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To observe the dynamic changes of plasma adrenomedullin (ADM) levels and the effect of enalapril intervention in diabetic rats.Fifty-two wistar rats were grouped into 1- and 3-month groups (7 each), both including a control and a streptozotocin-induced diabetic group. The 5-month group was divided into control, diabetic and enalapril-treatment diabetic groups (8 each, the last group receiving oral enalapril treatment at the daily dose of 2 mg/kg from the first to the fifth month after diabetes induction). Blood samples were collected from the heart of the rats at the end of 1, 3 and 5 months for determination of plasma ADM concentrations radioimmunoassay.Plasma ADM levels were significantly higher in diabetic rats than in the corresponding control rats in 1- and 3-month groups. ADM levels in the diabetic rats of 5-month group were significantly decreased in comparison with that of 1- and 3-month groups. In 5-month group, plasma ADM levels of enalapril-treated diabetic rats elevated significantly in comparison with that in the control rats and the diabetic rats without enalapril treatment.ADM may play an important role in the pathophysiology of diabetes.

To investigate the changes of plasma hydrogen sulfide (H(2)S) in patients with coronary heart disease (CHD).Plasma H(2)S levels were measured in 40 patients with CHD and 17 angiographically normal patients by sulfide-sensitive electrodes, and the variation of plasma H(2)S levels was analyzed in different clinical types of CHD and in different types of coronary artery lesions. The association of plasma H(2)S levels with the risk factors of CHD was also analyzed.Plasma H(2)S levels were significantly lowered in CHD patients in comparison with that in angiographically normal control subjects (26.10+/-14.27 micromol/L vs 51.74+/-11.94 micromol/L, P0.001). In CHD patients, plasma H(2)S levels in unstable angina patients (UAP, 23.60+/-14.41 micromol/L) and acute myocardial infarction patients (AMI, 19.98+/-7.516 micromol/L) were significantly lower than that in stable angina patients (SAP, 38.41+/-14.53 micromol/L, P0.05). No significant difference in plasma H(2)S levels was found between CHD patients with double-vessel and multi-vessel lesions (16.91+/-7.98 vs 18.39+/-7.78 micromol/L, P0.05), but the two groups of patients had significantly lower plasma H(2)S levels than patients with single-vessel involvement (33.04+/-15.01 micromol/L, P0.05 and P0.01, respectively). Plasma H(2)S level was significantly lower in CHD patients with coronary artery occlusion than in patients with simple stenosis (19.04+/-9.55 vs 28.24+/-14.85 micromol/L, P0.05). Among the CHD patients, H(2)S levels were significantly lower in smokers than in non-smokers (27.54+/-10.37 vs 32.24+/-15.77 micromol/L, P0.05), also lower in hypertensive patients than in normotensive patients (20.36+/-8.69 vs 33.77+/-15.86 micromol/L, P0.01). Plasma H(2)S levels showed a significant inverse correlation with blood glucose (r=-0.493 6, P=0.001 6), but there were no significant correlations with sex, age, cholesterol, triglyeride, TC, low-density lipoprotein, high-density lipoprotein, or body mass index.Decreased plasma H(2)S levels may correlate with the severity of CHD and changes of the coronary artery, and may implicate the risk factors of CHD such as smoking, hypertension, and high blood glucose.

To study the mechanism of urotensin II(U II)-stimulated adrenomedullin secretion in human vascular endothelial cells.In cultured human vascular endothelial cells (HEVCs), different concentrations of U II was used to stimulate the secretion of Adm, and different inhibitors were used to study the changes in the secretion after block of different signal transduction pathways. The contents of Adm in the medium were detected with radioimmunoassay.U II-stimulated Adm secretion in the HEVCs in a time- and concentration-dependent manner. Adm contents of the treatment groups were comparable with that of the control group (P0.05 ), and the secretion of Adm could be inhibited by the inhibitor of extracellular signal-regulated protein kinases (PD098059), p38 kinase inhibitor (SB202190), calmodulin inhibitor (W7) and Ca(2+) inhibitor (nicardipine)(P0.05), but calcineurin inhibitor and protein kinase C inhibitor (H7) had no such effect (P0.05).Ca(2+), MAPK, CaM-PK and p38 signal transduction pathways may play major roles in U II-stimulated secretion of Adm in HVECs.

To evaluate the effect of percutaneous intervention (PCI) on coronary circulation levels of adrenomedullin (ADM) and tumor necrosis factor alpha (TNF-alpha) in patients with coronary heart disease (CHD).Thirty-three CHD patients underwent percutaneous transluminal coronary angioplasty (PTCA) and stenting (altogether 48 stents were implanted). Blood samples were collected from the coronary sinus and femoral artery at the time points of immediately before and after angioplasty, immediately after PTCA or stenting, 10 min after procedures, respectively.The ADM and TNF-alpha levels in the coronary sinus varied little after coronary angiography, but were elevated markedly following PTCA from the basal levels of 36.3+/-1.3 pg/ml to 28.9+/-1.9 pg/ml (P0.01) and from 11.10+/-0.46 ng/ml to 8.84+/-0.37 ng/ml (P0.01), respectively. Further increases of ADM and TNF-alpha levels were detected immediately after stent deployment. ADM recovered to basal levels 10 min after completion of the procedures, while TNF-alpha underwent further increase. Before the procedure, ADM and TNF-alpha levels were higher in the coronary sinus than in the femoral artery (28.9+/-1.9 pg/ml vs 22.6+/-0.8 pg/ml, P0.01; 8.84+/-0.37 ng/ml vs 7. 56+/-0.23 ng/ml, P0.01, respectively), and their levels in the femoral artery did not undergo significant changes in response to the operations.The coronary circulation levels of ADM and TNF-alpha increase after PTCA and stenting but not after coronary angiography in CHD patients, which might be attributed to injuries by the procedures as well as the mechanical stimulation by the stent.

To investigate the changes in plasma urotensin II(U II) expression levels in patients with coronary heart disease (CHD).Plasma U II levels in 50 CHD patients with coronary stenosis indicated by coronary angiography and 20 healthy subjects were determined by radio immunoassay.Venous plasma U II levels were significantly lowered in CHD patients in comparison with the healthy subjects (1.61+/-1.02 pg/ml vs 3.70+/-1.30 pg/ml, P=0.000). In the CHD patient group, significantly differences were noted in the U II levels between patients with stable angina (2.62+/-1.20 pg/ml), unstable angina (1.39+/-0.80 pg/ml) and acute myocardial infarction (AMI, 1.04+/-0.45 pg/ml, P=0.004). CHD patients with coronary artery occlusion and those with only coronary stenosis had comparable venous plasma U II levels (1.29+/-1.02 pg/ml vs 1.76+/-1.00 pg/ml, P=0.131), whereas the patients with restenosis after percutaneous transluminal coronary angioplasty (PTCA) had higher U II levels than the other subjects in the CHD patient group (2.28+/-0.94 pg/ml vs 1.40+/-0.96 pg/ml, P=0.008), and the femoral plasma U II levels were significantly elevated after PTCT, increasing from 1.18+/-1.14 pg/ml to a postoperative level of 2.22+/-1.77 pg/ml (P=0.001).U II might play a role in the pathophysiological process of CHD and can be involved in the restenosis after angioplasty.

To assess the expression intensity of urotensinII (UII) in normal and atheromatous human coronary artery and explore its significance in coronary atherosclerosis.Specimens of coronary arteries were obtained from 5 normal subjects and the expression of human UII in the specimens was detected by immunohistochemical method.UII expression was found in the endothelial cells (ECs), foam cells (FCs), inflammatory cells (ICs) and intima smooth muscle cells (ISMs) of human coronary artery. Even in the normal coronary artery, UII expression could be detected immunohistochemically in the ECs, which, however, was characterized by higher UII expression levels in fatty streak lesions but by almost normal levels in fibrous and atheromatous plaque in the coronary artery. Enhanced UII expression was observed in FCs and ICs when fibrous plaque and atheromatous plaque developed in comparison with that in fatty streak lesions. The ISMs in all the lesions had mild UII immunoreactivity, but as the atherosclerosis exacerbated, the immunoreactivity tended to intensify.Human UII may regulate the functions of ECs, FCs, ICs and ISMs in the development and progression of coronary atherosclerosis.

To investigate the changes of plasma urotensinII (UII) levels in patients with congestive heart failure (CHF) of different severities and their clinical implications.Plasma UII was determined by radioimmunoassay in 45 patients with CHF and 20 healthies control subjects. In all the subjects, the left ventricular fraction (LVEF) and the ratio of E/A were measured by echocardiography.The plasma UII level was significantly lowered in CHF patients in comparison with that in control subjects (1.41+/-1.09 pg/ml vs 4.35+/-1.22 pg/ml, P=0.000). A significant correlation of plasma UII level with LVEF (r=0.540, P=0.000) and the E/A ratio was observed (r=0.539, P=0.000), and the severity of CHF was shown to be inversely correlated with plasma UII levels in the patients (r=-0.656, P=0.000), which was elevated after treatment.UII might play a role in the pathophysiological process of CHF, and its plasma level may serve as an indicator of the severity of CHF.

To study the changes in plasma adrenomedullin (ADM) and proadrenomedullin N-terminal 20 peptide (PAMP) concentrations and their clinical significance in the pathological process of congestive heart failure (CHF).Plasma ADM and PAMP concentrations in 45 patients with CHF (according to the functional classification of New York Heart Association, NYHA) and 20 control subjects were measured by specific radioimmunoassay.Plasma ADM concentrations were 51.464+/-.52 pg/ml and 70.39+/-3.22 pg/ml respectively in patients of NYHA class II and class III, which were significantly higher than those in control subjects (24.12+/-1.59 pg/ml, P0.05 for both comparisons), while significant differences in plasma PAMP concentrations were not identified in the 2 groups of patients (6.24+/-1.71 pg/ml and 7.38+/-1.28 pg/ml, respectively) in comparison with the control level(8.56+/-2.44 pg/ml, P0.05 for both comparisons). Patients of NYHA class IV, when compared with the 2 groups of patients mentioned above, had significantly decreased plasma ADM and PAMP concentrations (36.33+/-2.17 pg/ml and 2.79+/-0.89 pg/ml respectively, P0.05 in both cases), but had higher plasma ADM and lower PAMP concentrations when compared with the control subjects, (P0.05 respectively).The changes of plasma ADM and PAMP concentrations at different stages of CHF indicate intramolecular regulation disturbances of vasodilator peptides of proadrenomedullin, and ADM may play a more important role in the development of CHF.

The author reviewed the structure of human urotensin-II and its receptor, also with regard to its distribution and biological effect on cardiovascular system.