BACKGROUND: Bevantolol HCl was developed as the first antihypertensive agent that has selective beta1 and alpha1 blocking effects with an additional calcium antagonistic activity. It's expected that antihypertensive effect is comparable to other beta-blockers without any significant adverse effect on lipid and glucose metabolism observed in other drugs, and It has less negative inotropic effect due to peripheral vasodilatation mediated through alpha1 and calcium channel blocking effects. To evaluate the antihypertensive effect and safety of bevantolol HCl, we investigated 73 patients with mild to moderately severe essential hypertension. METHODS: Patients who showed either systolic blood pressure 150-209 mmHg or diastolic pressure 95-119 mmHg, were enrolled in this study. Following placebo period of 2weeks, bevantolol HCl was administered in daily dose of 100-200 mg for 12 weeks. RESULTS: Of the 73 patients, 55 patients who were able to receive bevantolol HCl were observed for the safety and 45 patients who completed this study were evaluated for the antihypertensive effect of the drug. 1) Antihypertensive effect: The mean systolic and diastolic blood pressure significantly decreased from 156.7+/-11.7 mmHg to 144.0+/-16.7 mmHg and from 101.6+/-6.4 mmHg to 93.2+/-9.7 mmHg in two weeks of observation in 37/45 patients (82.2%) and was consistently effective for 12 weeks (p<0.01). Blood pressure under 139/89 mmHg was achieved in 20 out of 45 patients (44.4%). The heart rate also declined from 74.9+/-10.5/min to 69.1+/-14.2/min and the effect lasted for 12 weeks (p<0.01). 2) Safety: Mild adverse effects were observed in 27 out of 55 patients. Only one patient developed a significant bradycardia with heart rate of 40/min, which required withdrawal of the drug. No significant changes in the lipid profiles were observed. CONCLUSION: Bevantolol HCl is highly effective and generally well tolerated with an acceptable safety profile in patients with mild to moderately severe essential hypertension.
Blood Pressure ; Bradycardia ; Calcium ; Calcium Channels ; Glucose ; Heart Rate ; Humans ; Hypertension* ; Metabolism ; Vasodilation

BACKGROUNDSerum osteoprotegerin (OPG) and matrix metalloproteinase-2 (MMP-2) have been shown to play a role in bone metabolism by degrading the bone matrix. The present study was undertaken to compare OPG and MMP-2 with bone mineral density and three markers (alkaline phosphatase (AKP), calcium and phosphorus) in postmenopausal women in Wuhan.

METHODSSerum OPG, MMP-2, and AKP of 78 Chinese postmenopausal women aged 48 to 65 were measured using enzyme-linked immunosorbent assay (ELISA). Bone mineral density was measured with dual energy X-ray absorptiometry (DEXA), and serum calcium and phosphorus were measured by auto biochemical analysis.

RESULTSSerum OPG and MMP-2 concentrations were significantly higher in postmenopausal women with osteoporosis ((127.6 +/- 6.3) ng/L; (1388 +/- 121) microg/L)) than those in age-matched normal controls ((72.3 +/- 2.4) ng/L; (1126 +/- 141) microg/L, P < 0.01). Negative relationships were found between serum OPG, MMP-2 levels and bone mineral density in osteoporotic women. Adjusted by age and body mass index (BMI), the correlation of MMP-2 with bone mineral density of the neck of the femur disappeared. In osteoporotic women, negative correlations between OPG, MMP-2 levels and serum calcium were found (r = -0.216; r = -0.269, P < 0.05), but positive correlations between OPG and serum AKP, serum phosphorus (r = 0.235; r = 0.124, P < 0.05).

CONCLUSIONSSignificant correlations exist between serum OPG, MMP-2 levels and bone metabolism in high bone turnover of postmenopausal osteoporotic women. The concentrations of serum OPG and MMP-2 increase possibly as a concomitant event in the high bone turnover state, such as postmenopausal osteoporosis. Therefore serum OPG and MMP-2 could be used as indicators for the bone metabolism in postmenopausal osteoporotic women.

Aged ; Bone Density ; Bone and Bones ; metabolism ; Calcium ; blood ; Female ; Humans ; Matrix Metalloproteinase 2 ; blood ; Middle Aged ; Osteoprotegerin ; blood ; Postmenopause ; metabolism

Blood Platelets ; drug effects ; metabolism ; Calcium ; blood ; Deoxycholic Acid ; pharmacology ; Humans ; Quinazolines ; pharmacology ; Quinazolinones

OBJECTIVETo determine the expressions of ryanodine receptor type 1 (RyR1) and Cav1.3 L-type calcium channel (Cav1.3) in the vaginal smooth muscle cells of castrated rats and investigate the correlation of RyR1 and Cav1.3 with estrogen in female sexual dysfunction.

METHODSForty female SD rats of 8 weeks were randomly divided into Groups A (2-week sham operation), B (4-week sham operation), C (2-week castration) and D (4-week castration). Two and 4 weeks after surgery, the serum estradiol level was determined with the automated immunochemiluminescence system and the expressions of RyR1 and Cav1.3 in the vaginal smooth muscle were detected by immunohistochemistry and RT-PCR. Gray scale ratio was used to represent the mRNA expression levels of RyR1 and Car1.3, and the optical density value to denote their protein expression levels.

RESULTSSerum estradiol was significantly decreased in Group C ([0.210 +/- 0.026] nmol/L) as compared with A ([0.505 +/- 0.053] nmol/L) (P < 0.01), and so was it in Group D ([0.130 +/- 0.031] nmol/L) in comparison with B ([0.476 +/- 0.058] nmol/L) (P < 0.01). RyR1 and Cav1.3 were expressed in all groups. The mRNA expressions of RyR1 and Cav1.3 were significantly reduced in Group C (0. 680 +/- 0.073 and 0.580 +/- 0.043) as compared with A (0.950 +/- 0.064 and 0.870 +/- 0.019) (P < 0.01), as well as in Group D (0.220 +/- 0.032 and 0.190 +/- 0.020) in comparison with B (0.890 +/- 0.072 and 0.820 +/- 0.021) (P < 0.01). The protein expressions of RyR1 and Cav1.3 were significantly down-regulated in Group C (96.67 +/- 7.75 and 87.97 +/- 6.96) as compared with A (123.69 +/- 10.66 and 106.46 +/- 8.04) (P < 0.01), and so were they in D (86.45 +/- 8.16 and 69.43 +/- 8.30) in comparison with B (109.31 +/- 9.87 and 97.38 +/- 7.56) (P < 0.01).

CONCLUSIONBoth RyR1 and Cav1.3 were expressed in the vaginal smooth muscle cells of the rats, and estrogen might be involved in the regulation of female sexual reaction by acting on the expressions of RyR1 and Cav1.3.

Animals ; Calcium Channels ; metabolism ; Estrogens ; blood ; Female ; Myocytes, Smooth Muscle ; metabolism ; Ovariectomy ; Rats ; Rats, Sprague-Dawley ; Ryanodine Receptor Calcium Release Channel ; metabolism ; Vagina ; cytology

The effects of hepatic ischemia/reperfusion (1/R) injuries on hepatocellular viability and store-operated calcium current (Isoc) in isolated rat hepatocytes and the effects of 2-APB on store-operated calcium current (Isoc) in isolated rat hepatocytes after hepatic ischemia/reperfusion injuries were studied. Hepatic ischemia and reperfusion injury model was established and whole cell patch-clamp techniques were used to investigate the effects of 2-APB on Isoc. The results showed that ischemia/reperfusion injuries could significantly reduce hepatocellular viability and further increase Isoc in hepatocytes and 2-APB (20, 40, 60, 80, 100 micromol/L,) produced a concentration-dependent decrease of Isoc with IC50 value of 64. 63 +/- 10.56 micromol/L, (n = 8). It was concluded that ischemia/reperfusion injuries could reduce hepatocellular viability, probably through increased Isoc in hepatocytes and 2-APB had a protective effect on ischemia/reperfusion-induced liver injury, probably though inhibiting Isoc.
Boron Compounds/*pharmacology ; Calcium Channel Blockers/*pharmacology ; Calcium Channels/drug effects ; Cell Separation ; Hepatocytes/metabolism ; Liver/*blood supply ; Liver/metabolism ; Rats, Sprague-Dawley ; Reperfusion Injury/*metabolism

In the study, the inhibitory effect of epigallocatechin gallate (EGCG) on Calcium oxalate nephrolithiasis and its possible mechanism were investigated. The rat Calcium oxalate nephrolithiasis model was induced through the combined oral administration of ethylene glycol and ammonium chloride, which was intervened with EGCG. Rat blood samples were collected to detect blood creatinine (Cr), blood urea nitrogen (BUN) and blood calcium. Rat urine samples were collected to observe and compare 24-hour urine volume, oxalic acid (Ox) and calcium in urine. Renal samples were collected to prepare tissue slices and observe the pathological changes in Calcium oxalate nephrolithiasis. The expression of osteopontin (OPN) in renal tissues was evaluated by Real-time PCR and Western blot. According to the results, compared with normal rats, rats in the nephrolithiasis model showed significant increases in Cr, BUN, urine Calcium, urine Ox and renal OPN expression (P < 0.05), but obvious decrease in 24-hour urine volume (P < 0.05); Compared with rats with nephrolithiasis, those processed with EGCG revealed remarkable declines in Cr, BUN, urine Calcium and urine Ox (P < 0.05), with significant rise in 24-hour urine volume (P < 0.05) in a concentration-dependent manner. Additionally, compared with the control group, nephrolithiasis rats showed significant pathological changes in Calcium oxalate calculus. After ECCG treatment, the renal pathological changes and OPN expression attenuated significantly in a concentration-dependent manner. The results showed that EGCG inhibits the formation of calcium oxalate nephrolithiasis in rats and shows a notable protective effect on renal functions.
Animals ; Blood Urea Nitrogen ; Calcium ; blood ; Calcium Oxalate ; metabolism ; Catechin ; administration & dosage ; analogs & derivatives ; Creatinine ; blood ; Disease Models, Animal ; Humans ; Kidney ; drug effects ; metabolism ; Male ; Nephrolithiasis ; blood ; drug therapy ; genetics ; Osteopontin ; genetics ; metabolism ; Rats ; Rats, Wistar

OBJECTIVETo study the effect of different extracts of Alisma orientalis on urinary calcium oxalate stone formation in rats and to identify the effective constituents.

METHODDifferent extracts were administered through a stomach tube to rats of different groups with renal calcium oxalate stones induced by ethylene glycol (EG) and ammonium chloride (AC).

RESULTIn the rats administered with ethyl acetate elution of ethyl acetate extract, blood Cr, BUN, renal tissue calcium content, urinary calcium excretion and crystals deposition in renal tissue were significantly lower than those of the stone formation group.

CONCLUSIONThe ethyl acetate elution of ethyl acetate fraction extract of Alisma orientalis can significantly inhibit urinary calcium oxalate stone formation in rats and be the most effective constituent of Alisma orientalis.

Alisma ; chemistry ; Ammonium Chloride ; Animals ; Blood Urea Nitrogen ; Calcium ; metabolism ; Calcium Oxalate ; urine ; Creatinine ; blood ; Drugs, Chinese Herbal ; isolation & purification ; pharmacology ; Ethylene Glycol ; Kidney ; metabolism ; Kidney Calculi ; chemically induced ; metabolism ; prevention & control ; Magnesium ; metabolism ; urine ; Male ; Rats ; Rats, Wistar

OBJECTIVETo observe the role of PKC-potentiated inhibitory protein for protein phosphatase 1 of 17 x 10(3) (CPI-17) in vascular calcium sensitivity regulated by protein kinase Calpha (PKCalpha) and Cepsilon (PKCepsilon) in rats with hemorrhagic shock (HS).

METHODSEight Wistar rats were used to reproduce 2 h HS model. Superior mesenteric artery (SMA) rings from HS rats were randomly divided into 2 h shock group (without treatment), PKCalpha agonist group (with addition of thymelea toxin into the nutrient solution), CPI-17 antibody + PKCalpha agonist group [incubation with thymelea toxin and CPI-17 antibody (1:800)], PKCepsilon agonist group (with addition of carbachol into the nutrient solution), and CPI-17 antibody + PKCepsilon agonist group [incubation with carbachol and CPI-17 antibody (1:800)]. SMA rings from another eight normal rats were used as normal control group. Calcium sensitivity indices (Emax, pD2) of SMA rings were measured by isolated organ perfusion system. Hypoxic VSMCs in primary culture were randomly divided into 2 h hypoxia group, PKCalpha agonist group (with above-mentioned treatment), PKCepsilon agonist group (with above-mentioned treatment), normal VSMCs were used as normal control group. Protein expression and phosphorylation of CPI-17 were measured via Western blot.

RESULTSEmax and pD2 in all the experimental groups were lower than those in normal control group (P < 0.01). Emax in PKCalpha agonist group and PKCepsilon agonist group was increased (5.8 +/- 0.8, 5.8 +/- 0.9 mN, respectively) as compared with that of 2 h shock group (4.1 +/- 0.6 mN, P < 0.01). Protein expression and phosphorylation of CPI-17 in VSMC were significantly decreased in 2 h hypoxia group, compared with those in normal control group (P < 0.05), and those in PKCalpha agonist and PKC agonist groups (P < 0.05 or P < 0.01).

CONCLUSIONSPKCalpha and PKCepsilon may regulate vascular calcium sensitivity through change in protein expression and activity of CPI-17 in HS rats.

Animals ; Calcium ; blood ; pharmacology ; Female ; Male ; Muscle Proteins ; metabolism ; Phosphoproteins ; metabolism ; Phosphorylation ; Protein Kinase C-alpha ; metabolism ; Protein Kinase C-epsilon ; metabolism ; Rats ; Rats, Wistar ; Shock, Hemorrhagic ; metabolism

OBJECTIVETo observe the changes of erythrocyte deformability in rats acclimatized to hypoxia and its molemechanism.

METHODSMale rats were randomly divided into three groups (n = 10): normal control group, acute hypoxia group and hypoxia acclimatization group. Animals were exposed to hypoxia for 0, 1, 28 d, blooded from their hearts after anaesthetized, respectively. Erythrocyte deformability, membrane fluidity, cholesterin and total lipid, lipid components of erythrocyte membrane, erythrocyte membrane ATPase and the concentrations of Na+ and Ca2+ were measured respectively. The two-dimensional electrophoresis maps of the rats erythrocyte membrane protein were achieved. The different protein spots were founded by image master 2D elite and identified by mass spectrum.

RESULTS(1) In acute hypoxia group, the deformability, membrane fluidity, the content of membrane cholesterin and total lipid were declined. The content of phosphatidylserines (PS), sphingomyelin (SM) in erythrocyte membrane lipids were increased, phosphatidylcholine (PC) reduced. The activity of ATP enzymes reduced and the concentration of Na+ and Ca2+ in erythrocyte increased. The two-dimensional electrophoresis maps of the rats erythrocyte membrane protein were achieved. Four of the seven protein spots selected increased and three of them showed no change. (2) In hypoxia acclimatization group, the deformability, membrane fluidity, the content of membrane cholesterin and total lipid were increased than those in acute hypoxia group, similar to normal group. The content of PS, SM in erythrocyte membrane lipids were reduced, PC increased. The activity of ATP enzymes induced and the concentration of Na+ and Ca2+ in erythrocyte increased after hypoxia acclimatization. Four of those protein spots mentioned increase and three declined after hypoxia acclimatization. They were respectively proved by mass spectrum to be alexin binding protein, aquaporin chip, membrane inhibitor reactive lysis, phospholipids scramblase, glucose transferase, aminophospholipid translocases, ATP-dependent floppase, the latter three proteins were associate with the overturning of erythrocyte membrane lipids.

CONCLUSIONAcute hypoxia caused the corresponding damage of erythrocyte deformability, erythrocyte membrane fluidity, erythrocyte membrane proteins erythrocyte expression, the activity of membrane ATPase and the concentration of Na+ and Ca2+ in erythrocyte. The parameters above were improved after hypoxia acclimatization, so hypoxia acclimatization effected positively in the damage to erythrocyte due to acute hypoxia. The three membrane proteins might play important roles in the deformability improved by hypoxia acclimatization, which included phospholipids scramblase, aminophospholipid translocases and ATP-dependent floppase.

Acclimatization ; physiology ; Adenosine Triphosphatases ; metabolism ; Altitude ; Animals ; Calcium ; metabolism ; Erythrocyte Deformability ; physiology ; Erythrocyte Membrane ; metabolism ; Hypoxia ; blood ; physiopathology ; Male ; Membrane Fluidity ; Phospholipid Transfer Proteins ; metabolism ; Rats ; Sodium ; metabolism

OBJECTIVETo study the distribution of gelsolin in human platelet and plasma, and the association with blood-stasis syndrome (BSS) of coronary heart disease (CHD).

METHODSSixty patients with CHD (30 in BSS group and 30 in non-BSS group) and 30 healthy subjects (control group) were included in this study. The classification of the syndrome was based on clinical symptoms and signs. Gelsolin concentration in platelet rich plasma (PRP), platelet poor plasma (PPP), filamentous actin (F-actin) and group-specific component globulin (Gc-globulin) of PPP were determined by enzyme-linked immunosorbent assay (ELISA). The fluorescence intensity of CD62p and cytoplasmic calcium ([Ca(2+)](i)) in human platelets of patients and healthy persons was measured with flow cytometry.

RESULTSCompared with the control group, gelsolin in PRP of the BSS group increased significantly (P<0.01), while that in PPP of the BSS and non-BSS groups decreased markedly (P<0.05), the CD62p, [Ca(2+)](i) of platelet, F-actin, and Gc-globulin of the BSS and non-BSS groups increased significantly (P<0.01). Compared with the non-BSS group, the gelsolin concentration in PRP of BSS group increased significantly (P<0.01), the [Ca(2+)](i) of platelet of the BSS group increased markedly (P<0.01), while the F-actin and Gc-globulin of the BSS group had no statistical defference (P>0.05).

CONCLUSIONSGelsolin concentration in PRP was increased and accompanied by the elevated [Ca(2+)](i) of platelet in CHD with BSS, while gelsolin in PPP were lowered markedly. We speculate that plasma gelsolin may clear F-actin from circulation, thus resulting in depletion of plasma gelsolin significantly. This, in addition to the increased calcium influx of platelets, may lead to the gelsolin abnormal expression on platelets during the process of BSS in CHD. Therefore, platelet gelsolin may serve as a new potential biomarker and a therapeutic target of BSS in CHD.

Actins ; metabolism ; Adult ; Aged ; Blood Platelets ; metabolism ; Calcium ; blood ; Coronary Disease ; blood ; complications ; physiopathology ; Female ; Flow Cytometry ; Gelsolin ; blood ; Globulins ; metabolism ; Hemostasis ; physiology ; Humans ; Male ; Middle Aged ; P-Selectin ; blood ; Syndrome