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AbstractBackground/Aim: Prolonged exposure to hyperglycemia is one of the key factors to induce progressive diabetic nephropathy in humans. We examined whether or not the same phenomenon is observed in a nonobese type 2 diabetes model, in Goto-Kakizaki (GK) rats. Methods: Urine and serum samples from GK and Wistar rats were collected to measure biochemical parameters of the renal function. The kidneys of these animals were histopathologically and immunohistochemically analyzed. Results: Moderate hyperglycemia was sustained in GK rats during the experimental period. Noticeable morphological changes in the kidneys such as segmental glomerulosclerosis and tubulointerstitial fibrosis were observed only at 24 months of age. The expression of alpha smooth muscle actin and type IV collagen in glomeruli and tubulointerstitium was increased at 12 months of age and later. The macrophage infiltration was increased in parallel with the progression of renal lesions. The excretion of urinary protein in GK rats was increased only at 24 months of age. Moreover, the functional and morphological changes in Wistar rats were less severe than in age-matched GK rats. Conclusions: We conclude that renal changes of GK rats at a late stage were similar to those of progressive human diabetic nephropathy and that prolonged hyperglycemia may play a more crucial role in inducing progressive diabetic nephropathy than aging and obesity.Copyright © 2003 S. Karger AG, Basel

Acute hemodynamic effects of beraprost sodium were tested in a canine vasoconstrictive pulmonary hypertension model induced by the continuous infusion of U-46619, a thromboxane A2mimetic. The effects of beraprost were compared with those of prostaglandin E1, nitroglycerin and nifedipine. Beraprost and nitroglycerin decreased pulmonary arterial pressure. On the other hand, prostaglandin E1and nifedipine increased pulmonary arterial pressure. All drugs except nitroglycerin increased cardiac output and decreased pulmonary vascular resistance. Beraprost was selective to pulmonary circulation, while nitroglycerin, prostaglandin E1, and nifedipine showed poor selectivity for the pulmonary vasculature. These results suggest that the vasodilative effect of beraprost is the most selective for the pulmonary circulation among these four vasodilators.

To investigate the role of the serotonergic nervous system in blood pressure regulation, 5μg of 5-hydroxytryptamine (5-HT) was given i.c.v. before and after 1 μg of i.c.v. xylamidine or 200μg of i.c.v. ketanserin or 200μg of i.v. ketanserin in conscious Wistar Kyoto rats. Also i.v. (0.5, 1, 2μg) or i.c.v. (1μg) phenylephrine (PHE) were given before and after 1μg of i.c.v. xyla-midine. I.c.v. 5-HT elicited a consistent pressor response of approximately 27mHg and slight decrease in heart rate. MAP and heart rate did not change after xylamidine or ketanserin. Whereas pressor response to i.c.v. 5-HT after i.c.v. ketanserin or i.c.v. xylamidine was suppressed, it did not change after i.v. ketanserin. Neither i.c.v. nor i.v. PHE-induced pressor response was influenced by i.c.v. xylamidine pretreatment. These data suggest that the central 5-HT2 receptor may subserve pressor function in rats.