Zn-SOD was slightly decreased in diabetic aorta. 6. These results suggest that the rapid destruction of NO by superoxide anions may occur in the STZ-induced diabetic rats, and this may be due to a decrease in mRNA expression of Mn-SOD or Cu-Zn-SOD.     

Impaired endothelium-dependent relaxation in isolated resistance arteries of spontaneously diabetic rats.

1. Previous studies have shown that endothelium-dependent relaxation in the aorta of spontaneously diabetic bio bred rats (BB) is impaired. 2. We have investigated noradrenaline (NA) contractility, endothelium-dependent acetylcholine (ACh) and bradykinin (BK) relaxation, and endothelium-independent sodium nitroprusside (SNP) relaxation in mesenteric resistance arteries of recent onset BB rats and established insulin treated BB rats, compared to their age-matched non diabetic controls. 3. There was no significant difference in the maximum contractile response or sensitivity to noradrenaline in either of the diabetic groups compared to their age-matched controls. 4. Incubation with the nitric oxide synthetase inhibitor NG-nitro-L-arginine (L-NOARG) resulted in a significant increase in maximum contractile response to noradrenaline in the recent onset age-matched control group (P < 0.05). Analysis of the whole dose-response curve (using ANOVA for repeated measures with paired t test) showed a significant left-ward shift following the addition of L-NOARG (P < 0.001). A similar but less marked shift (P < 0.01) was evident in vessels from recent onset diabetics. An overall shift in both sensitivity and maximum response was also evident in the age-matched non diabetic controls of the insulin-treated group (P < 0.05). However, by contrast, there was no significant change in sensitivity in the insulin-treated diabetic rats. 5. ACh-induced endothelium-dependent relaxation was significantly impaired in the recent onset diabetic rats compared to their age-matched controls (47 +/- 11% versus 92 +/- 2%, P < 0.05, n = 6), and in the insulin treated diabetic rats (34 +/- 5% versus 75 +/- 6%, P < 0.05, n = 6). The relaxation responses to BK also were significantly impaired in the diabetic rats compared to their age-matched controls (recent onset: 20 +/- 3% versus 72 +/- 7%, P < 0.05, n = 6; insulin treated: 12 +/- 9% versus 68 +/- 7%, P < 0.05, n = 7). 6. Incubation with either the nitric oxide synthetase substrate, U-arginine, or the free radical scavenging enzyme superoxide dismutase (150 mu ml-1) failed to improve the attenuated response of acetylcholine-induced relaxation in the diabetic vessels. 7. Endothelium-dependent relaxation mediated by ACh and BK was significantly attenuated in both the diabetic and control vessels after incubation with L-NOARG. 8. Pretreatment with a cyclo-oxygenase inhibitor, indomethacin, significantly enhanced the relaxation to ACh in both the recent onset and insulin treated diabetic rats (42 +/- 10%, n = 7 versus 64 +/- 7%, n = 7, P < 0.05, and 40 +/- 5%, n = 7 versus 65 +/- 9%, n = 6, P < 0.05). 9. Following endothelium removal, there was a marked impairment in endothelium-dependent relaxation responses to ACh and BK in both the diabetic and control vessels. 10. Incubation with the thromboxane A2 receptor antagonist SQ29548, did not significantly improve the ACh endothelium-dependent relaxation response in the diabetic vessels. 11. Endothelium-independent relaxation to sodium nitroprusside was significantly impaired in the first group of diabetic vessels studied; however, subsequent studies showed no impairment of the sodium nitroprusside response in the diabetic vessels. 12. In conclusion, the ability of the endothelium to regulate vascular contractility is reduced in recent onset diabetic vessels, and significantly impaired in established insulin treated diabetics. Relaxation to the endothelium-dependent vasodilators ACh and BK was impaired in both the recent onset and the established insulin treated diabetics, and the ACh response was significantly improved following pretreatment with indomethacin, suggesting a role for a cyclo-oxygenase-derived vasoconstrictor. Preliminary studies with a thromboxane A2, receptor antagonist, SQ29548 did not significantly improve the impaired relaxation to ACh, indicating that the vasoconstrictor prostanoid is not thromboxane A2.     

The effects of chronic L-arginine treatment on vascular responsiveness of streptozotocin-diabetic rats.

In this study, the protective effects of L-arginine treatment in vivo on vascular reactivity of streptozotocin (STZ)-induced 12-week-old diabetic rats were examined. Loss of weight, polydipsia, polyphagia, hyperglycemia, hypoinsulinemia, and elevated levels of plasma cholesterol and triglyceride were observed in diabetic rats. L-arginine treatment (1 mg/mL in drinking water) did not significantly affect these metabolic and biochemical abnormalities. Plasma malondialdehyde (MDA) levels in untreated diabetic rats were also significantly higher than untreated controls. However, L-arginine treatment prevented the increase in MDA level of plasma of diabetic rats. Contractile responses, but not sensitivity to noradrenaline (NA), were significantly increased in diabetic rats compared to controls. Treatment of diabetic rats with L-arginine completely prevented the increase in NA responses. Relaxation response to acetylcholine (ACh), but not to sodium nitroprusside (SNP), in diabetic aorta has been found to be significantly decreased as compared with controls. However, there were no significant differences in pD2 values of acetylcholine in either of the groups. L-arginine treatment increased the ACh responses to the control level. All effects of L-arginine on vascular reactivity were found to be specific for diabetic rats and not controls. These results suggest that functional abnormalities occurred in aorta from diabetic rat might at least in part result from L-arginine deficiency, and the lipid peroxidation-lowering effect of L-arginine may account for its protective effect on vascular reactivity of diabetic rats.     

Endothelial function in mesenteric resistance arteries from the genetically hypertensive rat

1. Endothelial function in mesenteric resistance arteries (MRA) from male 12-week-old New Zealand genetically hypertensive (GH) rats and their normotensive control strain (N) was compared in vessels mounted on a wire myograph and by the production of intracellular cGMP. In parallel experiments, MRA from the spontaneously hypertensive (SHR) rat strain, in which there is an endothelial defect, and from GH rats, in which an endothelial defect was induced by chronic nitric oxide synthase (NOS) inhibition with Nomega-nitro-L-arginine methyl ester (L-NAME), were studied. 2. Contractile responses to potassium (124 mmol/L) depolarization and to NA (10(-8) to 10(-4) mol/L) were similar in GH and N rats; however, in SHR, enhanced contractile responses were found (P < 0.05). The endothelium-dependent relaxation induced by acetylcholine (ACh; 10(-9) to 10(-4) mol/L) and endothelium- independent relaxation induced by sodium nitroprusside (SNP; 10(-9) to 10(-4) mol/L) were identical in preparations from GH and N. A significantly attenuated (P < 0.01) vasodilator response to ACh was observed in preparations from SHR. 3. Levels of intracellular cGMP were similar in untreated small mesenteric arterial trees from GH, N and SHR rats. Acetylcholine (10-5 mol/L) significantly (P < 0.001) increased the cGMP content in both GH and N rats. A non-significant increase occurred in cGMP content in preparations from SHR. 4. In GH rats given L-NAME (10 mg/kg per day for up to 5 weeks), an attenuated (P < 0.01) endothelium-dependent relaxation to ACh and an enhanced (P < 0.01) endothelium- independent relaxation to SNP were observed. Lower basal cGMP levels were found in preparations from L-NAME-treated GH rats and ACh (10-5 mol/L) failed to significantly elevate the cGMP content in these preparations. 5. These experiments failed to show evidence of reduced endothelial function in GH rats, although an endothelial defect in SHR rats and after NOS inhibition in GH rats could be demonstrated.