双肾双夹肾性高血压大鼠左心室肌球蛋白重链同型异构 …

目的和方法：测定双肾双夹（２Ｋ２Ｃ）肾性高血压大鼠早期,左心室α－肌球蛋白重链（α－ＭＨＣ）和β－肌球蛋白重链（β－ＭＨＣ）ｍＲＮＡ水平的变化。实验分四组：对照组、２Ｋ２Ｃ组、巯甲丙脯酸组、巯甲丙脯酸对照组。术后２４ｈ、３６ｈ、４８ｈ、７２ｈ测动脉血压,提取左心室中样本取８．０μｇ,与＾３２Ｐ标记的α－ＭＨＣ和β－ＭＨＣ ｃＤＮＡ探针作班点杂交。结果：高血压大鼠左心室α－ＭＨＣ ｍＲＡ水平明显降低     

Bradykinin (B2 independent effect of captopril on the development of pressure overload cardiac hypertrophy

Besides the reduction of angiotensin II formation, locally increased kinins may play a role in the cardiovascular action of angiotensin converting enzyme (ACE) inhibitors.To characterize the contribution of bradykinin to the effects of ACE inhibition by captopril on the development of pressure overload hypertrophy, sham-operated rats and rats with ascending aortic constriction were treated with captopril (80 mg/kg/day) or captopril and B₂-kinin receptor antagonist HOE 140 (0.5 mg/kg/day) for 7 weeks. Left ventricular mass and geometry, hydroxyproline concentration and myosin isozymes (marker of a fetal phenotype) were assessed. Rats with aortic constriction exhibited a marked increase in left ventricular weight and diastolic pressure-volume relationship was shifted to smaller volumes. Signs of congestive heart failure were not apparent. The hydroxyproline concentration remained unaltered. However, the proportion of isomyosin V3 was increased (p < 0.05). Administration of captopril reduced (p < 0.05) systolic blood pressure, body and cardiac weight in all treated rats. The reduction of left ventricular weight was disproportionally higher in pressure overloaded rats, thus the relative left ventricular weight decreased by 15% (p < 0.05). Captopril augmented the isomyosin V1 expression (p < 0.05) in sham operated as well as pressure overloaded rats. The isomyosin V1 percentage was inversely related to the relative left ventricular weight. Two different (p < 0.05) correlation lines were detected for untreated and captopril treated rats. None of captopril associated effects were removed by simultaneously administered B₂ kinin receptor antagonist HOE 140.Thus, stimulation of bradykinin B2 receptor appears not to mediate the effects of captopril on cardiac growth and contractile proteins during the development of pressure overload hypertrophy.     

Interactions between the endocrine and immune systems in locusts

Abstract. The prophenoloxidase cascade in the haemolymph of mature adult Locusta migratoria migratorioides (R & F) is activated in response to injection of laminarin, a β‐1,3 glucan. Co‐injection of adipokinetic hormone‐I (Lom‐AKH‐I) and laminarin prolongs the activation of the enzyme in a dose‐dependent manner. However, injections of bacterial lipopolysaccharide (LPS) do not activate prophenoloxidase unless AKH is co‐injected, when there is a dose‐dependent increase in the level of phenoloxidase that persists in the haemolymph for several hours. Even when AKH is co‐injected, the highest levels of phenoloxidase activity are always greater after injection of laminarin than after LPS, and these two immunogens must activate the prophenoloxidase cascade by quite distinct pathways. In the present study, interactions between the endocrine and immune systems were examined with respect to activation of prophenoloxidase and the formation of nodules: injection of LPS induces nodule formation in adult locusts. With LPS from Pseudomonas aeruginosa, nodules form exclusively in dense accumulations in the anterior portion of the abdomen on either side of the dorsal blood vessel associated with the dorsal diaphragm. However, with LPS from Escherichia coli, fewer nodules are formed but with a similar distribution, except that occasionally some nodules are aligned additionally on either side of the ventral nerve cord. Co‐injection of Lom‐AKH‐I with LPS from either bacteria stimulates greater numbers of nodules to be formed. This effect of coinjection of AKH on nodule formation is seen at low doses of hormone with only 0.3 or 0.4 pmol of Lom‐AKH‐1, respectively, increasing the number of nodules by 50%. Injections of octopamine or 5‐hydroxytryptamine do not mimic either of the actions of Lom‐AKH‐I described here. Co‐injection of an angiotensin‐converting enzyme inhibitor, captopril, reduces nodule formation in response to injections of LPS but has no effect on the activation of phenoloxidase. Co‐injection of an inhibitor of eicosanoid synthesis, dexamethasone, with LPS influences nodule formation (with or without AKH) in different ways according to the dose of dexamethasone used, but does not affect activation of prophenoloxidase. Eicosanoid synthesis is important for nodule formation, but not for the activation of the prophenoloxidase cascade in locust haemolymph.     

Probing the interaction of l‐captopril with metallo‐β‐lactamase CcrA by fluorescence spectra and molecular dynamic simulation

Both the molecular recognition and interaction of metallo‐β‐lactamase CcrA with l ‐captopril were studied by the combined use of fluorescence spectra and molecular dynamic simulation. The results showed that the binding constant was 8.89 × 10⁴ L mol^?1 at 296 K. Both Zn1 and Zn2 displayed tetrahedral coordination geometries in the CcrA–Lcap complex, the S atom in l ‐captopril displaced the nucleophilic hydroxide in apo CcrA and occupied the fourth coordination site for each ion, resulting in a competitively inhibited CcrA enzyme. Strong electrostatic interaction between the two zinc ions in CcrA and negatively charged l ‐captopril provided the main driving force for the binding affinity. Through a partly structural transformation from β‐sheet to random coil, loop 1 (residues 24–34) completely opened the binding pocket of CcrA to allow an induced fit of the newly introduced ligand. This study may provide some valuable information for designing and developing a more tightly binding inhibitor to resist superbugs.     

Captopril protects mice bone marrow cells against genotoxicity induced by gamma irradiation

The radioprotective effects of captopril were investigated by using the micronucleus test for anticlastogenic and cell proliferation activity. A single intraperitoneal administration of captopril at doses of 10, 25 and 50 mg/kg 1 h prior to gamma irradiation (2 Gy) reduced the frequencies of micronuleated polychromatic erythrocytes (MnPCEs). All three doses of captopril significantly reduced the frequencies of MnPCEs and increased polychromatic erythrocytes (PCE)/PCE+NCE (normochromatic erythrocyte) ratio in mice bone marrow compared to the non-drug-treated irradiated control (p < 0.001). The optimum dose for protection in mouse was 10 mg/kg to protect mice bone marrow 2.18-fold against the clastogenic effects of gamma-irradiation with respect to the non-drug-treated irradiated control. There was a drug dose-response effect of captopril in increasing the PCE/PCE+NCE ratio in bone marrow cells. The maximum protective effect of captopril was at a dose of 25 mg/kg for increasing the PCE/PCE + NCE ratio. Captopril exhibited concentration-dependent antioxidant activity, scavenging > 96% of the 1,1-diphenyl-2-picryl hydrazyl free radicals when used at a concentration of 0.2 mM. In this study captopril reduced lipid peroxidation induced by hydrogen peroxide in mice liver. It appears that captopril, due to its free radical scavenging properties, protects mice bone marrow cells from radiation-induced DNA damage and genotoxicity.     

Seated Saline Suppression Test Is Comparable With Captopril Challenge Test for the Diagnosis of Primary Aldosteronism: A Prospective Study

ObjectiveThe saline suppression test (SST) and captopril challenge test (CCT) are commonly used confirmatory tests for primary aldosteronism (PA). Seated SST (SSST) has been reported to be superior to recumbent SST. Whether SSST is better than CCT remains unclear. We aimed to compare the diagnostic accuracy of SSST and CCT in a prospective study.MethodsHypertensive patients at a high risk of PA were consecutively included. Patients with an aldosterone-renin ratio of ≥1.0 ng/dL/μIU/mL were asked to complete SSST, CCT, and the fludrocortisone suppression test (FST). Using FST as a reference standard (plasma aldosterone concentration [PAC] post FST ≥ 6.0 ng/dL), area under the receiver-operating characteristic curve (AUC), sensitivity, and specificity of SSST and CCT were calculated, and multiple regression analyses were performed to identify potential factors leading to false diagnosis.ResultsA total of 196 patients diagnosed with PA and 73 with essential hypertension completed the study. Using PAC post SSST and PAC post CCT to confirm PA, SSST and CCT had comparable AUCs (AUC_SSST 0.87 [95% CI 0.82-0.91] vs AUC_CCT 0.88 [0.83-0.95], P = .646). When PAC post SSST and post CCT were set at 8.5 and 11 ng/dL, respectively, the sensitivity and specificity of SSST (0.72 [0.65, 0.78] and 0.86 [0.76, 0.93]) and CCT (0.73 [0.67, 0.80] and 0.85 [0.75, 0.92]) were not significantly different. In the multiple regression analyses, 1-SD increment of sodium intake resulted in a 40% lower risk of false diagnosis with SSST.ConclusionSSST and CCT have comparable diagnostic accuracy. Insufficient sodium intake decreases the diagnostic efficiency of SSST but not of CCT. Since CCT is simpler and cheaper, it is preferred over SSST.     

Prevalence,Subtype Classification,and Outcomes of Treatment of Primary Aldosteronism: A Prospective Study in China

ObjectiveTo investigate the prevalence of primary aldosteronism (PA) among participants with hypertension, evaluate the concordance of PA classification between adrenal computed tomography and adrenal venous sampling, and compare the outcomes of surgery and medication for unilateral PA.MethodsA prospective study was conducted among all inpatients with hypertension (n = 7594) at the National Center for Cardiovascular Diseases, China, from May 2016 to April 2018.ResultsOf the 7594 participants, 8.12% (n = 617) with plasma aldosterone-renin ratio ≥3.7 were possible PA cases. Three hundred sixty-seven cases with plasma aldosterone-renin ratio ≥3.7 and plasma aldosterone concentration ≥10 ng/dL were confirmed using the recumbent saline infusion test (69.20%, 182 of 263) or the captopril challenge test (66.5%, 69 of 104, P > .05). The prevalence of PA was 3.31% (n = 251). Of the 251 patients with PA, all of them had multiple comorbidities, and 49.40% (n = 124) had spontaneous hypokalemia. The concordance of PA classification between adrenal computed tomography and adrenal venous sampling was only 47.11%. The patients’ blood pressure declined to normal ranges in the adrenalectomy (85.71%, 30 of 35) and spironolactone (63.04%; 29 of 46) groups (P < .05). Furthermore, hypokalemia was normalized in the adrenalectomy (100.00%; 26 of 26) and spironolactone (94.74%; 18 of 19) groups.ConclusionIt is necessary to incorporate PA screening into routine practice for those with hypertension in the Chinese population. This will assist in ensuring that the best therapeutic schedule based on PA subtypes is devised. Additionally, as a result, it may contribute to restoring the blood pressure levels and reducing the prevalence of comorbidities in these patients with PA.