Pay attention to the clinical value of individualized combination of drugs in the treatment of hypertension / 中国实用内科杂志

Individualized combination medication is an important measure to improve the rate of hypertension control, individualized combination medication is also an important method to protect organs, individualized combination medication is an important measure to reduce drug side effects and improve medication compliance, individualized combination medication is an important way to increase the rate of hypertension control and reduce the mortality and disability of cardiovascular disease. Therefore, it is considered that the emphasis on individualized combination medication for hypertension is an important strategy for prevention and treatment of hypertension.

Status of glucose metabolism in Chinese essential hypertensive patients / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate glucose metabolism status and its relationship with blood pressure, obesity, renal function and cardio-cerebral vascular events in Chinese essential hypertensive patients.</p><p><b>METHODS</b>Essential hypertensive patients without diabetic history were enrolled in this cross-sectional survey. All patients filled in questionnaires and received physical examination and laboratory tests. Oral glucose tolerance test (OGTT, fasting and 2 hours glucose level after drinking the 75 g glucose solution) was performed in patients who signed the informed consent.</p><p><b>RESULTS</b>(1) The control rate of systolic BP was lower in patients with dysglycemia than in patients without dysglycemia (41.0% vs. 46.4%, P = 0.000). (2) The albuminuria detection rate and the abnormal rate of estimated glumerular filtration rate (eGFR) increased significantly with the deterioration of glucose metabolism. (3) Multifactor-analysis showed that abnormal waist circumference, decreased eGFR and presence of albuminuria were independent risk factors for abnormal glucose metabolism. Cardiovascular events was significantly higher in patients with abnormal glucose metabolism than patients with normal glucose metabolism.</p><p><b>CONCLUSION</b>Abnormal glucose metabolism is common in Chinese essential hypertensive patients. When complicated with abnormal glucose metabolism, essential hypertensive patients had poor blood pressure control rate and were related to higher cardiovascular risk.</p>

Arginine vasopressin stimulates proliferation of adult rat cardiac fibroblasts via protein kinase C-extracellular signal-regulated kinase 1/2 pathway / 生理学报

Arginine vasopressin (AVP), a neurohormone and hemodynamic factor implicated in the pathophysiology of hypertension and congestive heart failure, can also act as a growth-stimulating factor. Our previous work demonstrated that AVP is a mitogen for neonatal rat cardiac fibroblasts (CFs). In the present study, we extended our investigations to adult rat CFs to explore whether AVP could induce adult rat CF proliferation and, if so, to identify the mechanism involved. Adult rat CFs were isolated, cultured and subjected to AVP treatment. DNA synthesis and cell cycle distribution were analyzed by [(3)H]-thymidine incorporation and flow cytometry. Cellular extracellular signal-regulated kinase 1/2 (ERK1/2) activity was measured by in vitro kinase assay using myelin basic protein (MBP) as a substrate. Protein expressions of total- and phospho-ERK1/2, p27(Kip1), cyclins D1, A, E were assessed by Western blot. The results showed that AVP stimulated DNA synthesis in adult rat CFs, and the effect was abolished by a V1 receptor antagonist, d(CH(2))(5)[Tyr(2)(Me), Arg(8)]-vasopressin (0.1 μmol/L), but not by a V2 receptor antagonist, desglycinamide-[d(CH(2))(5), D-Ile(2), Ile(4), Arg8]-vasopressin (0.1 μmol/L). AVP induced an activation of ERK1/2, which could be mimicked by the protein kinase C (PKC) activator, phorbol 12-myristate 13-acetate (PMA, 30 nmol/L, 5 min), but abolished by depletion of PKC via chronic PMA incubation (2.5 μmol/L, 24 h). In addition, AVP down-regulated protein expression of p27(Kip1), increased protein expressions of cyclins D1, A and E, and induced cell cycle progression from G(0)/G(1) into S stage. Inhibition of ERK1/2 activation by PD98059 (30 μmol/L) abolished the effect of AVP on DNA synthesis, protein expressions of p27(Kip1), cyclins D1, A and E as well as cell cycle progression. These results suggest that AVP is also a growth factor for adult rat CFs. The mitogenic effect of AVP is mediated via V1 receptors and PKC-ERK1/2 pathway. Moreover, AVP modulates the expressions of cell cycle regulatory proteins p27(Kip1) and cyclins D1, A and E, which lie downstream of ERK1/2 activation, and induces cell cycle progression in adult rat CFs.

The Role of Transforming Growth Factor-?_1 in the Proliferation of Cardiac Fibroblasts Induced by Chymase / 中华高血压杂志

Objective To investigate the effect of chymase on the proliferation of rat cardiac fibroblasts (CFs) and the role of transforming growth factor-?1 (TGF-?_1).Methods Cultured CFs of neonatal SD rats were isolated by trypsinization.Cell number and DNA synthesis were evaluated by MTT assay (A_(490) value) and [~3H]-deoxythy- midine [~3H]-TdR incorporation.The mRNA expression of TGF-?_1 in CFs was determined by RT-PCR.Results Chymase increased CFs numbers and [~3H]-TdR incorporation in a dose-dependent manner.The A_(490) value of CFs stimulated by 15,30 and 60 ng/mL chymase was 0.263?0.033,0.348?0.031 and 0.387?0.026,respectively, which were all significantly higher than that of control (0.201?0.019,P

Inhibitory effect of cyclosporin A on growth and collagen synthesis of rat cardiac fibroblasts induced by arginine vasopressin / 药学学报

<p><b>AIM</b>To investigate the effects of cyclosporin A (CsA) on growth and collagen synthesis of cardiac fibroblasts (CFs) induced by arginine vasopressin (AVP).</p><p><b>METHODS</b>CFs of neonatal Sprague-Dawley rats were isolated by trypsinization and cultured; growth-arrested CFs were stimulated with 1 x 10(-7) mol x L(-1) AVP in the presence or absence of CsA (0.05, 0.5 and 5 micromol x L(-1)). MTT and flow cytometry techniques were adopted to measure cell number and analyze cell cycle respectively. Collagen synthesis was determined by measurement of hydroxyproline content in culture supernatant with colorimetry. Calcineurin activity was estimated by chemiluminescence. Trypan blue staining to test the viability of CFs.</p><p><b>RESULTS</b>0.05, 0.5 and 5 micromol x L(-1) CsA inhibited the increase of CFs number induced by 1 x 10(-7) mol x L(-1) AVP in a dose-dependent manner, with the inhibitory rates by 12%, 24% and 29%, respectively (P < 0.05). Furthermore, cell cycle analysis showed 0.5 micromol x L(-1) CsA decreased the S stage percentage and proliferation index of CFs stimulated by AVP (P < 0.05). In culture medium, the hydroxyproline content induced by AVP decreased by 0.5 and 5 micromol x L(-1) CsA (P < 0.05), with the inhibitory rates of 29% and 33%, respectively. CsA completely inhibited the increment of calcineurin activity induced by AVP (P < 0.01), but CsA itself had no effect on the baseline of calcineurin activity and CFs viability.</p><p><b>CONCLUSION</b>CsA inhibits proliferation and collagen synthesis of CFs by virtue of blocking calcineurin signaling pathway and might provide a novel target for prevention and treatment to cardiac fibrosis.</p>

Effects of simvastatin on DNA synthesis in rat cardiac fibroblasts / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effects of simvastatin (Sim) and the interference by mevalonate (MVA) against its effect on DNA synthesis in rat cardiac fibroblasts (CFs).</p><p><b>METHODS</b>CFs were isolated from neonatal SD rats by trypsin digestion and growth-arrested CFs were stimulated with Sim and/or MVA at varied concentrations for different time lengths, and the DNA synthesis in the cells was measured by (3)H-thymidine ((3)H-TdR) incorporation assay.</p><p><b>RESULTS</b>Sim decreased (3)H-TdR incorporation in the CFs in a concentration-dependent manner, and (3)H-TdR incorporation was significantly lower in cells treated with 1 x 10(-6) and 1 x 10(-5) mol/L Sim (1,175+/-202.66 and 771+/-164.86 cpm/2000 cells, respectively) than in the control cells (1,608+/-204.32 cpm/2000 cells, P<0.01). As the treatment time with 1 x 10(-5) mol/L Sim prolonged (for 6, 12, 18, 24, 36, 42, and 48 h), (3)H-TdR incorporation in CFs decreased gradually, showing an obvious inverse correlation with the treatment time (r=-919, P<0.01). (3)H-TdR incorporation in cells treated with 1 x 10(-6) to 1 x 10(-3) mol/L MVA and 1 x 10(-5) mol/L Sim rose steadily as MVA concentration increased. A significant difference in the incorporation was found between cells treated with both 1 x 10(-4)/1 x 10(-3) mol/L MVA and 1 x 10(-5) mol/L Sim (1,612+/-308.57 and 1,995+/-353.83 cpm/2000 cells, respectively) and the cells with 1 x 10(-5) mol/L Sim treatment alone (P<0.01); difference was also noted between cells treated with 1 x 10(-5) mol/L MVA and the control cells (P<0.05), but treatment with 1 x 10(-6) mol/L MVA did not produce much difference in comparison with the control cells (P>0.05) With the increase of treatment time (for 6, 12, 18, 24, 36, 42, 48 h), 1 x 10(-3) mol/L MVA caused steady increase in (3)H-TdR incorporation in the CFs, showing a significant positive correlation with the treatment time (r=0.968, P<0.01).</p><p><b>CONCLUSION</b>Sim can decrease DNA synthesis in rat CFs and postpone the occurrence of myocardial fibrosis, which can be reversed by MVA.</p>

Arginine vasopressin-induced nitric oxide content changes in cultured cardiac fibroblasts and its relation to nuclear factor-kappaB / 生理学报

To investigate the changes in the nitric oxide (NO) contents, nitric oxide synthase (NOS) activity and inducible nitric oxide (iNOS) mRNA expression in arginine vasopressin (AVP)-induced cardiac fibroblasts (CFs) in vitro and its relation to nuclear factor-kappaB (NF-kappaB), CFs were isolated by trypsin digestion method. Nitric acid reductase method, spectrophotometry, reverse transcription-polymerase chain reaction (RT-PCR), immunofluorescence-interactive laser cytometer techniques and Western blotting were used respectively to detect NO contents, NOS activity, iNOS mRNA expression and the activation of NF-kappaB in CFs. AVP increased NO contents, NOS activity and iNOS mRNA expressions in a concentration-dependent manner; NF-kappaB was activated and mobilized from cytoplasm to nucleus in AVP-induced CFs; PDTC, one of the inhibitors of NF-kappaB, could inhibit aforementioned increments. It is suggested that the increases in NO contents, elevation of NOS activity and increment of iNOS mRNA expression may be mediated through NF-kappaB activation pathway in cultured CFs induced by AVP, and that NF-kappaB is involved in the occurrence and development of myocardial fibrosis.