ABSTRACT
Alterations of autocrine function of pulmonary arterial smooth muscle cells (PASMCs) might play an important role in development of hypoxic pulmonary hypertension (HPH). To test this hypothesis, the effects of hypoxia on angiotensin II (AT II) secretion by cultured new born bovine PASMCs were investigated. AT II secretion decreased significantly when PASMCs were incubated under 2.5% O2 hypoxic condition for 3 to 48 h (P < 0.01 vs control), but decreased further under anoxic condition (P < 0.01 vs control and 2.5% O2 group). Nitric oxide (NO) donor SIN-1 inhibited AT II secretion significantly under normoxic condition, but NO synthase inhibitor L-nitro-arginine (LNA) eliminated the inhibitory effect of anoxia on AT II autocrine and promoted AT II release. It was also found that the concentration of cGMP in PASMCs increased significantly (P < 0.01) at 24 h incubation in 0% O2, an effect that can be attenuated by LNA. Hypoxia stimulated 3H-TdR incorporation of PASMCs significantly (P < 0.001), while captopril exerts an inhibition in normoxic condition (P < 0.001), but without effect under hypoxic condition. The above results suggest that hypoxia can inhibit AT II secretion by inducing endogenous NO production in PASMCs. AT II autocrine is not involved in hypoxic proliferation of PASMCs, but a decrease of AT II may contribute to prevention of the development of HPH.
Subject(s)
Angiotensin II/metabolism , Muscle, Smooth, Vascular/cytology , Nitric Oxide/metabolism , Animals , Animals, Newborn , Cattle , Cell Hypoxia , Cells, Cultured , Nitric Oxide Donors/pharmacology , Pulmonary Artery/cytologyABSTRACT
The effects of hypoxia on the bovine pulmonary arterial smooth muscle cell (PASM) proliferation and serotonin transporter gene expression were investigated using 3H-Thymidine incorporation, immunocytochemical staining and mRNA dot blot hybridyzation, the results were as follows, PASM 3H-Thymidine incorporation increased in response to anoxia for 24 h (P < 0.05). The anoxia-induced increased in DNA synthesis of PASM was significantly stimulated by 5-HT (100, 10 and 1 mumol/L) (P < 0.001), but 5-HT did not increase 3H-TdR incorporation under normoxic condition. Immunocytochemical reaction of serotonin in PASM under normoxic condition was markedly stronger than that of anoxic PASM (P < 0.001). Dot blot analysis showed hypoxia increased serotonin transporter mRNA expression of PASM (P < 0.01). These results indicate that stimulation of PASM proliferation with enhanced serotonin transporter gene expression and high consumption of 5-HT in hypoxia or/and anoxia may take part in the development of hypoxic pulmonany hypertention.
Subject(s)
Muscle, Smooth, Vascular/cytology , Serotonin/pharmacology , Animals , Animals, Newborn , Cattle , Cell Division/drug effects , Cell Hypoxia , Cells, Cultured , Hypertension, Pulmonary/metabolism , Pulmonary Artery/cytologyABSTRACT
AIM: To investigate the relationship between lactate dehydrogenase (LDH) activity or LDH isoenzyme patterns and the pathogenesis of colorectal cancer. METHODS: Activities of tissue LDH and LDH isoenzyme patterns in 16 patients with colorectal cancer were assayed using spectrophotometric procedures and agarose gel electrophoresis, respectively. RESULTS: The total and specific activities of LDH were significantly higher in colorectal cancer tissues than those in adjacent noncancerous tissues (P < 0.001). The LDH isoenzyme pattern was also different from that in the control. The percentage of LDH5 doubled and the ratio of LDH4 + LDH5/LDH1 + LDH2 was 3.6 ± 1.4 in cancer tissue, significantly greater than in the control. CONCLUSIONS: The increased LDH activity in colorectal cancer tissues resulted mainly from the increased LDH5, suggesting that the alteration of LDH activity and isoenzyme patterns were related to the pathogenesis of colorectal cancer.
ABSTRACT
Plasma levels of renin activity, angiotensin II and aldosterone were determined in 16 patients with high altitude pulmonary edema (HAPE) with radioimmunoassay and compared with those in the controls including 9 patients with high altitude acute response (HAAR) and 14 health subjects. All of them arrived recently in Lhasa, a place with an altitude of 3,658 m. The results showed that the concentration of plasma renin activity, angiotensin II, and aldosterone was significantly increased (P < 0.05-0.001) in patients with HAPE and higher than that in the controls. It is suggested that the increase plays a role in the development of pulmonary edema in patients with HAPE.
Subject(s)
Altitude Sickness/metabolism , Pulmonary Edema/metabolism , Renin-Angiotensin System , Adolescent , Adult , Aged , Angiotensin II/blood , Humans , Male , Middle Aged , RadioimmunoassayABSTRACT
Calcium channel blockers have emerged as important adjuncts to pharmacotherapy of hypertrophic cardiomyopathy. Nicardipine, a new hydropyridine calcium channel blocker, was evaluated for its short-term effects (14 days, 20 mg tid) on left ventricular function in 16 patients with hypertrophic cardiomyopathy (HCM) with UCG. Results indicated that heart rate, blood pressure and systolic function changed very little after nicardipine (P greater than 0.05). However, the following changes were noted after administration: IVRT decreased (132.4 +/- 21.2----120.7 +/- 27.0, P less than 0.02); left ventricular posterior wall rapid filling amplitude and mean velocity increased (8.86 +/- 2.23----9.68 +/- 2.41, P less than 0.01; 54.96 +/- 13.6----59.66 +/- 18.36, P less than 0.05); EF slope increased (3.52 +/- 1.33----3.88 +/- 1.37, P less than 0.01); left ventricular end diastolic pressure and pulmonary capillary wedge pressure decreased (11.79 +/- 3.32----9.72 +/- 2.46, P less than 0.01; 11.11 +/- 2.97----9.19 +/- 2.42, P less than 0.01). The conclusion is that nicardipine may improve left ventricular diastolic function of patients with HCM without serious side effects. It is valuable to conduct further study.
Subject(s)
Cardiomyopathy, Hypertrophic/drug therapy , Heart/physiopathology , Nicardipine/therapeutic use , Cardiomyopathy, Hypertrophic/physiopathology , Double-Blind Method , Echocardiography , Heart Ventricles/physiopathology , Humans , Random AllocationABSTRACT
The long-term sequelae of vasectomy were studied in a retrospective cohort study of 4596 vasectomized and 4340 nonvasectomized farmers from eight rural communes in Sichuan, People's Republic of China. The mean duration since the operation was 14.5 years with a range of 10 to 25 years. At the time of evaluation the vasectomized men were generally healthier than the non-vasectomized for a wide range of health indicators including clinical signs of cardiovascular disease, resting ECG changes, positive ECG changes following a maximal stress test, or fundus abnormalities. The lack of association between vasectomy and cardiovascular disease noted in Europe and the USA is supported by the present study conducted in a population with a low prevalence of cardiovascular disease and risk factors.
PIP: A study was conducted in Sichuan, China to further determine if any correlation exists between vasectomy and the risk of heart disease. In a retrospective analysis of 4596 men who had received vasectomies and 4340 who had not been vasectomized, it was found that the cardiovascular status of men who had had a vasectomy was actually better that those who had not. The mean duration since the operation was 14.5 years with a range of 10-25 years. The results confirmed past conclusions that vasectomy is not linked with coronary disease. Testing for other endpoints and areas such as stomach ulcer and hypertension indicated that men who had received a vasectomy were in general in better health. Resting ECG changes and positive ECG changes following a stress test further confirmed the results. Mortality associated with vasectomy was also examined with no negative connection found. Vasectomy has been extensively studied and has been proven repeatedly to be a safe procedure that is not linked to adverse effects.