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Background. Unlike acquired thrombotic thrombocytopenic purpura or haemolytic uraemic syndrome, which are often intractable, thrombotic microangiopathy in patients with Upshaw–Schulman syndrome (USS) – a congenital deficiency of von Willebrand factor-cleaving protease (ADAMTS13) activity – responds very well to plasma infusion and does not even require plasma exchange. However, the symptoms significantly vary in each individual and thus clinicians often overlook this diagnosis. Methods. A 31-year-old adult male patient with thrombotic microangiopathy, which was complicated with repeated episodes of acute renal failure, is reported. We suspected that the patient had USS and performed assays of ADAMT13 activity and its inhibitor, followed by ADAMTS13 gene analysis of the patient and his parents. Results. The patient had extremely low ADAMTS13 activity and has no inhibitors of ADAMTS13. Through an ADAMTS13 gene analysis of this family, we found two novel mutations responsible for the disease: a missense mutation in exon 7 [702 C ! A (H234Q)] from the father and a nonsense mutation in exon 26 [3616 C ! T (R1206X)] from the mother. Conclusions. Our experience appears to indicate the importance of assays of ADAMTS13 activity and its inhibitor in patients who have episodes of renal insufficiency in association with thrombotic microangiopathy, for diagnosis and choice of treatment.

The objective of the present study was to compare the effects of the vasodilating nonselective beta-adrenoceptor blocker nipradilol on renal microvasculature with those occurring with propranolol, a typical nonselective beta-adrenoceptor blocker. Hydronephrosis was induced by ligation of the left ureter in seventeen 8-week-old stroke-prone, spontaneously hypertensive rats. The experiment was performed 2 months after the surgery. The hydronephrotic kidney was split longitudinally and spread out as a thin sheet, and the renal microvasculature was observed directly under a light microscope. Intravenous administration of nipradilol 200 μg/kg as a bolus caused a significant decrease in the systolic blood pressure (−36 mm Hg) at 5 minutes. The afferent arteriole was significantly dilated transiently (+13% in diameter) at 10 minutes. The changes in the efferent arteriole were not statistically significant. The glomerular blood flow was statistically significantly increased (+22%) at 10 minutes. Intravenous administration of propranolol 600 μg/kg did not cause statistically significant changes in the systolic blood pressure, the afferent arteriolar diameter, or the glomerular blood flow. The efferent arteriole showed a statistically significant constriction (−16% in diameter) at 20 minutes. In summary, nipradilol dilated the afferent arteriole and increased the glomerular blood flow despite a significant decrease in the systolic blood pressure. This vasodilating effect on the afferent arteriole was not observed with propranolol.

Summary: The aim of this study was to determine the phenotypic modulation in preglomerular vascular smooth muscles and glomerular cells in hypertension. Eight-week-old stroke-prone spontaneously hypertensive rats (SHRSP) fed high sodium pellets (3%) were untreated or treated with a calcium antagonist, manidipine HCI (2 mg/kg per day), for 8 weeks. the expression of myosin heavy chain isoforms (MHC), SM2 (muscletype) and SMemb (non-muscle-type) or α-actin was examined by the immunohistochemical technique. In normotensive Wistar-Kyoto rats, both SM2 and α-actin were expressed equally in the smooth muscles of preglomerular vessels, and SMemb was expressed slightly in the glomerular epithelial cells. In the SHRSP, however, the expression of SM2 and α-actin was significantly decreased or disappeared in the afferent arterioles, depending on the degree of vascular damage. In damaged glomeruli, SMemb and α-actin were newly expressed in mesangial cells. Manidipine HCI attenuated the renal damage and restored the expression of α-actin in the afferent arterioles. There was a significant correlation between the glomerular damage and the attenuation of SM2 expression (r=0.87). In conclusion, phenotypic modulation of vascular smooth muscles occurred in hypertensive renal damage and was correlated with the glomerular damage, where the phenotypic modulation also took place in the mesangial cells. These results indicate that the phenotypic modulations revealed by the expression of myosin isoforms might play an important role in the development of hypertensive renal damage.

The objective of this study was to investigate the effects of amlodipine, a dihydropyridine calcium channel blocker, on renal microvasculature in hypertensive rats. Hydronephrosis was induced by permanent ligation of the left ureter in 8-week-old spontaneously hypertensive rats. After the hydronephrotic left kidney was split longitudinally and spread out as a thin sheet, the renal microvasculature was observed directly under a light microscope. Administration of amlodipine 200 μg/kg caused a gradual fall in systolic blood pressure (39 mm Hg). The afferent arterioles were dilated and maintained the same level of dilation after 60 minutes (19% at 5 minutes and 21% at 60 minutes at the diameter). The efferent arterioles were similarly dilated (14% at 5 minutes and 18% at 60 minutes). The glomerular blood flow was significantly increased (28% at 5 minutes and 46% at 60 minutes). We concluded that amlodipine dilated both the afferent and efferent arterioles and increased the glomerular blood flow.

Background/Aims: We previously showed that the mesangial expression of nonmuscle-type myosin heavy chain, SMemb, was related to glomerular sclerosis. Although angiotensin II (AII) is known to promote the glomerular accumulation of extracellular matrix and sclerosis, the effect of AII on the mesangial expression of SMemb is unknown. Thus, we investigated the effect of AII on the mesangial expression of SMemb and synthesis of fibronectin. Methods: We continuously administered AII to Sprague-Dawley rats with subcutaneous osmotic minipumps for 14 days. Control animals received normal saline instead. The effects of oral administration of an AII type 1 (AT1) receptor antagonist, candesartan cilexetil, and a vasodilator, hydralazine, were also examined. Results: Semiquantitative immunohistochemical evaluation and Western blot analysis showed that AII significantly enhanced glomerular expression of SMemb (0.87 ± 0.33 vs. 0.40 ± 0.19 for immunohistochemical grading, p < 0.05; 2.55 ± 0.88 vs. 1.16 ± 0.75 for Western blot analysis, p < 0.05). Glomerular fibronectin was also increased in AII-administered rats (301.7 ± 206.8 ng/5 µg protein vs. 95.8 ± 81.3 ng/5 µg protein, p < 0.05). Candesartan cilexetil attenuated these effects. On the other hand, hydralazine did not change the glomerular expression of SMemb enhanced by AII administration. Conclusion: All induced a phenotypic alteration in mesangial cells, enhanced the mesangial expression of SMemb and stimulated the fibronectin synthesis. These results suggest that the mesangial expression of SMemb is related to glomerular matrix accumulation and that AII mediates both mesangial processes via AT1 receptors.

To characterize the phenotypic alteration in mesangial cells in human glomerulonephritis, we investigated the expression of nonmuscle-type myosin heavy chain, SMemb, and alpha-smooth muscle actin (alpha-SM actin) in IgA nephropathy. The expression of SMemb and alpha-SM actin was examined by immunohistochemistry in biopsy specimens from 45 patients with IgA nephropathy. We examined a total of 489 glomeruli representing all patients enrolled, and found that mesangial expression of SMemb and alpha-SM actin was associated with mesangial proliferation. Only mesangial expression of SMemb showed a significant relationship with mesangial matrix accumulation. Semiquantitative evaluation using composite expression scores showed that the expression of SMemb was elevated in the patients with poor renal prognosis. The expression of alpha-SM actin showed no significant relationship with renal prognosis. These results suggest that mesangial expression of SMemb is an important factor in the progression of IgA nephropathy, and that SMemb and alpha-SM actin are associated with the activation of mesangial cells by different mechanisms.