The influences of morpholin ring and perizine ring compounds on relaxation of rat aortic rings / 中国药理学通报

AIM Our investigation is to screen bioactive novel compounds using the isolated rat aortic rings and depending on the similar and distinct characteristics between the endothelial target for acetylcholine(ETA) and muscarinic receptors and to investigate the mechanisms of vasodilatory effects of candidate compounds. METHODSIn isolated rat aorta precontracted with NE, the vasodilatory effects of novel structure compounds were investigated. We Compared the maximal relaxation of endothelium denuded aorta with that of the endothelium intact aorta elicited by the 8 candidate compounds respectively. The aortas were precubated with L NAME, indomethacine and atropine before using NE, and measured the changes of the maximum vasodilatory rate of candidate compound. RESULTS AND CONCLUSION Among 81 compounds, we found 8 novel compounds which induced relaxation. Their maximal relaxation rates ranged of from 50 percent to 85 percent. The endothelium dependent relaxation induced by DMHPPP and PPVP was blocked by indomethacin and L NAME, but not by atropine. DMHPPP and PPVP also enhanced the maximal endothelium dependent relaxation induced by acetylcholine. These suggest that novel compounds may regulate functions of endothelial cell target for acetylcholine(ETA) to induce relaxation of isolated rat aortic rings, which may involve the prostacycline and nitric oxide pathways.

Effect of Oral Administration of Beraprost Sodium on Erectile Dysfunction / 대한비뇨기과학회지

PURPOSE: Beraprost Sodium (BPS) is an orally stable prostacyclin (PGI2) analogue and exerts an inhibitory effect on platelet aggregation as well as a potent vasodilatory effect. We investigated the efficacy and safety of BPS in patients with erectile dysfunction (ED). MATERIALS AND METHODS: A total of 74, consecutive patients subjected to have impotence work-ups including history taking, penile duplex ultrasonography, pharmacological erection test, and cavernous nicotinamide adenosine dinucleotide phosphatase (NADPH) diaphorase staining. Sixty-six patients continuously received BPS for more than 4weeks (range 4-32 weeks, average 8.4+/-5.8 weeks), bid or tid (a total 80-120microgram/day) for long-term control of ED. Remaining 8 patients intermittently received 40-60microgram of BPS an hour prior to intercourse to obtain immediate erection for on-demand treatment. Sexual function was compared by analysis of an International Index of Erectile Function (IIEF) and general efficacy based on patient's subjective evaluation after treatment. RESULTS: IIEFs of all patients were significantly improved after BPS treatment for ED. Erectile function with IIEF question No. 3 and 4 were improved by 1.7+/-1.3 to 3.2+/-1.8 and 1.4+/-0.9 to 2.7+/-1.6, respectively (p<0.05). General efficacy of BPS was shown as full effect in 23%, moderate effect in 31%, mild effect in 26%, and no effect in 20% of the patients. Better sexual function including IIEF and general efficacy were observed in continuous treatment group than on-demand treatment group. Better result was also found in diabetics than non-diabetics (p<0.05) while no difference was observed among psychogenic, vasculogenic, and neurogenic group. The side effect of BPS was minimal; flushing in 8%, headache in 5%, indigestion in 4%, and insomnia in 1% of total patients. CONCLUSIONS: Oral BPS is a safe and effective agent to treat ED. It remains to be investigative, to determine desirable treatment method and to elucidate long term control of ED in association with oral BPS.

Evaluation of Cerebrospinal Fluid Levels of Thromboxane B2 and 6-ketoprostaglandin F1alpha in Patients with Aneurysmal Subarachnoid Hemorrhage

In order to find out the relationship between arachidonic acid(AA) metabolites and the development of vasospasm following a subarachnoid hemorrhage(SAH), we evaluated the cerebrospinal fluid(CSF) levels of the two main AA metabolites, prostacyclin(PGI2) and thromboxane A2(TXAZ) by measuring their stable degredation products 6-keto-prostaglandin F1alpha(PGF1) and thromboxane B2(TXB2) using radioimmunoassay methods in 32 patients after an aneurysmal rupture and in 11 patients without an aneurysmal rupture as a control group. We compared the data between aneurysmal ruptured patients and control group patients. We also divided the data of the aneurysmal ruptured patients into 3 groups checking them between 1-4, 5-11, and 12-28 days after the SAH, and compared the data among the groups, then the data was also compared between non-vasospasm and clinical or severe angiographic vasospasm groups of patients. The results showed that the AA metabolism was enhanced after the SAH, The TXB2 increased the greatest amount in 1-4 days after the SAH and significantly decreased statistically 12 days after the SAH(p<0.002). This study also showed that the TXB2 level was significantly higher statistically in 1 to 4 days in the clinical or angiogrophically severe vasospasm group than in the non-vasospasm group of patients(p<0.032). PGF1 did not show any statistically significant changes according to the number of SAH days or a difference between the vasospasm and non-vasospasm groups. This result suggests if the AA metabolites are involved in the pathogenesis of cerebral vasospasm, and the lumbar CSF levels of AA metabolites in aneurysmal patients reflect the arterial synthesis of PGI2 and platelet origin of TXA2, the elevation of TXA2 or other vasoconstrictor prostaglandins is more likely to play a major role in the pathogenesis of vasospasm than PGI2 deficiency. The measurements of the CSF TXB2 in 1 to 4 days after a SAH may have an expectant value in the development of clinical or severe angiographic vasospasm(exclude the accompanying intraventricular hemorrhage patients).