In the light of increasing evidence that benign prostatic hyperplasia is associated with cardiovascular disease, we have investigated the relationship between prostatic blood flow and prostatic hyperplasia in the spontaneously-hypertensive-rat (SHR). Twelve-week-old male SHRs were treated with nicorandil for six weeks. Wistar-Kyoto rats were used as controls. Six weeks after nicorandil treatment, blood pressure and the prostatic blood flow were estimated, and tissue levels of malondialdehyde, HIF-1α, TGF-β1, bFGF, dihydrotestosterone, and α-SMA were measured. SHRs showed significant increases in blood pressure, tissue levels of malondialdehyde, HIF-1α, TGF-β1, bFGF, α-SMA and a significant decrease in the prostatic blood flow. Although treatment with nicorandil failed to alter the blood-pressure and α-SMA, it significantly ameliorated the increased levels of malondialdehyde, HIF-1α, TGF-β1, and bFGF. There were no significant differences in tissue levels of dihydrotestosterone among any groups. These data indicate that development of prostatic hyperplasia may be associated with prostatic hypoxia, which nicorandil prevents via its effect to increase the blood flow.

These results indicate that N-hexacosanol has a beneficial effect on hyperreactivity in the diabetic detrusor by ameliorating overexpression of muscarinic M(2) and M(3) receptor mRNAs.

BACKGROUND AND PURPOSENicorandil, an ATP-sensitive potassium (KATP) channel opener and nitric oxide donor, is used in the treatment of angina and acute heart failure. Here we investigated the effects of two KATP channel openers, nicorandil and cromakalim on ischaemia reperfusion (I-R) injury in the kidney. EXPERIMENTAL APPROACHRight nephrectomy was performed in 8-week-old male Sprague-Dawley rats and they were then divided into six groups: control group; I-R, including 30 min of left renal ischaemia followed by 24 h of reperfusion; I-R groups plus nicorandil 3 or 10 mg·kg -1 i.p.; and I-R groups plus cromakalim 100 or 300 mg·kg -1 i.p. After reperfusion, renal function was estimated by serum creatinine (SCr), urinary albumin : creatinine ratio (ACR) and urinary b2-microglobulin (b2-MG). Levels of KATP channel subtypes were investigated by Western blot. Kidney sections were stained for 4-hydroxy-2-nonenal and 8-hydroxy-2′-deoxyguanosine. KEY RESULTSRenal I-R induced significant increases in SCr, ACR and b2-MG levels compared with the control animals. Treatment with KATP channel openers reduced urinary b2-MG levels, raised by I-R. Both KIR6.1 and KIR6.2 channels were expressed. Expression of KIR6.2 channels in the I-R group was lower than in the control group, which was restored to normal by treatment with KATP channel openers. Histologically, severe acute tubular damage was observed in the I-R kidney and this damage was ameliorated by KATP channel openers, dose-dependently. CONCLUSIONS AND IMPLICATIONSATP-sensitive potassium channel openers protected against proximal tubule damage after I-R injury. Nicorandil could represent a powerful additional component in the treatment of patients undergoing partial nephrectomy or renal transplantation. Abbreviations4-HNE, 4-hydroxy-2-nonenal; 8-OHdG, 8-hydroxy-2′-deoxyguanosine; CKD, chronic kidney disease; ELISA, enzyme-linked immunosorbent assay; IPreC, ischaemic preconditioning; I-R, ischaemia-reperfusion; KATP channel, ATP-sensitive potassium channel; OSOM, outer stripe of outer medulla; PAS, periodic acid-Schiff; ROS, reactive oxygen species; b2-MG, b2-microglobulin

time simultaneously with a laser Doppler flowmeter and an NO-selective electrode, respectively. After death the tissue levels of NO 2 -NO 3 (a marker of NO production), malondialdehyde (a marker of lipid peroxidation), 8-hydroxydeoxyguanosine (a marker of oxidative DNA damage), myeloperoxidase (a marker of neutrophil infiltration), and heat-shock protein 70 (HSP 70) and its mRNA were measured. The testicular tissue was also analysed histologically. RESULTSClamping the testicular artery resulted in a decrease of blood flow to 0-5% of the basal level measured before clamping. NO release was increased during clamping and gradually recovered to the basal level on removing the clip. Interestingly, the peak of NO release in rats of the no-drug group occurred at the start of reperfusion, while that in the high-dose drug group occurred several minutes later. The levels of NO 2 -NO 3 , malondialdehyde, 8-hydroxydeoxyguanosine, myeloperoxidase and HSP 70 and its mRNA, and histological variables, were significantly greater in the no-drug I-R group than in the control, and these variables were ameliorated by treatment with edaravone. CONCLUSIONThese results indicate that edaravone reduces the oxidative stress and prevents the testicular damage induced by I-R.

30 min and then the bladder was allowed to drain with a catheter in place for 60 min as the studies continued. After killing the rats the function of the bladder was assessed, with carbachol and 100 m M KCl, and the levels of malondialdehyde (MDA, a marker of lipid peroxidation), 8-hydroxydeoxyguanosine (8-OHdG; a marker of oxidative DNA damage), heat-shock protein 70 (HSP 70) and its mRNA were measured. RESULTSAUR increased the intravesical pressure and decreased blood flow, and subsequent catheterization decreased the intravesical pressure and increased blood flow. Edaravone induced a decrease in blood flow in the bladder during the urinary retention and subsequent catheterization compared to the blood flow in the AUR group. Edaravone resulted in protection of the contractile responses to both carbachol and KCl in a dose-dependent manner. The MDA concentration, 8-OHdG content and expressions of HSP-70 and its mRNA in the AUR group were significantly larger than those of the control group. Edaravone markedly suppressed the accumulations of MDA and 8-OHdG in the bladder, and reduced the expressions of HSP 70 and its mRNA. CONCLUSIONThese results indicate that edaravone reduces the oxidative stress and prevents the bladder dysfunction caused by AUR and subsequent catheterization.