Biomedical subjects

Zhiming Zhu

Publications and source records attributed to Zhiming Zhu.

13 recordsLinked to original sources

PubMed2006

Association of angiotensin-converting enzyme 2 gene A/G polymorphism and elevated blood pressure in Chinese patients with metabolic syndrome.

To establish whether angiotensin-converting enzyme 2 (ACE2) gene A/G single nucleotide polymorphism is associated with hypertension in Chinese patients with metabolic syndrome. The study was conducted in 353 patients with metabolic syndrome. The alleles of the ACE2 A/G polymorphism, which is located on the X chromosome, were detected using polymerase chain reaction and subsequent cleavage by Alu I restriction endonuclease. G allele frequencies in patients with metabolic syndrome were 36.6% in female subjects and 43.4% in male subjects, respectively. Female patients with metabolic syndrome who carry the GG genotype had a significantly higher diastolic blood pressure compared with other genotypes. Multivariate logistic regression showed that female gender (P = 0.019) and carrying only the G allele (odds ratio 2.83 [95% CI 1.36 to 5.91]; P = 0.005) were significantly associated with increased diastolic blood pressure. It is concluded that the ACE2 A/G polymorphism is associated with hypertension in patients with metabolic syndrome.

Angiotensin-Converting Enzyme 2↗

PubMed2006

Transient receptor potential channels in essential hypertension.

OBJECTIVE: The role of nonselective cation channels of the transient receptor potential channel (TRPC) family in essential hypertension has not yet been investigated. METHODS: We studied TRPCs in 51 patients with essential hypertension and 51 age-matched and sex-matched normotensive control subjects. Calcium and gadolinium influx into human monocytes was determined using the fluorescent dye technique. TRPC expression was measured using reverse transcriptase-polymerase chain reaction and in-cell western assay. Gene silencing by small interfering RNA for specific TRPC knockdown was also performed. RESULTS: We observed an increased gadolinium/calcium-influx ratio through TRPC in essential hypertensive patients compared with normotensive control subjects [cation influx ratio (mean +/- SEM), 125 +/- 14 versus 80 +/- 7%; each n = 51; P < 0.01], due to an increase of gadolinium influx in hypertensive patients compared with normotensive control subjects (48 +/- 4 versus 36 +/- 3%; each n = 51; P < 0.05). We observed a significant increase of TRPC3 and TRPC5 protein expression in essential hypertensive patients compared with normotensive control subjects (normalized TRPC3 expression, 3.21 +/- 0.59 versus 1.36 +/- 0.07; each n = 20; P < 0.01; normalized TRPC5 expression, 2.10 +/- 0.28 versus 1.40 +/- 0.52; each n = 12; P < 0.05). We used small interfering RNA for knockdown of TRPC5. The thereby reduced channel expression caused a significant attenuation of calcium and gadolinium influx. CONCLUSION: This study points to an important role of TRPCs in essential hypertension.

Aged↗

PubMed2005

GATA4-mediated cardiac hypertrophy induced by d-myo-inositol 1,4,5-tris-phosphate.

We evaluated the effects of d-myo-inositol 1,4,5-tris-phosphate on cardiac hypertrophy. d-myo-inositol 1,4,5-tris-phosphate augmented cardiac hypertrophy as evidenced by its effects on DNA synthesis, protein synthesis, and expression of immediate-early genes c-myc and c-fos, beta-myosin heavy chain, and alpha-actin. The administration of d-myo-inositol 1,4,5-tris-phosphate increased the expression of nuclear factor of activated T-cells and cardiac-restricted zinc finger transcription factor (GATA4). Real-time quantitative RT-PCR showed that d-myo-inositol 1,4,5-tris-phosphate-induced GATA4 mRNA was significantly enhanced even in the presence of the calcineurin inhibitor, cyclosporine A. The effect of d-myo-inositol 1,4,5-tris-phosphate was blocked after inhibition of inositol-trisphosphate receptors but not after inhibition of c-Raf/mitogen-activated protein kinase kinase (MEK)/mitogen-activated protein kinase (ERK) or p38 mitogen-activated protein kinase pathways. The study shows that d-myo-inositol 1,4,5-tris-phosphate-induced cardiac hypertrophy is mediated by GATA4 but independent from the calcineurin pathway.

Animals↗

PubMed2005

Increased transient receptor potential channel TRPC3 expression in spontaneously hypertensive rats.

BACKGROUND: Disturbances in the regulation of cytosolic calcium concentration have been attributed to primary hypertension, but the role of calcium-permeable transient receptor potential canonical channel 3 (TRPC3) has not yet been evaluated in primary hypertension. METHODS: Expression of TRPC3 was determined using in-cell Western assay. Evaluation of RNA interference for the downregulation of a specific gene in cells by small interfering RNA was performed. Measurements of cytosolic calcium were carried out using the fluorescent dye fura2. RESULTS: Expression of TRPC3 was significantly increased in monocytes from spontaneously hypertensive rats (SHR) compared with normotensive Wistar-Kyoto rats (WKY). Transplasmamembrane calcium influx and thapsigargin-induced sustained calcium increase were significantly higher in SHR compared with WKY. In the presence of the TRP channel blocker SKF-96365 these differences were no longer observed. Specific TRPC3-knockdown by transfection of monocytes from SHR with small interfering RNA significantly reduced TRPC3 expression, trans-plasma membrane calcium influx, and thapsigargin-induced sustained calcium increase. CONCLUSIONS: This study shows, for the first time, increased TRPC3 channel expression and increased TRPC3-related calcium influx in SHR.

Animals↗

PubMed2004

Thiazide-like diuretics attenuate agonist-induced vasoconstriction by calcium desensitization linked to Rho kinase.

Lowering blood pressure using thiazide-like diuretics, including chlorthalidone and hydrochlorothiazide, has been proven to be effective in clinical studies. However, the mechanisms by which thiazide-like diuretics lower blood pressure are still poorly understood. To evaluate whether thiazide-like diuretics cause calcium desensitization in smooth muscle cells, we measured their effects on agonist-induced increase of blood pressure in Wistar rats in vivo and on agonist-induced vasoconstriction of aortic rings, DNA synthesis, and protein synthesis, RhoA, Rho kinase, and intracellular calcium in vascular smooth muscle cells in vitro. Thiazide-like diuretics significantly attenuated angiotensin II-induced or norepinephrine-induced increase of systolic blood pressure in rats. Thiazide-like diuretics inhibited agonist-induced vasoconstriction of aortic rings in a concentration-dependent manner in the presence and absence of endothelium. The inhibitory effects of thiazide-like diuretics were similar to that of the specific Rho kinase inhibitor Y27632. RT-PCR and immunoblotting showed that RhoA and Rho kinase were significantly reduced in vascular smooth muscle cells after administration of thiazide-like diuretics. In contrast, thiazide-like diuretics did not affect protein tyrosine phosphatase-2 (SHP-2) expression. Agonist-induced changes of intracellular calcium were not affected by thiazide-like diuretics. The study indicates that thiazide-like diuretics inhibit agonist-induced vasoconstriction by calcium desensitization in smooth muscle cells linked to the Rho-Rho kinase pathway.

Acute-Phase Proteins↗

PubMed2004

Differentially expressed genes in hypertensive rats developing cerebral ischemia.

The molecular events occurring after cerebral ischemia in hypertension may include de novo expression of numerous genes. Receptor genes are predominantly involved in the process of cell death, neuroprotection and reconstruction after ischemic injury. Ischemic stroke was observed in the non-genetic, non-surgical model of hypertension, the cold-induced hypertensive rat. In hypertensive rats suppression subtractive hybridization analysis was used to identify differentially expressed receptor genes in stroke-tissue compared to normal rat brain. We found 76 genes predominantly expressed in hypertensive rat stroke-tissue. These predominantly expressed genes included genes involved in energy metabolism, signal transduction/cell regulation, and replication/transcription/translation. For example, the T3 receptor alpha was predominantly expressed in stroke-tissue, indicating that regeneration of nerves in stroke tissue may be facilitated by increased T3 receptor alpha expression.

Animals↗

PubMed2004

Effect of sodium on blood pressure, cardiac hypertrophy, and angiotensin receptor expression in rats.

BACKGROUND: Sodium-induced hypertensive cardiac hypertrophy is related to pressure and volume overload. METHODS: Wistar rats were exposed to low and high sodium diet for 8 weeks. Angiotensin II receptor mRNA, abundance of p38 mitogen-activated protein kinase (p38MAPK), vasoconstriction of aortic rings, and angiotensin II-induced calcium increase were investigated. RESULTS: Rats on high sodium diet showed significantly elevated blood pressure. Heart weight, AT1 receptor mRNA in cardiac and aortic tissues, and abundance of p38MAPK were significantly increased in rats on high sodium diet. CONCLUSIONS: Increased AT1 receptor expression and angiotensin II-induced calcium increase are compensatory effects in sodium-induced hypertension.

Animals↗

PubMed2004

Effect of sodium on vasoconstriction and angiotensin II type 1 receptor mRNA expression in cold-induced hypertensive rats.

Angiotensin II and sodium play an important pathogenetic role in several models of hypertension. Now, we investigated the effects of sodium on vasoconstriction and angiotensin II type 1 (AT1) and type 2 (AT2) receptor mRNA expression in aortic vessels from cold-induced hypertensive rats. Wistar rats on low sodium and high sodium diet were exposed to cold-stress for 8 weeks. The effects of angiotensin II infusion on mean arterial blood pressure were investigated in these rats. In addition, angiotensin II induced contraction was measured using aortic rings. Expression of AT1 receptor mRNA and AT2 receptor mRNA was assessed in aortic vessels by reverse transcription polymerase chain reaction. After infusion of angiotensin II mean arterial blood pressure in cold-induced hypertensive rats on high sodium diet was significantly higher compared to cold-induced hypertensive rats on low sodium diet (p < 0.05). Angiotensin II-induced contraction of aortic rings was significantly higher in cold-induced hypertensive rats on high sodium diet compared to cold-induced hypertensive rats on low sodium diet (2.39 +/- 0.03 g vs. 2.21 +/- 0.04 g, n = 12, p < 0.01). Angiotensin AT1 receptor mRNA was significantly higher in cold-induced hypertensive rats on high sodium diet compared to cold-induced hypertensive rats on low sodium diet (p < 0.05). It is concluded that in this nongenetic, nonsurgical animal model of cold-induced hypertension increased vasoconstriction and increased AT1 receptor mRNA expression in aortic vessels are dependent on sodium intake.

Animals↗

PubMed2003

Elevated plasma homocysteine was associated with hemorrhagic and ischemic stroke, but methylenetetrahydrofolate reductase gene C677T polymorphism was a risk factor for thrombotic stroke: a Multicenter Case-Control Study in China.

BACKGROUND AND PURPOSE: It is still controversial whether elevated plasma homocysteine and the C677T polymorphism of methylenetetrahydrofolate reductase (MTHFR) gene are risk factors for stroke. The aim of the present study was to investigate the association between the 2 factors and stroke in Chinese in a large case-control study. METHODS: We recruited 1823 stroke patients (807 cerebral thrombosis, 513 lacunar infarction, 503 intracerebral hemorrhage) and 1832 controls. Total plasma homocysteine was determined by high-performance liquid chromatography. C677T polymorphism was genotyped by polymerase chain reaction and HinfI digestion. RESULTS: Total plasma homocysteine levels were significantly higher in cases than controls (median, 14.7 versus 12.8 micromol/L; P<0.001) and associated with an increased risk of 1.87-fold (95% confidence interval [CI], 1.58 to 2.22) for overall stroke, 1.72-fold (95% CI, 1.39 to 2.12) for cerebral thrombosis, 1.89-fold (95% CI, 1.50 to 2.40) for lacunar infarction, and 1.94-fold (95% CI, 1.48 to 2.55) for intracerebral hemorrhage. The C677T mutation of the MTHFR gene was positively correlated with plasma homocysteine levels in both controls (beta=0.250, P<0.001) and cases (beta=0.272, P<0.001) and more frequently in cases than in controls (47.0% versus 44.2%, P=0.017). The TT genotype was associated with an increased risk for overall stroke (odds ratio, 1.27; 95% CI, 1.04 to 1.56) and thrombotic stroke (odds ratio, 1.37; 95% CI, 1.06 to 1.78). CONCLUSIONS: The C677T polymorphism of the MTHFR gene was associated with increased risk of cerebral thrombotic stroke in Chinese. Total plasma homocysteine was correlated with both ischemic and hemorrhagic stroke, suggesting potential initiation of homocysteine-lowering therapy in this population.

Brain Ischemia↗

PubMed2003

Pentanucleotide TTTTA repeat polymorphism of apolipoprotein(a) gene and plasma lipoprotein(a) are associated with ischemic and hemorrhagic stroke in Chinese: a multicenter case-control study in China.

BACKGROUND AND PURPOSE: It is still inconclusive whether high plasma lipoprotein(a) [Lp(a)] level is a risk factor for stroke. Small sample size and different ethnic groups and methodologies might be contributors to the conflicts in study results. The purpose of the present study was to investigate the association between plasma Lp(a) levels, pentanucleotide TTTTA repeat (PNTR) polymorphism of the apolipoprotein(a) [apo(a)] gene, and Chinese stroke in a case-control study. METHODS: We recruited 1825 cases with stroke (44.3% cerebral atherothrombosis, 28.3% lacunar infarction, and 27.3% intracerebral hemorrhage) and 1817 controls from 7 centers in China. Lp(a) concentrations were quantified by enzyme-linked immunosorbent assay. The PNTR polymorphism of the apo(a) gene was determined by polymerase chain reaction-polyacrylamide gel electrophoresis. Conditional multivariate logistic regression analysis was used to identify independent risk factors for stroke and its subtypes. RESULTS: Lp(a) levels were significantly higher in cases than in controls (median, 28.5 versus 23.1 mg/dL; P<0.001), leading to a 1.97-fold (95% CI, 1.64 to 2.37) increase in risk for overall stroke, 2.0-fold (95% CI, 1.59 to 2.52) increase for atherothrombotic type, 2.05-fold increase (95% CI, 1.59 to 2.63) for lacunar type, and 1.64-fold increase (95% CI, 1.21 to 2.21) for hemorrhagic type. The number of PNTR negatively correlated with Lp(a) levels. Low-number repeats (sum of both alleles <16) of apo(a) PNTR were associated with both atherothrombotic stroke (odds ratio, 1.41; 95% CI, 1.04 to 1.91) and hemorrhagic stroke (odds ratio, 1.62; 95% CI, 1.09 to 2.37). CONCLUSIONS: Our results indicate for the first time that low numbers of apo(a) PNTR and plasma Lp(a) levels are independently associated with both ischemic and hemorrhagic stroke in Chinese.

5' Untranslated Regions↗

PubMed2002

Endothelial dysfunction in cold-induced hypertensive rats.

Endothelial dysfunction can be observed in preatherosclerotic conditions. However, its pathogenetic role in hypertension is still controversial. Endothelial-dependent changes of blood pressure (BP) and expression of endothelial nitric oxide synthase (eNOS) were evaluated in cold-induced hypertensive rats. Wistar rats were exposed to cold stress for 8 weeks. Exposure to cold stress significantly increased the systolic BP in rats. The infusion of acetylcholine significantly lowered mean arterial BP in control rats by 48 +/- 2% and by 32 +/- 1% in cold-induced hypertensive rats. The acetylcholine-induced reduction of mean arterial BP was significantly attenuated in cold-induced hypertensive rats (control rats, 45 +/- 2 mm Hg; cold-induced hypertensive rats, 34 +/- 3 mm Hg; P < .05). Administration of N(G)-nitro-L-arginine-methyl ester for 1 week significantly increased BP in control rats, whereas no effect could be observed in cold-induced hypertensive rats. In cold-induced hypertensive rats eNOS in aortic vessels was significantly reduced compared to control rats. In this nongenetic, nonsurgical animal model of cold-induced hypertensive rats an endothelial dysfunction can be observed due to reduced eNOS.

Acetylcholine↗

PubMed2002

Angiotensin-(1-7) inhibits angiotensin II-induced signal transduction.

The inhibitory effects of angiotensin-(1-7) on angiotensin II-induced vasoconstriction, growth of vascular smooth muscle cells, stimulation of protein kinase C, extracellular signal-regulated kinases (ERK), and angiotensin subtype 1 receptor (AT1) and subtype 2 receptor (AT2) mRNA expression were investigated. The hemodynamic effects of angiotensin-(1-7) were measured in Wistar rats. Vasoconstriction was measured using aortic rings. DNA synthesis or protein synthesis was measured in cultured vascular smooth muscle cells using [3H] thymidine or [3H] leucine incorporation, respectively. Angiotensin II stimulated protein kinase C and ERK1/2 were measured by Western blot analysis using phosphospecific protein kinase C and ERK1/2 antibodies. AT1 and AT2 receptor mRNA expression was measured using reverse-transcription polymerase chain reaction. Infusion of angiotensin II significantly increased whereas infusion of angiotensin-(1-7) had no effects on mean arterial blood pressure in Wistar rats. Angiotensin-(1-7) dose-dependently showed partial antagonism on angiotensin II-induced contraction of aortic rings. Angiotensin-(1-7) showed partial antagonism on angiotensin II-induced DNA synthesis and protein synthesis. Angiotensin-(1-7) showed partial antagonism on angiotensin II-induced activation of protein kinase C and ERK1/2. The administration of angiotensin-(1-7) showed partial antagonism on angiotensin II-induced downregulation of AT1 receptor mRNA expression, whereas AT2 receptor mRNA expression was unchanged. Angiotensin-(1-7) showed partial antagonism on angiotensin II-induced intracellular signal transduction and may play a crucial role in the adaptation process of AT1 receptors to sustained stimulation of angiotensin II.

Angiotensin I↗

PubMed2002

[The plasma levels of proinsulin and true insulin and the effects of ramipril in hypertension].

OBJECTIVE: To explore the dynamic changes of plasma proinsulin (PI) and true insulin (TI) and their relation with essential hypertension (EH) as well as to evaluate the therapeutic effect of ramipril. METHODS: PI, TI and immunoreactive insulin (IRI) were measured in 44 cases of EH, 24 normal subjects and 21 cases of EH before and after treatment with ramipril. RESULTS: The mean plasma level of PI and IRI in EH was significantly higher than that in the control group (P < 0.01); there was no significant difference in the level of TI (P > 0.05). PI was positively related to TI, There was no significant relation between PI with SBP and DBP. Plasma concentration of IRI and PI (P < 0.05), decreased remarkably, but the level of TI remained unchanged after therapy with ramipril (n = 21). CONCLUSION: The plasma concentration of PI is elevated in patients with EH due probably to impaired function of beta-cells of the pancreatic islets. Ramipril can decrease the level of PI and improve pancreatic beta cell function.

Adult↗