[Expression and significance of Clara cell secretory protein in injury lungs of Kunming mice after n-hexane long-term inhalation].

OBJECTIVE: To observe the expression of Clara cell secretory protein(CCSP) in the Kunming mouse model of n-hexane long-term inhalation, and to discuss the functions of Clara cell in injury lung induced by n-hexane. METHODS: 24 healthy mice were randomly divided into 4 groups: one control group and three n-hexane groups (4 w, 8 w and 12 w), 6 each group. Primary concentration of n-hexane was 17.6 g/m3, 8 hours per day, 6 d per week. After inhalation, n-hexane concentration of blood from celiac artery was detected. The lungs were embedded with paraffin and HE staining in the routine. The ratio of Clara cells with CCSP reaction in bronchiole and the number of macrophage cells with lysozyme reaction were determined by immuno-histochemistry. RESULTS: In the poisoning groups, the average n-hexane concentration of blood was significantly higher than that of the control group (P < 0.01). There were apparent pathologic damages in lungs of the poisoning mice. In poisoning 4 w, 8 w and 12 w groups, the ratio of Clara cells was significantly decreased [(73.33 +/- 4.21)%, (60.98 +/- 4.94)%, (34.04 +/- 2.33)% in terminal bronchiole, and (75.44 +/- 7.91)%, (58.54 +/- 4.86)%, (33.35 +/- 2.67)% in respiratory bronchiole] as compared with the control mice [(80.26 +/- 6.43)% and (81.74 +/- 7.75)%, P < 0.05 or P < 0.01], meanwhile the numbers of macrophage cells were gradually increased [(21.39 +/- 7.41), (28.54 +/- 10.73), (48.97 +/- 19.55) per microscopic field at 200x] in poisoning mice than those in control mice [(7.84 +/- 3.12) per microscopic field at 200x, P < 0.05 or P < 0.01]. CONCLUSION: In injury lungs after n-hexane inhalation, Clara cells are the target cells of n-hexane toxicity effect. Clara cells play an extensive protective role in lung inflammation.

[Effects of atenolol and diltiazem-SR on quality of life in the hypertensive patients].

OBJECTIVE: To compare the efficacy of atenolol and diltiazem-SR and the effects on the quality of life in hypertensive patients. METHODS: Seventy-three patients with mild to moderate hypertension (DBP 90 - 109 mmHg) were allocated randomly to be administered with atenolol 25 mg/d (group A, n=37) and diltiazem-SR 90 mg/d (group B, n=36) for eight weeks. The changes of heart rate, office blood pressure(OBP), ambulatory blood pressure(ABP) and the quality of life were compared before and after treatment. RESULTS: Heart rate, OBP and ABP decreased after treatment in both groups. The effective rate of blood pressure was 88.2% in group A and 93.8% in group B. Twenty four hour mean daytime and nighttime BP,daytime and nighttime BP loads declined in both groups (P<0.05 - 0.01). The quality of life was significantly increased in group B (P<0.05). Side effects were 21.6% in group A and 11.1% in group B, respectively (P>0.05). CONCLUSION: Atenolol and diltiazem-SR are more effective and tolerant in the treatment of the hypertension. Diltiazem improves the quality of life better than atenolol.

[Different combination of drugs regarding the damage on organs targeting salt sensitivity or non-salt-sensitive hypertension].

OBJECTIVE: To study the damage on organs from salt sensitivity hypertension or non-salt-sensitive hypertension and the selection of drug combination. METHODS: 120 hypertensive patients including 60 cases salt-sensitive (SS) and 60 non-salt-sensitive (NSS) groups were selected in our hospital and their salt load tested. These two groups were randomly divided into two groups, each group with 30 patients, one was given felodipine and perindopril and the others were given indapamide sustained release tablets and perindopril to facilitate the 12-week treatment. Before and after the treatment, patients were tested for physiological indicators, such as sitting blood pressure, 24-hour ambulatory blood pressure, insulin resistance index, comparing changes of various sub-index etc. RESULTS: Significantly different were seen in indices as fasting blood glucose and serum creatinine (P < 0.01), fasting insulin, left ventricular mass index, urinary albumin, body mass index, insulin resistance indices, while between the SS group and the NSS group (P < 0.05). In the SS group, when patients with various sub-indicators were using perindopril combined with indapamide treatment, the related detected indicators tended to be normal and with statistically significant differences (P < 0.05). In the NSS group, those related indexes also tended to be more normal when using felodipine combined with perindopril. However, there were statistically significant differences between the two groups (P < 0.05). CONCLUSION: On SS hypertensive patients with target organ damages, perindopril and indapamide seemed to be more effective in NSS patients, indicating that the use of perindopril and felodipine combination, seemed to be more suitable.

The elevated serum S100A8/A9 during acute myocardial infarction is not of cardiac myocyte origin.

Overproduction of circulating S100A8/A9 occurs in patients following acute myocardial infarction (AMI). It remains unclear whether ischemia insult per se induces S100A8 and S100A9 expression in cardiac myocytes or even whether the cardiac myocytes participate as a source of these proteins. In this study, western blot analysis and quantitative real-time reverse transcription polymerase chain reaction were used to test samples obtained from isolated spontaneously hypertensive rat hearts and Wistar-Kyoto rat hearts subjected to global normothermic ischemia and from neonatal Wistar rat cardiac myocytes undergoing hypoxia. Ischemia did not increase the expression of S100A8 and S100A9 proteins and mRNA in the myocardium either from the spontaneously hypertensive rat hearts or the Wistar-Kyoto rat hearts. In addition, the levels of S100A8 and S100A9 proteins were unchanged in the neonatal rat cardiac myocytes undergoing hypoxia. However, both ischemia and hypoxia activated NF-kappaB in ischemic myocardium and in hypoxic cardiac cells in a time-dependent manner. The results suggest that the increased serum S100A8/A9 concentrations following AMI were not of cardiac myocyte origin.

Proteasome inhibitor MG132 suppresses number and function of endothelial progenitor cells: involvement of nitric oxide synthase inhibition.

The aim of this study was to determine whether proteasome inhibitor MG132 treatment has any effect on endothelial progenitor cells (EPCs). Total mononuclear cells (MNCs) were isolated from peripheral blood by Ficoll density gradient centrifugation. EPCs were identified as adherent cells double positive for DiLDL-up-take and lectin binding by direct fluorescent demonstrated under a laser scanning confocal microscope. After 7 days in culture, EPCs were stimulated with proteasome inhibitor MG132 in series of final concentrations of 20, 50, 100, 200 nmol/l for 12, 24, 48 h. Cell proliferation and apoptosis were determined, respectively, by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, annexin V/propidium iodide binding assay. Colony-forming capacity was performed by colony assay. EPCs adhesion and migration were assayed with adhesion assay and transwell migration assay, respectively. The expression of endothelial nitric oxide synthase (eNOS) was assayed by Western blot analysis, while nitric oxide (NO) generation was detected using the Griess method. It was found that proteasome inhibitor MG132 decreased the number of EPCs and EPC colonies, increased EPC apoptosis, decreased EPC proliferative, adhesive, migration capacity and eNOS/NO production in a concentration- and time-dependent manner. These data indicate that proteasome inhibitor MG132 suppresses the number and function of EPCs, and these actions may involve decreased eNOS/NO production in the EPCs.

Captopril administered at night restores the diurnal blood pressure rhythm in adequately controlled, nondipping hypertensives.

The aim of our study was to evaluate whether captopril administered at night, can shift the circadian blood pressure (BP) from a nondipper to a dipper pattern in adequately controlled hypertensive patients, who continued their antihypertensive therapy. In a prospective, randomized, double blind, placebo-controlled designed study, we enrolled 121 treated, adequately controlled nondipping hypertensive patients. All patients were randomly assigned to 12.5 mg captopril or placebo treatment administered at night. In case of nondippers, the dosage of captopril or placebo was doubled after two weeks of treatment, while for dippers antihypertensive regimens were not changed. After another two weeks, all patients underwent ambulatory BP monitoring. Our results show that at the end of the active treatment period, the prevalence of a dipping diurnal BP pattern in the captopril group (70%) was significantly higher than that in the placebo group (9.8%, P < 0.001). Nighttime BP, night/day BP ratio, nighttime BP load and 24-h systolic BP were significantly lower after 4 weeks nighttime captopril treatment compared to baseline. In conclusion, the present study demonstrates for the first time that captopril administered at night can restore the diurnal BP rhythm and decrease the elevated night/day BP ratio in appropriately controlled, nondipper hypertensive patients. These results were mainly due to the decrease of nighttime BP.

Differential effects of morning or evening dosing of amlodipine on circadian blood pressure and heart rate.

OBJECTIVES: To compare the effects of morning and evening dosing of amlodipine on both circadian blood pressure (BP) and heart rate (HR) in mild-to-moderate essential hypertension. DESIGN: A perspective, double-blind, randomized, crossover design with dose titration. PATIENTS AND METHODS: Sixty-two patients recruited in the study were aged 21-77 years and had mild-to-moderate essential hypertension. At the end of a 2-week single-blind, placebo run-in period, eligible patients were randomly assigned to morning (7 AM) and evening (9 PM) amlodipine treatment. The initial dose was 5 mg. After 2 weeks of double-blind therapy, patients with a seated diastolic blood pressure > or =90 mm Hg had their doses titrated upward to 10 mg, while the other patients remained on their original 5 mg doses for another 4 weeks period, than crossover to the alternate dosing regimen for 6 additional weeks. The 24-h ambulatory monitoring was performed at baseline and at 6 and 12 weeks after randomization. RESULTS: 24-h diastolic BP load (11.0 +/- 17.5% vs. 6.5 +/- 9.1%, P < 0.05) and night-time BP load (28.5 +/- 31.4%/17.7 +/- 28.2% vs. 20.0 +/- 27.9%/9.2 +/- 17.8%, P < 0.05/0.05) were significantly greater with evening dosing compared with morning dosing. Nocturnal fall of BP was greater with morning dosing than with evening dosing (9.8 +/- 6.7/7.4 +/- 5.3 vs. 6.7 +/- 6.6/5.4 +/- 5.4 mm Hg, P < 0.01/0.05). Percentage of nocturnal BP fall was greater with morning dosing versus with evening dosing (7.9 +/- 5.3%/9.6 +/- 6.8% vs. 5.4 +/- 7.0%/7.0 +/- 6.9%, P < 0.01/0.05). CONCLUSIONS: Morning administered amlodipine had a better effect on the circadian BP compared with evening administrated amlodipine in mild-to-moderate essential hypertension.

[Profile on circadian blood pressure and the influencing factors in essential hypertensive patients after treatment].

OBJECTIVE: To explore the circadian blood pressure (BP) profile and its influencing factors in essential hypertensive patients after treatment. METHODS: Cross-sectional surveillance was carried out in essential hypertensive subjects after treatment whose clinic blood pressure had been under control as 140/90 mm Hg (1 mm Hg = 0.133 kPa) for at least one month. All patients underwent a twenty-four-hour ambulatory blood pressure monitoring device (spacelabs 90207). The nocturnal fall of blood pressure (BP) was calculated from (daytime mean BP-night-time mean BP)/daytime BP, while 'daytime' values were recorded between 6 h and 22 h and 'night-time' values between 22 h and 6 h. Non-dippers were defined as those whose nocturnal decrease in mean systolic BP and/or mean diastolic BP was < 10% of the daytime BP. Binary logistic regression analysis was used to evaluate the correlation between circadian blood pressure profile and factors as gender, age, height, body mass index (BMI), family history of premature cardiovascular disease, women under age 65 or men under age 55, smoking habits, grade of hypertension, and strategy of antihypertensive drugs. RESULTS: 208 treated essential hypertensive patients were enrolled in the study. 79 individuals were dippers and 129 were non-dippers. Data from logistic regression analysis showed that four factors as age, premature family history of cardiovascular disease, overweight or obesity, and strategy of antihypertensive drugs were significantly influencing the circadian blood pressure profile in treated hypertensive patients. The incidence of non-dippers in patients of 70 years of age or older and those between 60 and 69 were 3.3 and 2.3 times of those with less than 60 (P = 0.009 and 0.031, respectively). The prevalence of non-dippers in patients with a premature family history of cardiovascular disease was 3.7 times greater than those in subjects without a premature history of cardiovascular disease (P = 0.029). Similarly, the incidence of non-dippers in patients of overweight (24 /= 28) were 3.0 and 4.8 times of those in subjects of normal weight (P = 0.003 and 0.009, respectively). Compared with patients treated with long-acting calcium channel blockers (CCBs), patients treated with angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs) alone had less prevalence of nondippers (OR = 0.139, P = 0.010). Patients treated with joint antihypertensive scheme including ACE inhibitors or ARBs(but not including diuretics) had the tendency of lower incidence of abnormal circadian blood pressure rhythm (OR = 0.453, P = 0.118). Patients treated with joint antihypertensive scheme including diuretics (not including ACE inhibitors or ARBs) and with joint antihypertensive strategy including diuretics and ACE inhibitors or ARBs had lower incidence of nondippers (OR = 0.378 and 0.273, respectively; P = 0.030 and 0.011, respectively). CONCLUSIONS: Approximately 2/3 treated essential hypertensive patients had a non-dipper blood pressure profile. Age, premature family history of cardiovascular disease, overweight/obesity, and antihypertensive drugs strategy were correlated with circadian blood pressure profile. Compared with long-acting CCBs, diuretics, ACE inhibitors or ARBs might be helpful in keeping the circadian blood pressure rhythm at normal range.