Adult ; Arsenic Poisoning ; pathology ; Chronic Disease ; Hemosiderin ; metabolism ; Hemosiderosis ; metabolism ; pathology ; Humans ; Hypertension, Portal ; chemically induced ; metabolism ; pathology ; Liver Cirrhosis ; chemically induced ; metabolism ; pathology ; Male ; Pancytopenia ; chemically induced ; metabolism ; pathology ; Splenomegaly ; chemically induced ; metabolism ; pathology

Animals ; Hypertension, Pulmonary ; chemically induced ; physiopathology ; Monocrotaline ; adverse effects ; Rats ; Rats, Sprague-Dawley ; Thrombomodulin ; metabolism

OBJECTIVETo observe the changes in pulmonary artery protein kinase C (PKC) activity in rats with chronic inflammatory pulmonary hypertension (PHT).

METHODSChronic inflammatory PHT was induced in rats with monocrotaline. The PKC activities in the rat pulmonary arteries were measured by radioactive assay during the development of PHT.

RESULTSWith the development of chronic inflammatory PHT, the total and cytosolic fractions of PKC activity in PHT rat pulmonary arteries increased initially with subsequent decrease (Plt;0.05), but the membranous fraction of PKC activity and the membrane-to-cytosol PKC activity ratio increased continuously (P<0.05).

CONCLUSIONThe up-regulation of PKC activity and the translocation of PKC might be associated with the development of chronic inflammatory PHT in rats.

Animals ; Chronic Disease ; Hypertension, Pulmonary ; chemically induced ; enzymology ; Inflammation ; chemically induced ; enzymology ; Male ; Monocrotaline ; Protein Kinase C ; metabolism ; Pulmonary Artery ; enzymology ; Rats ; Rats, Wistar

OBJECTIVETo explore the mechanism of pulmonary hypertension and Cor Pulmonale rat models induced by monocrotaline (MCT).

METHODSTwenty Wistar male rats were randomly divided into normal control group and model group (n= 10), which received a single intraperitoneal injection of MCT solution (50 mg/kg , the first day) or dissolvant, respectively. On day 28 after MCT administration, the hemodynamic parameters were assessed; levels of tumour necrosis factor-alpha (TNF-alpha), nitric oxide (NO), endothelin-1 (ET-1), B-type natriuretic peptide(BNP) in pulmonary tissue or blood were measured using radio immunoassay or nitrate reductase method.

RESULTS28 days after MCT injection, compared with control group, right ventricle systolic pressure (RVSP) increased and heart rate(HR), mean arterial pressure (MAP) decreased; Levels of TNF-alpha, NO, ET-1 in pulmonary tissue or blood increased significantly in MCT group.

CONCLUSIONThe potential mechanism of MCI- induced pulmonary hypertension and Cor Pulmonale rat models associates with increasing TNF-alpha, NO, ET-1 levels in vivo, which results from inflammatory injury of lung tissue and blood vessels induced by MCT.

Animals ; Disease Models, Animal ; Endothelin-1 ; metabolism ; Hypertension, Pulmonary ; chemically induced ; metabolism ; physiopathology ; Lung ; metabolism ; Male ; Monocrotaline ; adverse effects ; Nitric Oxide ; metabolism ; Pulmonary Heart Disease ; chemically induced ; metabolism ; physiopathology ; Rats ; Rats, Wistar ; Tumor Necrosis Factor-alpha ; metabolism

To explore the changes in adrenomedullin (ADM) and receptor activity-modifying protein 2 (RAMP2) mRNA in myocardium and vessels in hypertension, a hypertensive rat model was prepared by administering L-NNA. Contents of ADM in plasma, myocardium and vessels were measured by radioimmunoassay (RIA). The levels of pro-ADM mRNA of myocardium and vessels were determined by competitive quantitative RT-PCR. The results showed that L-NNA induced hypertension and cardiomegaly. The ratio of heart to body weight increased by 35.5% (P<0.01). In hypertensive rats the ir-ADM in plasma, myocardium and vessels was increased by 80%, 72% and 57% (P<0.01), respectively compared with the control. The amounts of ADM mRNA in myocardium and vessels were increased by 50% and 109.2% (P<0.05), respectively, and the amounts of RAMP2 mRNA was increased by 132% and 87% (P<0.01), respectively, compared with control. The levels of ADM in myocardium and vessels were positively correlated with RAMP2 mRNA, the correlation coefficients were 0.741 and 0.885 (P<0.01), respectively. The results obtained indicate that in hypertensive rats, ADM is elevated in plasma, myocardium and ves-myocardium and vessel, and ADM and RAMP2 mRNA are up-regulated in myocardium and vessel. The ADM/RAMP2 system may play an important role in the pathogenesis of hypertension.
Adrenomedullin ; metabolism ; Animals ; Cardiomegaly ; chemically induced ; metabolism ; Hypertension ; chemically induced ; metabolism ; Myocardium ; metabolism ; Nitroarginine ; pharmacology ; RNA, Messenger ; Rats ; Receptor Activity-Modifying Protein 2 ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Up-Regulation

OBJECTIVETo investigate renal sodium handling of ouabain-hypertensive rats and the role of renal sodium handling in pathogenesis of hypertension using endogenous trace lithium as a marker of proximal sodium reabsorption.

METHODSForty male Sprague-Dawley (SD) rats weighting 180-220 g were equally divided into normal control group and ouabain group randomly. Rats were infused with normal saline 1 ml/ (kg x d) or ouabain 27.8 microg/ (kg-d) intraperitoneally once a day respectively. Systolic blood pressure (SBP) and body weight were recorded weekly. Rats were sacrificed after 2 and 6 weeks respectively. Blood and 24 hour urine sample were collected to measure the serum and urinary concentration of sodium, potassium, trace lithium, and creatinine. Endogenous creatinine clearance rate (Ccr), fractional excretions of sodium (FE(Na)), and fractional excretions of lithium (FE(Li)), the ratios of urinary lithium to sodium (U(Li)/U(Na)), the ratios of urinary potassium to sodium (U(K)/U(Na)), and fractional reabsorption of sodium in the postproximal tubules (FDR(Na)) were also calculated. All were studied on their normal diet and ate salt freely.

RESULTSBlood pressure had no significant difference in these two groups after 2 weeks (P > 0.05); After 4 weeks, however, blood pressure was significantly higher in ouabain group than in control group (P < 0.01). Body weight of rats had no significant difference during the experiment period (P > 0.05). Ccr and FE(Na) were similar in these 2 groups (P > 0.05). FE(Li), U(Li)/U(Na), U(K)/U(Na), and FDR(Na) of ouabain group were significantly lower than control group after 2 and 6 weeks (P < 0.05, P < 0.01, P < 0.001 respectively).

CONCLUSIONThe reabsorption of sodium increases in the proximal tubule in ouabain-hypertensive rats, and such increase occurs before the development of hypertension. Therefore, increase of proximal reabsorption of sodium may be involved in the pathogenesis of ouabain-induced hypertension.

Animals ; Hypertension ; chemically induced ; metabolism ; Kidney Tubules, Proximal ; metabolism ; Lithium ; metabolism ; Male ; Natriuresis ; Ouabain ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Sodium ; metabolism

OBJECTIVETo investigate the changes in renal sodium transport during development of hypertension in ouabain-hypertensive rats (OHR) and further elucidate the role of ouabain in the pathogenesis of hypertension.

METHODSEighty male SD rats weighing 80-100 g were randomized equally into normal control and ouabain groups and treated with intraperitoneal injection of normal saline (1 ml/kg) and ouabain (27.8 microg/kg) once daily, respectively. Systolic blood pressure (SBP) and body weight of the rats were recorded weekly. One week before sacrifice scheduled at weeks 2, 4, 6 and 8, respectively, the rats were individually housed in metabolic cages to determine food consumption twice. Blood and 24-hour urine samples were collected to measure serum and urine concentration of sodium, trace lithium and creatinine. Endogenous creatinine clearance rate (Ccr), fractional excretions of sodium (FENa), fractional excretions of lithium (FELi) and fractional reabsorption of sodium in the distal tubules (FDRNa) were calculated.

RESULTSThe body weight and food intake between ouabain groups and control groups were comparable during the experiment (P>0.05). Blood pressure was also comparable in the two groups after 2 weeks (P>0.05). At week 4, however, blood pressure of ouabain group was significantly higher than that of the control group (P<0.001) and increased in a dose-dependent manner. The SBP in ouabain group appeared to reach a plateau at week 7. Ccr and plasma sodium (PNa) were similar in the 2 groups during the experiment (P>0.05). FELi was significantly lower at weeks 2, 4 and 6 in ouabain group than in the control group (P<0.01), and FELi decrement in ouabain group was accompanied by reduced sodium excretion. FENa was significantly lower at week 4 in ouabain group than in the control group (P<0.05), but this difference was not significant in weeks 2 and 6 (P>0.05). At weeks 2, 4 and 6, ouabain group showed significantly lower FDRNa than the control group (P<0.05), suggesting the compensation of the distal nephron segments. After 8 weeks, FENa, FELi and FDRNa were similar between the two groups (P>0.05).

CONCLUSIONSOuabain can increase renal proximal tubule reabsorption of sodium and consequently decrease renal sodium excretion in OHR, which can contribute to alteration of the pressure-natriuresis relationship in OHR, and play an important role in the development and maintenance of hypertension of OHR.

Animals ; Blood Pressure ; Creatinine ; blood ; Hypertension ; chemically induced ; metabolism ; physiopathology ; Ion Transport ; Kidney Tubules, Proximal ; metabolism ; Male ; Ouabain ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Sodium ; blood ; metabolism

OBJECTIVETo investigate the role of renal sympathetic nerves in renal sodium transport in ouabain-hypertensive rats (OHR).

METHODSSixteen male SD rats with sham renal denervation (Sham-RDNX) and 16 with renal denervation (RDNX) were randomly into normal control group and ouabain group to receive intraperitoneal injection of normal saline (1 ml/kg) and ouabain (27.8 µg/kg) once a day, respectively. Systolic blood pressure (SBP), heart rate and body weight were recorded weekly. Food consumption of the rats was determined twice a week. After a 4-week treatment, blood and 24 h urine samples were collected to measure the serum and urinary concentration of sodium, trace lithium and creatinine. Endogenous creatinine clearance rate (Ccr), fractional excretions of sodium (FENa), fractional excretions of lithium (FELi) and fractional reabsorption of sodium in the postproximal tubules (FDRNa) were calculated. Plasma renin activity was determined by radioimmunoassay. Norepinephrine was extracted from the renal tissue and assayed for norepinephrine content by HPLC.

RESULTSThe body weight, food intake and heart rate showed no significant difference among the 4 groups (P > 0.05). After 4 weeks, the SBP of control RDNX group (CDNX) was significantly lower than that of the control Sham-DNX group (Csham)(P < 0.05); the SBP of ouabain RDNX group (ODNX) was also significantly lower than that of ouabain Sham-DNX group (Osham) (P < 0.05); RNDX lowered SBP by about 10 mmHg in both ouabain groups and control groups. The SBP was significantly higher in Osham and ODNX groups than in the corresponding control groups (P < 0.01), also significantly higher in ODNX group than in Csham group (P < 0.01). Ccr showed no significant difference among the 4 groups(P > 0.05). FENa, FELi and FDRNa were significantly lower in ouabain groups than in the corresponding control groups (P < 0.05, P < 0.01, P < 0.05), but FENa, FELi and FDRNa of ODNX group were similar with those of Osham group (P > 0.05); FENa , FELi and FDRNa were similar between CDNX and Csham groups (P > 0.05). The plasma renin activity was comparable between the 4 groups (P > 0.05). Renal norepinephrine level was markedly reduced in RDNX group compared with that in Sham-RDNX group in both ouabain and control groups (P < 0.01).

CONCLUSIONThe increase of proximal tubule sodium reabsorption in OHR is not dependent on the renal sympathetic nerve.

Animals ; Hypertension ; chemically induced ; metabolism ; Kidney ; innervation ; Male ; Ouabain ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Sodium ; metabolism ; Sodium Channels ; metabolism ; Sympathetic Nervous System ; physiology

The purpose of the present study was to explore the role of endogenous hydrogen sulfide (H2S) in pulmonary arterial hypertension induced by endotoxin. Adult male Sprague-Dawley (SD) rats were randomly divided into four groups: Control group (0.5 mL/kg body weight of normal saline, i.v.), lipopolysaccharide (LPS)-treated group (5 mg/kg body weight of LPS, i.v.), LPS + NaHS (5 mg/kg body weight of LPS, i.v., and 28 μmol/kg body weight of NaHS, i.p.) and LPS + PPG group (5 mg/kg body weight of LPS, i.v., and 30 μmol/kg body weight of PPG, i.p.). Rats were anesthetized with 20% urethane (1 g/kg body weight, i.p.). A polyethylene catheter was inserted into the pulmonary artery through the right external jugular vein to measure the mean pulmonary arterial pressure (mPAP) for 7 h, and then the pulmonary artery was isolated rapidly by the method described previously. Pulmonary arterial activity was detected. H2S concentration and cystathionine γ-lyase (CSE) activity in pulmonary artery tissues were determined by biochemical method. CSE mRNA expression was detected by competitive reverse transcriptase-polymerase chain reaction (RT-PCR). Compared with control, LPS significantly increased mPAP [(1.82±0.29) kPa vs (1.43±0.26) kPa, P<0.01], decreased H2S production [(26.33±7.84) vs (42.92±8.73) pmol/g wet tissue per minute, P<0.01), and reduced endothelium-dependent relaxation response [(75.72±7.22)% vs (86.40±4.40) %, P<0.01) induced by ACh (1×10(-6) mol/L). These effects were partly reversed by co-administration of NaHS and enhanced by co-administration of PPG. Both CSE activity and CSE mRNA expression were consistent with H2S production. It is suggested that the inhibitory effect of LPS on endothelium-dependent relaxation results in pulmonary hypertension, which might be mediated through H(2)S.
Animals ; Arterial Pressure ; Cystathionine gamma-Lyase ; metabolism ; Hydrogen Sulfide ; metabolism ; Hypertension, Pulmonary ; chemically induced ; metabolism ; Lipopolysaccharides ; adverse effects ; Male ; Rats ; Rats, Sprague-Dawley ; Sulfides ; pharmacology

OBJECTIVETo evaluate the contribution of platelet and leukocyte activation in pathogenesis primary pulmonary hypertension (PPH).

METHODSPulmonary hypertension was induced by subcutaneous injection of 2% monocrotaline (MCT) in male Prague-Dawley (SD) rats. Blood samples were collected at the third week after MCT injection, and flow cytometry was used to determine the fibrinogen-binding platelet, CD11b expression on leukocyte and platelet-leukocyte aggregation.

RESULTThree weeks after MCT injection, rats exhibited higher right ventricular systolic pressure (RVSP) and mean pulmonary artery pressure(mPAP), as compared with controls. MCT induced vascular remodeling characterized by vascular medial wall thickening in pulmonary muscular arteries. The ratio of platelets fibrinogen binding was increased in rats 3 weeks after MCT injection than that of control group[(4.08 +/-1.59)% compared with (1.45 +/- 0.61)%, P<0.01]. CD11b expression in monocytes and neutrophils, but not in lymphocytes was increased significantly 3 weeks after MCT injection (P <0.01). Platelet-neutrophil aggregations increased in MCT injected rats as compared with controls (P <0.01).

CONCLUSIONRats of PPH model demonstrate enhanced circulating platelet and leukocyte activation, which may contribute to the pathogenesis of PPH.

Animals ; Blood Platelets ; metabolism ; Fibrinogen ; metabolism ; Hypertension, Pulmonary ; blood ; chemically induced ; Leukocytes ; physiology ; Male ; Monocrotaline ; Platelet Aggregation ; Platelet Count ; Random Allocation ; Rats ; Rats, Sprague-Dawley