Warfarin reduces the incidence of osteonecrosis of the femoral head in spontaneously hypertensive rats.

In this study, we investigated the effects of warfarin potassium on the incidence of the femoral head osteonecrosis in spontaneously hypertensive rats (SHR). Twenty-four SHRs were divided into two equal groups, one given normal water (water group) and another provided with water containing warfarin (warfarin group). We compared the two groups histologically and observed the incidence of osteonecrosis. We also studied 17 Wistar Kyoto rats (WKY) to compare with SHR. Coagulation time, platelet count, and protein C activity were measured. Immunohistochemistry was also performed using endothelial nitric oxide synthetase (eNOS) antibody to investigate the function of endothelial cells. The incidence of osteonecrosis was significantly less in the warfarin group (10.5%) than in the water group (52.6%). Coagulation time was significantly longer in the warfarin group than the water group. Platelet count and protein C activity were not statistically different between the warfarin group and the water group. Results of immunohistochemistry revealed that endothelial cells in the femoral head were positive for eNOS in WKY but not in SHR. Our results indicated that warfarin reduced the incidence of femoral head necrosis in SHR.

5-Hydroxytryptamine receptors, especially the 5-HT4 receptor, in guinea pig urinary bladder.

The function of 5-hydroxytryptamine (5-HT) receptors, especially the 5-HT4 receptor, in the urinary bladder were examined in preparations isolated from the guinea pig by in vitro receptor autoradiography and determinations of mechanical activity and acetylcholine (ACh) release. Specific [125I]SB207710 binding sites were detected evenly throughout the urinary bladder. 5-HT (3 x 10(-8)-10(-4) M) caused contractions of strips of the urinary bladder, in a concentration dependent manner. Ketanserin antagonized the 5-HT-induced contractions, while granisetron and SB204070 antagonized the contractions induced by high concentrations of 5-HT. Atropine inhibited the contractions induced by high concentrations of 5-HT. Ketanserin prevented the 5-HT-induced contractions in the presence of atropine, but granisetron and SB204070 did not affect the contractions under such a condition. 5-HT enhanced the electrically-stimulated (5 Hz, 0.5 ms) outflow of [3H]acetylcholine from strips preloaded with [3H]choline, and the enhancement was antagonized by granisetron and SB204070. Thus, the contractile response to 5-HT was mediated by activations of 5-HT2, 5-HT3 and 5-HT4 receptors. The 5-HT2 receptor may be a property of high affinity to 5-HT and located on the smooth muscle cells. The 5-HT4 as well as 5-HT3 receptor may be a property of low affinity to 5-HT and located on the cholinergic neurons.