[Primary cardiac angiosarcoma in the left atrium with adrenal metastasis; report of a case].

We encountered a 61-year-old woman with primary cardiac angiosarcoma in the left atrium. On echocardiography, the tumor extended into the atrial septum and mitral valve, and mitral valve stenosis and regurgitation were significant. We resected the tumor protruding into left atrium, and affecting mitral valve. The surgical procedure was not radical, but on postoperative echocardiography, function of the mitral valve was improved. Three months later, elevation of her right diaphragma was observed on chest X-ray and a giant adrenal tumor was detected by magnetic resonance imaging. Tumor biopsy indicated that this tumor was adrenal metastasis from cardiac angiosarcoma. In addition, echocardiography showed the recurrence of angiosarcoma in the left atrium and the presence of mitral stenosis and regurgitation. She died of heart failure 185 days postoperatively.

Apoptosis and glomerular injury after prolonged nitric oxide synthase inhibition in spontaneously hypertensive rats.

This study was designed to investigate the relationship between apoptosis and glomerular injury in spontaneously hypertensive rats (SHR) with hypertensive disease that was exacerbated by inhibition of NO synthesis. Development of glomerular cell apoptosis was evaluated by assessment of renal hemodynamics, glomerular morphometric changes, and participation of the renin-angiotensin system. Three groups of 20-week-old SHR were investigated: control male SHR and 2 similar groups given 2 doses of N(G)-nitro-L-arginine methyl ester (L-NAME, 50 or 80 mg/L, respectively) for 3 weeks. Mean arterial pressure and renal vascular resistance increased, whereas effective renal plasma flow and glomerular filtration rate were diminished by L-NAME. The small artery wall/lumen ratio increased as the glomerular-tuft area diminished. Renal cortical tissue levels of angiotensin II increased in response to the L-NAME, thereby inducing afferent arteriolar injury. Apoptosis and proliferative index (PCNA) of nonsclerotic glomeruli were induced by the low-dose L-NAME as the glomerular cell number decreased. In contrast, the PCNA index was downregulated with the high-dose L-NAME. These results indicate that angiotensin II activation, induced by L-NAME, was related to glomerular cell deletion and apoptosis together with the pathophysiological changes of severe nephrosclerosis and impaired renal dynamics.

Hydroxyl radical generation and lipid peroxidation in C2C12 myotube treated with iodoacetate and cyanide.

To mimic exercise-induced events such as energetic impairment, free radical generation, and lipid peroxidation in vitro, mouse-derived C2C12 myotubes were submitted to the inhibition of glycolytic and/or oxidative metabolism with 1 mM iodoacetate (IAA) and/or 2 mM sodium cyanide (CN), respectively, under 5% CO2/95% air up to 180 min. Electron spin resonance (ESR) analysis with a spin-trap 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) revealed time-course increases in spin adducts from hydroxyl radical (DMPO-OH) and carbon-centered radical (DMPO-R) in the supernatant of C2C12 myotubes treated with the combination of IAA + CN. In this condition, malondialdehyde (MDA) and lactate dehydrogenase (LDH) were released into the supernatant. By the addition of iron-chelating 1 mM deferoxamine to the C2C12 preparation with IAA + CN, both ESR signals of DMPO-OH and DMPO-R were completely abolished, and the release of MDA and LDH were significantly reduced, while cyanide-resistant manganese superoxide dismutase had negligible effects on these parameters. Hence, a part of the injury of C2C12 myotube under IAA + CN was considered to result from the lipid peroxidation, which was induced by hydroxyl radical generated from iron-catalyzed systems such as the Fenton-type reaction. This in vitro model would be a helpful tool for investigating the free radical-related muscle injury.

Lipid peroxidation, antioxidative enzyme activities, and cytosolic free calcium levels in rat hippocampus-derived cells exposed to free radicals.

To elucidate mechanisms of free radical-induced neuronal cell death, lipid peroxidation measured as thiobarbituric acid-reactive substances (TBARS), three antioxidative enzyme activities (superoxide dismutase, glutathione peroxidase, and catalse), and cytosolic free Ca2+ (Ca2+i) were examined in rat hippocampus-derived cells (HV16-4) exposed to free radicals generated by a hypoxanthine-xanthine oxidase system. The viability of cells decreased with an increase in numbers of free radical positive cells in a dose-dependent manner of xanthine oxidase. The protein-bound TBARS did not change, whereas free TBARS increased at 135% of initial value. No remarkable change was observed in three antioxidative enzyme activities. On the other hand, Ca2+i increased after exposure followed by cell death. Furthermore, the addition of Co2+, a nonspecific Ca2+ channel blocker, delayed the increase of Ca2+i and subsequent cell death. These findings suggested that the influx of Ca2+ played a crucial role for HV16-4 cell death induced by free radicals.

Effect of trichlormethiazide and captopril on nitric oxide synthase activity in the kidney of deoxycorticosterone acetate-salt hypertensive rats.

Nitric oxide (NO) production is reduced in patients with essential hypertension and in some experimental models. We have investigated the effect of trichlormethiazide and captopril on NO synthase (NOS) activity and glomerular damage in the kidney of deoxycorticosterone acetate (DOCA)-salt hypertensive rats. DOCA-salt rats were induced with weekly injections of DOCA (30 mg/kg body weight (BW) and 1% saline in drinking water after right nephrectomy. As antihypertensive therapies, CAP (captopril, 40 mg/kg BW) and TCM (trichlormethiazide, 10 mg/kg BW) were given after induction of DOCA-salt hypertension. The increased blood pressure was significantly lowered by TCM, but not by CAP after 5 weeks. Nitrite production in kidney slices was suppressed in DOCA-salt rats, and immunoreactivity for both brain-type NOS (B-NOS) in macula densa and endothelial-type NOS (EC-NOS) in renal vessels was decreased. TCM significantly increased the nitrite production in the kidney slices and B-NOS immunoreactivity, whereas these changes were less in CAP. Glomerulosclerosis score was significantly higher in DOCA-salt rats, and TCM ameliorated renal damage more effectively than CAP. These results indicate that the reduced nitrite production in the kidney of DOCA-salt hypertensive rats was increased more effectively by trichlormethiazide than by captopril, via increased immunoreactivity for B-NOS in the macula densa, and prevented renal damage.

[Effects of nisoldipine in heminephrectomized spontaneously hypertensive rats--measurement of afferent and efferent arterioles by microvascular cast].

In this study, we measured cross sectional areas of glomerular arterioles and glomerular volume in heminephrectomized spontaneously hypertensive rats (SHR) treated with a calcium antagonist, nisoldipine (NSL). We also examined the relevance of these parameters to the progression of hypertensive renal injury. Male 6-week-old SHR (n = 14) were heminephrectomized and divided into 2 groups. They were fed regular chow (control, n = 7) or chow containing 0.1% NSL (n = 7). After 12 weeks, urinary protein excretion (UpV) and systolic blood pressure (SBP) were measured. The control rats developed marked hypertension reaching 228 +/- 2 mmHg, and NSL lowered this by 27 mmHg (p < 0.001). NSL reduced UpV by 22% (p < 0.05). Microvascular cast of the kidney was prepared, and the cross sectional areas of the afferent and efferent arterioles as well as glomerular volume were measured using scanning electron microscopy. In the juxtamedullary and subcapsular glomeruli with minor abnormalities, the afferent arteriole was narrower and the glomerular volume was smaller in the NSL-treated rats than in the control rats. These results suggest that the calcium antagonist, NSL, offers the advantage of protecting kidney from hypertensive injury by reducing afferent arteriolar diameter, glomerular hypertrophy and intraglomerular pressure in heminephrectomized SHR.