We determined the renal responses to anaphylaxis and the effects of a nitric oxide synthesis inhibitor, L-NAME, in anesthetized rats and isolated perfused rat kidneys. After the ovalbumin antigen injection, the sensitized rats showed transient and substantial decreases in mean blood pressure and renal blood flow and an increase in renal vascular resistance. Creatinine clearance, a measure of renal function, decreased to 53% baseline at 2 h after antigen. L-NAME pretreatment significantly enhanced the antigen-induced renal vasoconstriction and renal dysfunction. Moreover, plasma creatinine levels significantly increased only in the L-NAME pretreated rats. Separately, in isolated perfused kidneys, we observed the antigen-induced renal vasoconstriction and its augmentation by L-NAME. In conclusion, the renal vascular response to the antigen is vasoconstriction, which is enhanced by L-NAME in both isolated perfused rat kidneys and anesthetized rats; it is accompanied by renal dysfunction, which is also augmented by L-NAME.

Arteriovenous fistula puncture pain is a serious problem for patients undergoing dialysis and a good indication for topical anesthetics. No previous study has compared lidocaine/prilocaine cream (EMLA) with lidocaine tape for pain relief during arteriovenous fistula puncture in patients undergoing maintenance hemodialysis. To this end, we conducted a multicenter randomized crossover study including 66 patients (mean age, 65.8 years; males, 57.6%) undergoing maintenance hemodialysis thrice/week. Subjects were assigned to Sequence EL (EMLA administration followed by lidocaine, with 1-week wash-out) or Sequence LE (reverse administration, first lidocaine then EMLA). All subjects completed the study. At each puncture site, 1 g EMLA (25 mg lidocaine + 25 mg prilocaine) or one sheet of lidocaine tape (18 mg lidocaine) was applied 1 h or 30 min prior to arteriovenous fistula puncture, respectively. The primary endpoint was puncture pain relief, which was measured using a 100-mm visual analog scale. The secondary endpoints included quality of life, which was measured by SF-36, and safety. EMLA produced a 10.1-mm greater visual analog scale improvement than lidocaine tape (P = 0.00001). However, there was no statistically significant difference in the quality of life between the two groups, and no significant carryover/period effect was observed in any analysis. Further, no drug-related adverse events were observed. Taken together, these results suggest that EMLA cream is superior to lidocaine tape for the relief of arteriovenous fistula puncture pain in patients undergoing maintenance hemodialysis.

Our findings suggest that the long-term RT induces DSBs and HRGEc-secreted COL type VI accumulation in the glomerular capillaries, which might progress to intractable glomerular fibrosis.

The rates of change per year in the median eGFR (ΔeGFR) and sHLA-G5 were -1.5 ml/min/1.73 m/year and 11.8 ng/ml, respectively. A positive correlation was detected between the ΔeGFR and sHLA-G5 (r = 0.188, p = 0.025). In multivariate regression analysis, sHLA-G5 and HLA-matching were significant predictors of an improvement in eGFR (beta for sHLA-G: 0.374, p = 0.009; beta for mismatching: -1.135, p = 0.045). The renal tubular epithelial cells (TEC) in 11 cases showed a perinuclear HLA-G1/5 expression after renal transplantation. The renal HLA-G1/5-positive patients displayed much better ΔeGFR (p < 0.05). In conclusion, the sHLA-G5 level and HLA matching status are independent predictors of renal allograft function, as determined by the ΔeGFR, in Japanese patients. HLA-G1/5 was also detected on TEC in the patients with favorable renal function.

Lung allergic diseases sometimes accompany pulmonary vaso-and broncho-constriction. Rats are currently used for the experimental study of lung allergies. However, their hemodynamic mechanisms are not fully understood. Therefore the effects of allergic mediators were determined systematically in vivo in rats in terms of pulmonary vascular resistance (PVR), airway pressure (AWP) and total peripheral resistance (TPR). We directly measured pulmonary arterial pressure, left atrial pressure, systemic arterial pressure, central venous pressure and aortic blood flow to determine PVR and TPR, as well as AWP, following injections of platelet-activating factor (PAF), histamine, serotonin, leukotriene (LT) C 4 , and prostaglandin (PG) D 2 in anesthetized open-chest artificially ventilated Sprague-Dawley (SD) rats. PVR was dose-dependently increased by consecutive administration of PAF, LTC 4 , and PGD 2 , with the maximal responsiveness being PAF>LTC 4 >PGD 2 . However, neither histamine nor serotonin changed PVR. TPR was decreased by all agents except LTC 4 which actually increased it. PAF and serotonin, but not the other agents, increased AWP. In conclusion, allergic mediators exert non-uniform actions on pulmonary and systemic circulation and airways in anesthetized SD rats: PAF, LTC 4 and PGD 2 , but not histamine or serotonin, caused substantial pulmonary vasoconstriction; LTC 4 yielded systemic vasoconstriction, while the others caused systemic vasodilatation; only two mediators, PAF and serotonin, induce airway constriction.Key words peripheral resistance; pulmonary arterial pressure; anaphylaxis; left atrial pressure; vasodilation; pulmonary vasoconstriction Rats are currently used for investigations on pulmonary allergic diseases.1-4) However, the studies on physiological characteristics of the rat pulmonary circulation were limited. The rat pulmonary vascular responses to various endogenous allergic mediators were previously examined in isolated perfused lungs [5][6][7] : platelet-activating factor (PAF) and leukotriene (LT) C 4 cause substantial vasoconstriction. In rat isolated pulmonary arteries, 8,9) serotonin showed strong constriction. However, there is no systematic study in which the effects of allergic mediators on the rat pulmonary vascular resistance (PVR) and total peripheral resistance (TPR) were determined by measuring cardiac output (CO) and the inflow and outflow pressures of the systemic and pulmonary circulations. Therefore, we measured directly and continuously CO, pulmonary arterial pressure (PAP) and left atrial pressure (LAP), along with systemic arterial pressure (SAP) and central venous pressure (CVP), in order to determine the responses of PVR and TPR to allergic mediators including PAF, histamine, serotonin, LTC 4 , and prostaglandin (PG) D 2 in anesthetized Sprague-Dawley (SD) rats. Airway pressure (AWP) was also measured to determine whether the allergic mediators cause bronchoconstriction. We hypothesized that these mediators do not exert the same directional actions on pulmonary and s...