Apocynin but not allopurinol prevents and reverses adrenocorticotropic hormone-induced hypertension in the rat

BACKGROUND: Adrenocorticotropic hormone (ACTH)-induced hypertension in the rat is accompanied by increased oxidative stress. This study examines the enzymatic source of reactive oxygen species in ACTH-hypertension. METHODS: Male Sprague-Dawley rats were divided into 10 groups of 10-20 rats per group. The NAD(P)H oxidase inhibitor apocynin (1.5 mmol/L in drinking water) or the xanthine oxidase inhibitor allopurinol (200 mg/kg/day via food) were administered daily. After 4 days, rats were co-administered ACTH (0.2 mg/kg/day) or saline by subcutaneous injection daily for 11 days (prevention study). In a reversal study, ACTH/saline was administered for 13 days and from day 8, apocynin or allopurinol was added for 5 days. Systolic blood pressure (SBP) was measured by the tail-cuff method and oxidative stress using plasma F2-isoprostane concentrations. Results were expressed as mean+/-SEM. RESULTS: ACTH increased SBP (P<.001) but apocynin or allopurinol alone had no effect. Apocynin (but not allopurinol) co-treatment prevented (142+/-3 ACTH, 120+/-4 mm Hg apocynin+ACTH, P'<0.001) and reversed ACTH-induced hypertension (133+/-4 to 118+/-5 mm Hg, P<.05). Plasma F2-isoprostane concentrations were increased in ACTH-treated rats compared with saline (11.9+/-1.0 vs 8.2+/-0.8 nmol/L, P<.01), and apocynin attenuated the ACTH-induced rise in plasma F2-isoprostane concentrations. Serum urate concentrations were undetectable in 75% of rats treated with allopurinol and were not affected by ACTH. CONCLUSIONS: Apocynin but not allopurinol prevented and reversed ACTH-induced hypertension in the rat. These results suggest superoxide production through NAD(P)H oxidase plays a role in ACTH-induced hypertension.     

Folic acid prevents and partially reverses glucocorticoid-induced hypertension in the rat

BACKGROUND: To investigate the effect of folic acid on the increased pressure in rats treated with either adrenocorticotropic hormone (ACTH) or dexamethasone (Dex), and to further investigate the role of tetrahydrobiopterin (BH(4)) in any effect of folic acid by comparing the effect of BH(4) with that of folic acid in Dex hypertension. METHODS: Male Sprague-Dawley (SD) rats were treated with saline, subcutaneous ACTH (0.2 mg/kg/d) or Dex (10 microg/rat/d). Folic acid (0.04 g/L drinking) or BH(4) (10 mg/kg/d intraperitoneally) was started before (prevention) and during (reversal) glucocorticoid treatment. RESULTS: Saline, BH(4), vehicle for BH(4), or folic acid alone did not change systolic blood pressure (BP). Systolic BP was increased by ACTH and Dex. Folic acid, but not BH(4), prevented the development of hypertension caused by ACTH and Dex treatment. The ACTH and Dex hypertension were partially reversed by folic acid. The BH(4) increased plasma total biopterin concentrations. The Dex decreased plasma NOx concentrations but had no effect on plasma biopterin concentrations. The ACTH and Dex increased plasma F(2)-isoprostane concentrations and decreased serum homocysteine concentrations compared with control but had no effect on serum folate concentrations. Folic acid increased serum folate concentrations compared with control but had no effect on homocysteine concentrations. CONCLUSIONS: Folic acid prevented and partially reversed both ACTH and Dex hypertension in rats without modifying the increase in plasma F(2)-isoprostane concentrations. Given that BH(4) failed to prevent ACTH or Dex hypertension, folic acid is unlikely to be acting through increased BH(4) production. The precise mechanism for the BP-lowering effect of folic acid in this model of hypertension remains to be determined.     

The anti-oxidant Tempol reverses and partially prevents adrenocorticotrophic hormone-induced hypertension in the rat

OBJECTIVE: To investigate the effects of the antioxidant Tempol on prevention and reversal of adrenocorticotrophic hormone (ACTH)-induced hypertension in the rat, a model of hypertension characterized by nitric oxide deficiency. METHODS: Male Sprague-Dawley rats (n = 10 in each group) were treated with either saline or ACTH (0.2 mg/kg per day, s.c.) for 12 days. Tempol (1 mmol/l in drinking water) treatment was started on either day 8 (T8) of ACTH or saline treatment (reversal study), or 4 days prior to ACTH or saline treatment (prevention study). Systolic blood pressure (SBP) was measured using tail-cuff sphygmomanometry. Plasma F2-isoprostanes, a marker of oxidative stress, were measured by gas chromatography-mass spectrometry. RESULTS: ACTH increased SBP (mean +/- SEM: 119 +/- 5 to 147 +/- 7 mmHg, P < 0.0005) and plasma F2-isoprostane concentration (8.4 +/- 1.2 saline versus 12.9 +/- 1.6 nmol/l ACTH, P < 0.05). Tempol alone did not alter SBP, but administration of Tempol on T8 reversed ACTH-induced hypertension (from 134 +/- 4 T8 to 118 +/- 3 mmHg, P < 0.005). Tempol pre-treatment partially prevented ACTH-induced hypertension (123 +/- 2 mmHg, P' < 0.05). However, Tempol had no effect on F2-isoprostane concentrations at the dose used in this study. CONCLUSIONS: ACTH-induced hypertension in the rat is associated with increased oxidative stress. Tempol treatment reversed, and pretreatment partially prevented ACTH-induced hypertension, independent of improvement in systemic oxidative stress.     

The antioxidant tempol prevents and partially reverses dexamethasone-induced hypertension in the rat

BACKGROUND: Many forms of hypertension are associated with increased oxidative stress. This study investigated the effects of Tempol, a superoxide scavenger, on prevention and reversal of hypertension induced by the synthetic glucocorticoid dexamethasone (Dex) in the rat. METHODS: Male Sprague-Dawley rats (n = 10 in each group) were treated with saline or Dex (10 microg/kg/day subcutaneously) for 13 days. Tempol (1 mmol/L) was given in drinking water from 4 days before treatment (prevention) or from treatment day 8 (T8) (reversal). Systolic blood pressure (SBP) was measured by the tail-cuff method. Plasma F(2)-isoprostane concentrations were measured as a highly specific marker of oxidative stress. Thymus weight was measured as a marker of glucocorticoid activity. RESULTS: Dex treatment increased SBP (122 +/- 5 to 136 +/- 3 mm Hg, P <.05) and plasma F(2)-isoprostane concentrations (P =.005). Tempol alone did not alter SBP, but Tempol pretreatment prevented Dex-induced hypertension compared with that in rats treated with Dex alone (128 +/- 4 and 144 +/- 7 mm Hg respectively, P' <.05). Tempol partially reversed Dex-induced hypertension (122 +/- 5 and 136 +/- 3 mm Hg, respectively, P' =.057). Thymus weight was decreased in Dex-treated rats compared with saline treated rats (157 +/- 10 saline and 105 +/- 6 mg/100 g body weight Dex, P <.0005). Tempol affect neither thymus weight nor F(2)-isoprostane concentrations. CONCLUSIONS: Chronic Dex treatment increased SBP and tended to increase oxidative stress shown as increased plasma F(2)-isoprostane concentrations. Tempol prevented and partially reversed Dex-induced hypertension, independent of improvement in systemic oxidative stress measured by F(2)-isoprostane concentrations.     

Role of tetrahydrobiopterin in adrenocorticotropic hormone-induced hypertension in the rat

Adrenocorticotropic hormone (ACTH)-induced hypertension in the rat is characterized by nitric oxide deficiency. Tetrahydrobiopterin (BH4) is an essential cofactor for the enzyme nitric oxide synthase and glucocorticoids have been reported to reduce cytokine-induced BH4 production. Accordingly we hypothesized that ACTH-induced hypertension would be reversed by BH4 supplementation. Male Sprague-Dawley rats (n = 33) were treated with BH4 in vehicle (10 mg/kg/day i.p.) or vehicle alone (5 mg/kg/day i.p. of ascorbic acid in 4 mM HCl) for 10 days. ACTH (0.2 mg/kg s.c.) or saline daily injection was started 2 days after BH4 or vehicle treatment and continued for 8 days. Systolic blood pressure (SBP) was measured on alternate days using the tail cuff method. Treatment with HCl, ascorbic acid or BH4 alone had no effect on SBP. In saline treated rats, neither BH4 nor its vehicle modified SBP. In ACTH treated rats, SBP was increased in both BH4 (from 128 +/- 6 to 142 +/- 4 mmHg, T0 to T10, P < 0.0005, one way ANOVA) and vehicle groups (from 127 +/- 3 to 158 +/- 7 mmHg, T0 to T10, P < 0.001, one way ANOVA). There was no significant difference in SBP between BH4 + ACTH treated and vehicle + ACTH treated rats. Thus, daily injection of BH4 (10 mg/kg i.p.) failed to prevent the development of ACTH-induced hypertension in rat.     

Lipopolysaccharide reverses adrenocorticotrophic hormone-induced hypertension in the rat.

Lipopolysaccharide (LPS) was used to stimulate nitric oxide (NO) release and investigate the effect of endogenous NO on adrenocorticotrophic hormone (ACTH)-induced hypertension in rats. After preliminary studies to determine the appropriate dose of LPS, 40 male Sprague-Dawley rats were treated with ACTH (200 microg/kg/day, s.c.) or saline (sham) for 8 days and then given a single dose of LPS (10 mg/kg, i.p.) or saline. ACTH treatment was continued for a further 5 days. Systolic blood pressure (SBP) was measured daily using the tail cuff method. Results were expressed as the mean +/- SEM. ACTH treatment significantly increased SBP (from 105 +/- 3 to 129 +/- 4 mmHg; p<0.05), whereas saline had no effect on SBP. The ACTH-induced increase in SBP was reversed by LPS injection (from 125 +/- 6 to 102 +/- 7 mmHg; p<0.05). SBP was also decreased in sham + LPS-treated rats compared with that of sham + saline-treated rats (p<0.05), but the SBP change in response to LPS was greater in ACTH-treated than in sham-treated rats (-23 vs. -8 mmHg; p<0.05). These data are compatible with the notion that reduced NO availability plays a role in ACTH-induced hypertension.     

Apocynin but not L-arginine prevents and reverses dexamethasone-induced hypertension in the rat

BACKGROUND: Dexamethasone (Dex)-hypertension in rats is associated with increased oxidative stress. We investigated effects of the NAD(P)H oxidase inhibitor apocynin and the nitric oxide (NO) precursor L-arginine on Dex-hypertension to determine the relative roles of NAD(P)H oxidase and uncoupling in the reactive oxygen species (ROS) generation and hypertension. METHODS: Male Sprague-Dawley rats (n = 10/group) received Dex (20 microg/kg/day subcutaneously) or saline (vehicle) for 14 days. In a prevention study, rats received 4 days of apocynin treatement (1.5 mmol/L in drinking water) followed by Dex/saline for 12 days. In reversal studies, apocynin or L-arginine was given from day 8 to 14. Systolic blood pressure (SBP) was measured by tail cuff, and thymus weight was used as a marker of glucocorticoid activity. RESULTS: Administration of Dex increased SBP (104 +/- 3 to 122 +/- 3 mm Hg, P < .01, mean +/- SEM) and decreased thymus and body weight (P' < .05). Apocynin alone had no effect on SBP, BW, or thymus weight. Apocynin prevented (122 +/- 4 Dex, 111 +/- 3 mm Hg Apocynin+Dex, P' < .05) and reversed Dex-hypertension (130 +/- 4 to 116 +/- 4 mm Hg, P < .01). L-arginine did not reverse Dex-hypertension. CONCLUSIONS: In male SD rats, apocynin but not l-arginine prevented and reversed Dex-hypertension, suggesting that NAD(P)H oxidase-mediated superoxide production but not endothelial nitric oxide synthase uncoupling is important in Dex-hypertension.     

L-arginine partially reverses established adrenocorticotrophin-induced hypertension and nitric oxide deficiency in the rat

BACKGROUND: L-arginine treatment prevents adrenocorticotrophin (ACTH) induced hypertension in the rat. This study examined whether L-arginine treatment could reverse established ACTH hypertension and its effects on markers of decreased NO activity. METHODS: Sixty-four male Sprague-Dawley rats were randomly divided into 6 groups given 12 days of treatment: (1) sham (0.9% NaCl, 0.5 ml/kg, subcutaneously, sc, n = 16); (2) ACTH (0.5 mg/kg/day, sc, n = 16); (3) sham + L-arginine (0.6% in food, from treatment day 8 onwards, n = 10); (4) ACTH + L-arginine (n = 10); (5) sham + D-arginine (0.6% in food, from T 8 onwards) (n = 6); and (6) ACTH + D-arginine (n = 6). Systolic blood pressure, water intake, urine volume, and body weight were measured every second day. At the end of the experiments, plasma and urinary nitrate/nitrite (NOx), plasma amino acid concentrations (in groups 1-4), and urinary cyclic guanosine monophosphate (cGMP) concentrations were measured. RESULTS: Sham, sham + L-arginine, and sham + D-arginine treatments did not affect blood pressure. ACTH increased systolic blood pressure (from 121 +/- 1 to 147 +/- 2 mmHg, p < 0.001, pooled control vs treatment day 12, mean +/- sem), and this was partially reversed by L-arginine (group 4: from 141 +/- 2 on day 8 to 133 +/- 1 mmHg on day 12, n = 10, p < 0.001). In contrast, D-arginine did not affect blood pressure in ACTH-treated rats (group 6). ACTH increased water intake and urine volume and decreased body weight, and L-arginine administration did not alter these parameters. ACTH decreased plasma citrulline (group 1 vs 2: 115 +/- 7 vs 67 +/- 6 micro M/L, n = 16, p < 0.001) and NOx concentrations (group 1 vs 2: 8.3 +/- 0.8 vs 4.5 +/- 0.6 microM/L, n= 10, p < 0.001) and these decreases were reversed by L-arginine treatment (group 4: citrulline 98 +/- 9 micro M/L, NOx 9.1 +/- 1.6 micro M/L, group 2 vs 4, both p < 0.05). ACTH produced marked increases in urinary cGMP excretion (group 1 vs 2: 0.5 +/- 0.1 vs 1.9 +/- 0.4 nmol/24 h, p < 0.01). CONCLUSION: Supplementation with L-arginine partly reversed established ACTH-induced hypertension and restored plasma NOx and citrulline concentrations to levels seen in sham-treated rats. These data are consistent with previous studies suggesting that functional NO deficiency has a role in ACTH-induced hypertension in rats.     

Separate and combined use of Verapamil,Aspirin and Captopril in experimental chronic pulmonary hypertension

Summary In Wistar rats, rendered pulmonary hypertensive by chronic confinement in normobaric hypoxic cages, impairment of transmembrane transport of calcium by Verapamil and blockade of the action of Angiotensin I converting enzyme by Captopril when applied simultaneously did not show an additive effect in reducing the rise of pulmonary artery pressure and decreasing the augmentation of right ventricular mass. Similarly, the action of Verapamil together with decrease of prostaglandin synthetase activity by Aspirin showed no additive effect. Although in this way the results of the present study failed to give substantial support to the idea of the existence of several mediators of hypoxic pulmonary vasoconstriction, they by no means deny this possibility.Part of this study was presented at the Symposium on Primary Pulmonary Hypertension of the Working Group on Pulmonary Circulation of the European Society of Cardiology, March 1982, Vienna.This work was supported by a grant from the Serbian Research Foundation.     

Aspirin attenuates monocrotaline-induced pulmonary arterial hypertension in rats by suppressing the ERK/MAPK pathway

This study aimed to investigate the therapeutic effects of aspirin (ASA) and its potential mechanisms of action in monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH) in rats. PAH was induced in a rat model by a single intraperitoneal (IP) injection of MCT. Saline was injected in a control group. Two weeks following MCT injection, right ventricular systolic pressure (RVSP) and systolic blood pressure (SBP) were measured in six rats from each group to confirm establishment of a PAH model. The remaining MCT-treated rats were randomly allocated to receive IP injection of saline, ASA, or ERK1/2 inhibitor PD98059. Four weeks following treatment, RVSP was measured and all rats were sacrificed for histological study. There was no significant difference in SBP in any group two weeks following MCT administration. Nonetheless RVSP was significantly increased in the MCT group compared with the control group. At 6 weeks, ASA treatment remarkably attenuated MCT-induced increased RVSP, RV hypertrophy, and pulmonary artery remodeling compared with the MCT group. The density of pulmonary capillaries in ASA-treated rats was also dramatically increased. Treatment with ASA significantly inhibited the increased p-ERK1/2 and restored the impaired endothelial nitric oxide synthase (eNOS) in MCT-treated rats. This study demonstrated that ASA distinctively attenuates MCT-induced PAH by inhibition of the ERK1/2 signaling pathway.     

阿司匹林抵抗的临床特征分析

阿司匹林是目前应用最广的心脑血管疾病一二级预防用药.已证实阿司匹林的使用可降低致死性和/或非致死性血管事件的发生率.然而最近关注到,在长期服用阿司匹林的人群中,部分人群仍有血栓形成事件的发生,由此提出阿司匹林抵抗概念.已有多个大型多中心临床试验对阿司匹林抵抗患者的临床特征进行分析,以利于早期对该类患者进行识别.文章对阿司匹林抵抗患者的临床特征及其出现的可能原因进行综述.     

阿司匹林干预野百合碱诱导的大鼠肺动脉高压的研究

目的探讨阿司匹林对野百合碱(MCT)诱导的大鼠肺动脉高压的作用。方法雄性Sprague Dawley(SD)大鼠120只,随机分为6组,每组20只,分别为:正常对照组(Ctrl组)、肺动脉高压组(PAH组)和阿司匹林不同剂量治疗组(ASA 0.5组,ASA 1组,ASA 2组,ASA 4组)。PAH组、阿司匹林各剂量治疗组于第0天一次性腹腔注射MCT 50 mg/kg。从第l天开始,阿司匹林各剂量治疗组分别给予阿司匹林0.5、1.0、2.0 mg·kg~(-1)和4.0mg·kg~(-1)·d~(-1)灌胃,共30d。第31天,对各组大鼠进行以下检测:(1)统计大鼠的体质量和生存率;(2)右心导管法测定肺动脉收缩压(sPAP);(3)心脏大体标本测定右心室肥厚指数(RVHI);(4)肺组织染色切片,运用IPP 6.0图像分析软件测定肺小动脉增厚指数(PATI)。结果与PAH组比较,ASA 2组和ASA 4组体质最增加[(464.6±62.6)g和(473.2±77.2)g比(424.9±68.5)g,均为P<0.05];ASA各治疗组合计生存率较PAH组明显提高(83.75%比60.00%,P<0.05);与PAH组比较,ASA各治疗组sPAP明显下降(均为P<0.05),RVHI显著降低(均为P<0.05);除ASA 0.5组以外,其他阿同匹林治疗组的PATI较.PAH组明显降低(均为P<0.05)。结论阿司匹林1、2 mg·kg~(-1)·d~(-1)和4 mg·kg~(-1)·d~(-1)能有效降低野百合碱诱导的肺动脉高压大鼠的肺动脉压力,减轻右心室肥厚和肺小动脉增生。     

Dehydroepiandrosterone (DHEA) prevents and reverses chronic hypoxic pulmonary hypertension

Pulmonary artery (PA) hypertension was studied in a chronic hypoxic-pulmonary hypertension model (7-21 days) in the rat. Increase in PA pressure (measured by catheterism), cardiac right ventricle hypertrophy (determined by echocardiography), and PA remodeling (evaluated by histology) were almost entirely prevented after oral dehydroepiandrosterone (DHEA) administration (30 mg/kg every alternate day). Furthermore, in hypertensive rats, oral administration, or intravascular injection (into the jugular vein) of DHEA rapidly decreased PA hypertension. In PA smooth muscle cells, DHEA reduced the level of intracellular calcium (measured by microspectrofluorimetry). The effect of DHEA appears to involve a large conductance Ca2+-activated potassium channel (BKCa)-dependent stimulatory mechanism, at both function and expression levels (isometric contraction and Western blot), via a redox-dependent pathway. Voltage-gated potassium (Kv) channels also may be involved because the antagonist 4-amino-pyridine blocked part of the DHEA effect. The possible pathophysiological and therapeutic significance of the results is discussed.     

阿司匹林与糖尿病

阿司匹林是环氧合酶抑制剂,具有抗炎、抗风湿作用。许多研究表明,阿司匹林对缓解糖尿病、预防其心血管并发症起一定作用。其可能的作用机制包括抑制血小板和蛋白质糖基化,通过抑制核因子κB抑制蛋白激酶β(IKKβ)增强胰岛素信号的敏感性,保护胰岛β细胞,从而逆转糖尿病动物的高血糖、高胰岛素血症和脂质代谢紊乱。然而由于糖尿病和高血糖状态下存在代谢紊乱,部分糖尿病患者存在阿司匹林抵抗。阿司匹林的主要不良反应是胃黏膜损伤和胃肠道出血。     

辛伐他汀与阿司匹林联合用药对高血压病患者颈动脉粥样硬化的干预作用

目的探讨高血压病患者在降血压治疗的同时,辛伐他汀和肠溶阿司匹林联合用药对颈动脉粥样硬化和心、脑血管事件的干预作用。方法选择162例高血压病合并颈动脉粥样硬化患者,将其随机分为药物联合干预组和对照组:干预组82例,在降血压治疗的同时应用辛伐他汀(每晚20mg)和肠溶阿司匹林(75mg/d)。对照组80例,仅给予降血压治疗。共随访3年,分别在干预前及干预后第1、2、3年检测颈动脉内-中膜厚度、颈动脉内径、颈动脉内-中膜厚度/颈动脉内径的比值、颈动脉斑块积分及血压、血脂、血小板聚集率和血浆纤维蛋白原等指标。结果干预组在随访后第1年平均颈动脉内-中膜厚度和斑块积分分别为(1.01±0.12)mm、3.8±2.5,与干预前比较差异无显著性(P>0.05),第2、3年分别为(0.80±0.16)mm、2.6±1.6;(0.80±0.20)mm、2.5±1.2,与干预前比较明显降低(P<0.01)。颈动脉内-中膜厚度/内径比值在干预后也明显降低。随访结束时,干预组心、脑血管病的发生率分别为10.90%和4.87%,与对照组相比明显降低(P<0.05)。结论在有效降血压的同时,给予辛伐他汀和肠溶阿司匹林联合用药,能延缓和逆转高血压病患者颈动脉粥样硬化的进展,对心、脑血管事件的发生有很好的预防作用。     

Heart rate reduction with ivabradine prevents thyroid hormone-induced cardiac remodeling in rat

Ivabradine slows the heart rate (HR) by selectively inhibiting the I(f) current in the sinus node without a negative inotropic effect. We aimed to investigate the effects of ivabradine on thyroid hormone-induced left ventricular (LV) remodeling and ion channel activity in rats. Thirty Sprague–Dawley rats were randomly selected into the groups of control, injection of l-thyroxine (T₄, 100 μg/kg/day), and injection of l-thyroxine with ivabradine (T₄-Iva, T₄ + 10 mg/kg/day). Circumferential (S _circ), radial (S _rad), and longitudinal (S _long) strains were assessed by speckle tracking echocardiography (STE). Myocardial width and fibrosis were assessed from histological LV cross sections, and electrophysiological analysis was done by patch clamp method. In comparison with the control group, the T₄ group showed significantly increased HR and LV end-systolic diameter (LVESD), reduced S _circ (?16.04 ± 3.95 vs. ?7.84 ± 2.98 %, p < 0.001), S _rad (20.94 ± 3.81 vs. 40.57 ± 6.70 %, p < 0.001), and S _long (?15.26 ± 5.15 vs. ?23.83 ± 5.19 %, p < 0.001), despite the 59.5 % increase of average I _Ca,L density at 0 mV (13.4 ± 1.2 pA/pF) compared to control group (8.4 ± 0.8 pA/pF). Treatment with ivabradine significantly reduced HR and LVESD, improved SR_circ, S _long and SR_long in the T₄ group, and the average I _Ca,L density at 0 mV in T₄-Iva groups (9.9 ± 1.6 pA/pF) was restored to the control level. Morphologically, the T₄ group showed significantly increased cardiomyocyte width (25.3 ± 1.89 vs. 18.90 ± 1.14 μm in control, p < 0.001) and fibrosis, which were not significantly changed by ivabradine. In conclusion, selective HR reduction by ivabradine attenuates thyroid hormone-induced reduction of myocardial deformation and altered intracellular Ca²⁺ handling without modification of the myocyte hypertrophy with fibrosis in rats.     

卡托普利相关的咳嗽及阿司匹林对其影响

目的　观察卡托普利相关的咳嗽特点及应用卡托普利和氯沙坦时血栓素 B2(TXB2)和6-酮前列环素F1α(6 -Keto -PGF1α)的变化,并对卡托普利咳嗽者换用氯沙坦或加用阿司匹林后咳嗽特点进行分析。方法　心血管病患者450例随机分为卡托普利组和氯沙坦组(卡托普利组 300 例,氯沙坦组150例)。观察两组咳嗽发生率及咳嗽特点,对56例卡托普利咳嗽者 28 例改服氯沙坦,另 28例加用阿司匹林。应用放射免疫分析法检测用药前后血、尿 TXB2和 6- Keto- PGF1α含量。结果　(1)咳嗽发生率在卡托普利组18. 67%,氯沙坦组 1.33%。卡托普利组咳嗽者 28 例换用氯沙坦后 27 例咳嗽停止;另28例加用阿司匹林300 mg/d后,21 43%咳嗽消失,25%咳嗽减轻。(2)卡托普利咳嗽者血TXB2升高(101. 23±28. 46 vs 89. 57±30. 13) pg/mL,血、尿中 6 -Keto- PGF1α下降(血:98 .78±34 .01 vs 112 .30±31 .82;尿:178. 18±37. 36 vs 192 .46±40 .39)pg/mL,TXB2/6 Keto PGF1α比值增加(血:1. 48±0.46 vs 1.31±0 .42;尿:0. 63±0.21 vs 0. 55±0. 18),(以上 P均<0. 05)。(3)卡托普利咳嗽者,TXB2/6 Keto PGF1α比值在改服氯沙坦(血:1 .48±0 .37 vs 1. 63±0 .33;尿: 0 .61±0 32vs1 03±0 21)pg/mL或加阿司匹林(血:1 41±0 .24 vs 1 .69±0 .     

Urinary free cortisol is not a biochemical marker of hypertension

BACKGROUND: Increasing evidence suggests that glucocorticoids might play a role in blood pressure (BP) control. These reports show that cortisol (F) can increase the BP acting on the mineralocorticoid receptor in kidney, brain, heart, and blood vessel. The aim of this study was to evaluate the effects of F in the renal salt and water reabsorption in essential hypertensive patients (EH). METHODS: We studied 364 EH and 102 normotensive (NT) subjects. We obtained 24-h urine to measure urinary free cortisol (UFF) and creatinine (Cr). The upper limit of the UFF/Cr ratio was calculated from NT subjects. Patients with a high UFF/Cr ratio underwent dexamethasone suppression test (DST). Blood samples were used to determine plasma renin activity (PRA), aldosterone (SA), F, cortisone (E), urinary Na/K ratios, adrenocorticotrophic hormone levels, and also to purify lymphocytes for binding assays and genetic analysis. RESULTS: In EH subjects the UFF/Cr and F/E ratios were higher than in normotensives (48.3 microg/g [33.6 to 57.5 microg/g] v 32.6 microg/g [5.6 to 34.6 microg/g], P < .001 and 3.9 microg/g [3.3 to 4.8 microg/g] v 3.0 microg/g [2.4 to 3.6 microg/g], respectively), whereas the SA and PRA levels were similar. The upper limit value for UFF/Cr was set at 51.6 microg/g. The EH patients with high UFF/Cr (123/364, 34%) had lower PRA (1.5 ng/mL/h [0.9 to 2.5 ng/mL/h] v 2.0 ng/mL/h [1.1 to 3.0 ng/mL/h], P = .012, SA levels (7.1 ng/dL [4.1 to 10.5 ng/dL] v 7.9 ng/dL [5.2 to 11.0 ng/dL], P = .045) and Na/K ratios (3.6 [2.8 to 5.8] v 4.0 [3.1 to 6.6], P < or = .05) than those with normal UFF/Cr ratios. We found a slight negative relationship between UFF/Cr and PRA (r = -0.117, P = .031), SA (r = -0.096, P = .058) and Na/K ratios (r = 0.176, P = .059). We did not find significant differences in serum F/E ratios between EH patients with high or normal UFF/Cr (3.9 [3.3 to 5.1] v 3.8 [3.2 to 4.7], P = not significant [NS]) or a correlation between F/E ratio and UFF excretion (r = 0.032, P = NS). We did not find any association between UFF/Cr with systolic BP (P = .349) or diastolic BP (P = .895). Forty EH with the highest UFF/Cr values underwent the DST, which resulted in suppressed serum F in all of them. Binding assays in 4 of 13 EH with the highest UFF/Cr ratio showed a low affinity to dexamethasone (K(d) 13.7 to 33.0 nmol/L). The polymerase chain reaction (PCR) amplification of the GR gene (ligand-binding domain exons) did not show mutations or gross alterations. CONCLUSIONS: We found an EH subpopulation with abnormally high values of UFF but evidence of only a minor mineralocorticoid action, which was not directly related to the BP elevation, suggesting that another alternative mechanism could be triggering the F-induced hypertension. The origin of hypercortisoluria was not elucidated; however, a subtle glucocorticoid resistance was found in some cases.