Background To date, there have been no reports on altered nitric oxide （NO） content in ischemia/reperfusion with regard to in vivo preconditioning procedures. These studies are important for understanding the mechan...Background To date, there have been no reports on altered nitric oxide （NO） content in ischemia/reperfusion with regard to in vivo preconditioning procedures. These studies are important for understanding the mechanisms of NO during early myocardial ischemic preconditioning. The aim of the present study was to investigate the mechanisms of NO during early myocardial ischemic preconditioning by measuring levels of NO and cyclic guanosine monophosphate （cGMP）, as well as activity of nitric oxide synthase （NOS） in ischemia/reperfusion with respect to preconditioning in rats. Methods Sixty-six female Sprague-Dawley rats were randomly divided into four groups： ischemic preconditioning group （IP）, ischemia/reperfusion group （I/R）, control group （CON）, and preconditioning procedure group （PC）. In the PC group, rats were further divided into PC1-, PC1＋, PC2-, PC2＋, PC3-, and PC3＋ subgroups. Rats underwent left coronary artery occlusion and reperfusion, and subsequently, NOS activity and levels were assessed with spectrophotometric analysis. cGMP contents were measured with radioimmunoassay. Results The level of NO and cGMP, as well as the activity of NOS, were significantly higher in the IP group compared to the I/R and CON groups （P 〈0.05）. During preconditioning prior to prolonged ischemia, NO and cGMP levels varied markedly with ischemia and reperfusion. The levels of NO repeatedly increased when the heart was exposed to three episodes of 5-minute ischemia, and were almost completely reversed during each reperfusion period. NO and cGMP levels were significantly different between the 5-minute period of ischemia and the same period of reperfusion during preconditioning. Conclusions NO plays an important role during early phase myocardial ischemic preconditioning in rats. NO and cGMP could be triggers and mediators of early phase myocardial ischemic preconditioning. Altered NOS activity following ischemic stress could be the primary inducer of higher NO levels detected. NO and cG展开更多
Erectile dysfunction （ED） associated with type 2 diabetes is a severe problem that requires effective treatment. Pancreatic kininogenase （PK） has the potential to improve the erectile function of ED patients. This...Erectile dysfunction （ED） associated with type 2 diabetes is a severe problem that requires effective treatment. Pancreatic kininogenase （PK） has the potential to improve the erectile function of ED patients. This study aims to investigate the effect of PK on erectile function in streptozotocin-induced type 2 diabetic ED rats. To achieve this goal, we divided male Sprague-Dawley rats into five groups. One group was not treated, and the other four groups were treated with saline, sildenafil, PK or sildenafil, and PK, respectively, for 4 weeks after the induction of type 2 diabetic ED. Then, intracavernous pressure under cavernous nerve stimulation was measured, and penile tissue was collected for further study. Endothelial nitric oxide synthase levels, smooth muscle content, endothelium content, cyclic guanosine monophosphate （cGMP） levels in the corpus cavernosum, and neuronal nitric oxide synthase levels in the dorsal penile nerve were measured. Improved erectile function and endothelium and smooth muscle content in the corpus cavernosum were observed in diabetic ED rats. When treating diabetic ED rats with PK and sildenafil at the same time, a better therapeutic effect was achieved. These data demonstrate that intraperitoneal injection of PK can improve erectile function in a rat model of type 2 diabetic ED. With further research on specific mechanisms of erectile function improvement, PK may become a novel treatment for diabetic ED.展开更多
Aim： To further investigate the relaxation mechanism of neferine （NED, a bis-benzylisoquinoline alkaloid extracted （isolated） from the green seed embryo of Nelumbo nucifera Gaertn in China, on rabbit corpus cavern...Aim： To further investigate the relaxation mechanism of neferine （NED, a bis-benzylisoquinoline alkaloid extracted （isolated） from the green seed embryo of Nelumbo nucifera Gaertn in China, on rabbit corpus cavernosum tissue in vitro. Methods： The effects of Nef on the concentrations of cyclic adenosine monophosphate （cAMP） and cyclic guanosine monophosphate （cGMP） in isolated and incubated rabbit corpus cavernosum tissue were recorded using ^125I radioimmunoassay. Results： The basal concentration of cAMP in corpus cavernosum tissue was 5.67 ± 0.97 pmol/mg. Nef increased the cAMP concentration in a dose-dependent manner （P 〈 0.05）, but this effect was not inhibited by an adenylate cyclase inhibitor （cis-N-[2-phenylcyclopentyl]azacyclotridec-1-en-2-amine, MDL-12, 330A） （P 〉 0.05）. The accumulation of cAMP induced by prostaglandin Et （PGEt, a stimulator of cAMP production） was also augmented by Nef in a dose-dependent manner （P 〈 0.05）. The basal concentration of cGMP in corpus cavernosum tissue is 0.44 ± 0.09 pmol/mg. Nef did not affect this concentration of cGMP, either in the presence or in the absence of a guanyl cyclase inhibitor （1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, ODQ） （P 〉 0.05）. Also, sodium nitroprusside （SNP, a stimulator of cGMP production）-induced cGMP production was not enhanced by Nef （P 〉 0.05）. Conclusion： Nef, with its relaxation mechanism, can enhance the concentration of cAMP in rabbit corpus cavernosum tissue, probably by inhibiting phosphodiesterase activity. （Asian JAndro12008 Mar; 10： 307-312）展开更多
文摘Background To date, there have been no reports on altered nitric oxide （NO） content in ischemia/reperfusion with regard to in vivo preconditioning procedures. These studies are important for understanding the mechanisms of NO during early myocardial ischemic preconditioning. The aim of the present study was to investigate the mechanisms of NO during early myocardial ischemic preconditioning by measuring levels of NO and cyclic guanosine monophosphate （cGMP）, as well as activity of nitric oxide synthase （NOS） in ischemia/reperfusion with respect to preconditioning in rats. Methods Sixty-six female Sprague-Dawley rats were randomly divided into four groups： ischemic preconditioning group （IP）, ischemia/reperfusion group （I/R）, control group （CON）, and preconditioning procedure group （PC）. In the PC group, rats were further divided into PC1-, PC1＋, PC2-, PC2＋, PC3-, and PC3＋ subgroups. Rats underwent left coronary artery occlusion and reperfusion, and subsequently, NOS activity and levels were assessed with spectrophotometric analysis. cGMP contents were measured with radioimmunoassay. Results The level of NO and cGMP, as well as the activity of NOS, were significantly higher in the IP group compared to the I/R and CON groups （P 〈0.05）. During preconditioning prior to prolonged ischemia, NO and cGMP levels varied markedly with ischemia and reperfusion. The levels of NO repeatedly increased when the heart was exposed to three episodes of 5-minute ischemia, and were almost completely reversed during each reperfusion period. NO and cGMP levels were significantly different between the 5-minute period of ischemia and the same period of reperfusion during preconditioning. Conclusions NO plays an important role during early phase myocardial ischemic preconditioning in rats. NO and cGMP could be triggers and mediators of early phase myocardial ischemic preconditioning. Altered NOS activity following ischemic stress could be the primary inducer of higher NO levels detected. NO and cG
基金This work was supported by grants from the National Natural Science Foundation of China （No. 81571430, 81070485, and 81701433）.
文摘Erectile dysfunction （ED） associated with type 2 diabetes is a severe problem that requires effective treatment. Pancreatic kininogenase （PK） has the potential to improve the erectile function of ED patients. This study aims to investigate the effect of PK on erectile function in streptozotocin-induced type 2 diabetic ED rats. To achieve this goal, we divided male Sprague-Dawley rats into five groups. One group was not treated, and the other four groups were treated with saline, sildenafil, PK or sildenafil, and PK, respectively, for 4 weeks after the induction of type 2 diabetic ED. Then, intracavernous pressure under cavernous nerve stimulation was measured, and penile tissue was collected for further study. Endothelial nitric oxide synthase levels, smooth muscle content, endothelium content, cyclic guanosine monophosphate （cGMP） levels in the corpus cavernosum, and neuronal nitric oxide synthase levels in the dorsal penile nerve were measured. Improved erectile function and endothelium and smooth muscle content in the corpus cavernosum were observed in diabetic ED rats. When treating diabetic ED rats with PK and sildenafil at the same time, a better therapeutic effect was achieved. These data demonstrate that intraperitoneal injection of PK can improve erectile function in a rat model of type 2 diabetic ED. With further research on specific mechanisms of erectile function improvement, PK may become a novel treatment for diabetic ED.
基金Acknowledgment The authors thank Prof. Jia-Ling Wang for kindly supplying the neferine. The technical support from Prof. Bo-Hua Shu is also greatly appreciated. This study was sponsored by the National Natural Science Foundation of China （No. 30471736） and China Postdoctoral Science Foundation （No. 20070410176）.
文摘Aim： To further investigate the relaxation mechanism of neferine （NED, a bis-benzylisoquinoline alkaloid extracted （isolated） from the green seed embryo of Nelumbo nucifera Gaertn in China, on rabbit corpus cavernosum tissue in vitro. Methods： The effects of Nef on the concentrations of cyclic adenosine monophosphate （cAMP） and cyclic guanosine monophosphate （cGMP） in isolated and incubated rabbit corpus cavernosum tissue were recorded using ^125I radioimmunoassay. Results： The basal concentration of cAMP in corpus cavernosum tissue was 5.67 ± 0.97 pmol/mg. Nef increased the cAMP concentration in a dose-dependent manner （P 〈 0.05）, but this effect was not inhibited by an adenylate cyclase inhibitor （cis-N-[2-phenylcyclopentyl]azacyclotridec-1-en-2-amine, MDL-12, 330A） （P 〉 0.05）. The accumulation of cAMP induced by prostaglandin Et （PGEt, a stimulator of cAMP production） was also augmented by Nef in a dose-dependent manner （P 〈 0.05）. The basal concentration of cGMP in corpus cavernosum tissue is 0.44 ± 0.09 pmol/mg. Nef did not affect this concentration of cGMP, either in the presence or in the absence of a guanyl cyclase inhibitor （1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, ODQ） （P 〉 0.05）. Also, sodium nitroprusside （SNP, a stimulator of cGMP production）-induced cGMP production was not enhanced by Nef （P 〉 0.05）. Conclusion： Nef, with its relaxation mechanism, can enhance the concentration of cAMP in rabbit corpus cavernosum tissue, probably by inhibiting phosphodiesterase activity. （Asian JAndro12008 Mar; 10： 307-312）
