Differential Effects of Angiotensin II on Intra-Renal Hemodynamics in Rats;Contribution of Prostanoids, NO and K⁺Channels

Many agents are known to cause qualitative and quantitative differences in intrarenal blood flow. This study tested the hypothesis that angiotensin II (AII) evokes a differential effect on cortical (CBF) and medullary blood flow (MBF) and that AT2 receptor mediates AII-induced increase in renal MBF by mechanisms related to nitric oxide (NO) and prostanoids. AII (100, 300 and 1000 ng/kg/min) increased mean arterial blood pressure (MABP) by 24% ± 7% (p G nitro-L-arginine (L-NNA), an inhibitor of NO synthase (100 mg/L in drinking water) enhanced AII effects on MABP (169 ± 75, p ATP channel blocker, did not affect intra-renal hemodynamics elicited by AII. Blockade of AT2 receptors with PD123319 (50 μg/kg/min) did not change basal or AII-induced changes MABP or CBF but blunted AII-induced increase in MBF by 60% ± 11 % (p 2 receptor agonist, elicited a reduction in MABP and increases in CBF and MBF that were abolished or attenuated by PD123319. These findings demonstrate that AII elicited differential changes in intrarenal blood flow;an AT1-mediated reduction in CBF but an AT2-mediated increase in MBF. The AT2 receptor-mediated increase in MBF involves guanylase cyclase, NO and dilator prostanoids but not KATP channels.

A new method for introduction ω-side chain of prostanoid using Barton radical reaction

A new method for introduction to-side chain of prostanoid was described in this note. Starting from acid chloride （3）, via Barton radical reaction, a trans α,β-unsaturated ketone sython was introduced.

A MILD AND REGIOSPECIFIC OXIRANE RING OPENING TO PRECURSORS FOR PROSTANOID CONGENERS

A stereoselective and regiospecific synthesis of procursors(2),(4),(6)and(7)of prostacyclin analogues from 2,3-epoxylbicyclo[3.2.0]hept-6-one(1)are described.

Investigations on the Significance of Inductable Cyclooxygenase in Atherogenesis in Cholesterol-Fed Rabbits

Atherosclerosis is the most prevalent disease in middle and later years of human life. Heart attacks and strokes are among the most frequent causes of death. New approaches in therapy are the use of NSAID’s (nonsteroidal antiphlogistical drugs) of the new generation (selective inhibitors of COX-2) and DHEA (Dehydroepiandrostenon). The key enzyme of prostaglandin synthesis, the COX-2 isoenzyme, is predominantly found in inflammatory tissue. Out of this results a possible importance of COX-2-inhibitors in prophylaxis of atherosclerosis. Our study intended to examine the significance of COX-2 and the COX-2-formed prostanoids, as well as the significance of COX-2-independent iso-prostanes on atherosclerosis. For that purpose we tested the effect of the selective COX-2-inhibitor Celecoxib on rabbits fed with cholesterol and compared this with the effect of the steroid hormone DHEA in 4 groups: healthy control, cholesterol-fed control, DHEA-group and Celecoxib group. In the test prostanoids, nitrate and nitrite were measured by gas chromatograpy/tandem-mass-spectrometry (GC-MS/MS) in 24-hours-collected urine. Additionally we measured cholesterol and triglycerides in plasma. The aortas of the examinated animals were measured optically using a planimetrical method. The measurement of prostanoids, isoprostanes, nitrate and nitrite showed considerable variations and particulary significant differences (p < 0.01) even in the initial values. By the treatment with Celecoxib the rate of atherosclerosis was reduced in a highly significant way in comparison to the cholesterol group and the DHEA-group. Consequently the test demonstrated a significant role of COX-2 in the development of atherogenesis.

The role of cyclooxygenase-2/prostanoid pathway in visceral pain induced liver stress response in rats

Background Cyclooxygenase （COX） is the rate-limiting enzyme in the production of prostanoids from arachidonic acid. COX-2 is the inducible enzyme in the COX family, together with the prostanoids forms the COX-2/prostanoid pathway. Research showed that the COX-2/prostanoid pathway is activated in hepatic diseases and liver stress reaction, such as fibrogenesis, portal hypertension, carcinogenesis, and ischemic/repeffusion injury. But there was no report on visceral pain induced liver stress. This study was to investigate the role of the COX-2/prostanoid pathway in liver stress response in rat acute colitis visceral pain liver stress model.Methods Fifty-three male SD rats were randomly divided into Naive, Model, NS398 treatment, and Morphine treatment groups. The rat acute colitis visceral pain liver stress model was established under anesthesia by the colonic administration of 0.5 ml of 6% acetic acid using a urethral catheter. NS398 and morphine were administrated 30 minutes prior to model establishment in NS398 and Morphine treatment groups respectively. Spontaneous activities and pain behavior were counted and the extent of colonic inflammation was assessed histologically. Liver tissue levels of Glutathione-S-Transferase （GST） activity, COX-2 mRNA, prostaglandin E2 （PGE2）, thromboxane B2 （TXB2） and 6-Ketone-prostaglandin F1α （6-K-PGF1α） contents were assessed.Results Thirty minutes after the colonic administration of acetic acid, a significant decrease in spontaneous activities and an increase in pain behaviors were observed in Model group （P〈0.01 and P〈0.05 respectively）, accompanied by colonic inflammation. Liver GST activity levels significantly dropped （P〈0.05）. Liver COX-2 mRNA expressi.on significantly increased, accompanied by an increase in liver concentrations of PGE2 and TXB2, but no obvious change in 6-K-PGF1α concentrations. NS398 and morphine both ameliorated post-stress liver GST activity （P〈0.05 and P〈0.01 respectively）, decreased stress-induced COX-2 expression, decreased PGE2 and TXB2 production, but increased liver 6-K-PGF1α levels. Morphine attenuation in colonic tissue inflammation was apparent at 24 hours （P〈0.05）.Conclusions Acute colitis visceral pain liver stress can induce liver injury. Liver injury might have occurred through the activation of the COX-2/prostanoid pathway and increased production of PGE2 and TXB2. Effective analgesia might offer protective effect during visceral pain stress.

Cyclooxygenase-2 and Decidual Immune Cells

Cyclooxygenase-2(COX-2)is a rate-limiting enzyme in arachidonic acid(AA)metabolism.COX-2 and its products(prostanoids)serve versatile biological functions during pregnancy.Numerous evidences demonstrate special reprogramming of COX-2-catalyzing AA metabolism in decidual immune cells(DICs),particularly in decidual macrophages,corresponding to special gestational phases.This review summarizes the reprogramming of COX-2-catalyzing AA metabolism in DICs as well as the immunoregulation of diverse COX-2-generating prostanoids in DICs during the different phases of gestation.