Effect of prostaglandin E2 on the pressor response to periarterial stimulation and norepinephrine of the isolated perfused rabbit kidney.

The interaction of prostaglandin E2 (PGE2) and aspirin with the responses to peri-arterial stimulation (PS) and norepinephrine (NE) was studied in the isolated kidney of rabbit perfused through the renal artery at constant flow with Krebs' solution. NE and PS increased vascular perfusion pressure of kidney and caused a contraction on the isolated rabbit aortic strip superfused with the effluent from kidney. Addition of PGE2 to the perfusion medium decreased the PS-induced rise in perfusion pressure without changing the effect of exogenous NE. In contrast, addition of aspirin to the perfusion medium induced a potentiation of the response to PS but not to NE. These results suggest that PGE2 modulates the effect of PS probably by inhibiting the releases of NE from sympathetic nerve endings.     

Effect of diarachidonin on prostaglandin E2 synthesis in rabbit kidney medulla slices.

The effect of diarachidonin on the synthesis of prostaglandin E2 in rabbit kidney medulla slices was examined. The addition of diarachidonin stimulated prostaglandin E2 production in a dose-dependent manner. At three concentrations (10, 50 and 100 microM), increases in prostaglandin E2 formation induced by exogenous diarachidonin were 2-fold greater than those induced by exogenous arachidonic acid. Diacylglycerol or phosphatidic acid from egg lecithin had little or no effect on prostaglandin E2 production. Moreover, EGTA failed to inhibit diarachidonin-stimulated prostaglandin E2 formation, indicating that the stimulatory effect of diarachidonin is not mediated through the activation of endogenous phospholipase A2 (including phosphatidic acid-specific phospholipase A2). These results are discussed in the light of our former hypothesis that arachidonic acid release from kidney medulla phospholipids might occur through the sequential action of a phospholipase C coupled to diacylglycerol and monoacylglycerol lipases [Fujimoto, Akamatsu, Hattori & Fujita (1984) Biochem. J. 218, 69-74].     

Placental vascular response to prostaglandin I2 in the rabbit

We have tested the hypothesis that the maternal placental refractoriness to prostaglandin I2 in the sheep is a species specific response by observing the response of the maternal placental vasculature of near-term rabbits to exogenous prostaglandin I2 infused at 10 micrograms/min for 5 min. Regional blood flows were measured with radioactive microspheres. Observations were made during the infusion of vehicle (control) and after 5 min of prostaglandin I2 infusion. The experiment was then repeated using microspheres of a different size. Fifteen and 25 mu spheres were used. If the same answer were obtained with both sphere sizes we would be confident that the result was not an artifact of shunted spheres. Seven rabbits were used in this study. The control (15 micron) blood pressure was 68 +/- 4 mmHg and prostaglandin I2 resulted in a depression of the pressure to 41 +/- 3 mmHg (P less than 0.001). The renal vascular resistance was 19.2 +/- 2.1 mmHg.ml-1.min. g in the control (15 micron) condition and 9.7 +/- 1.0 mmHg.ml-1.min.g after prostaglandin I2 (P less than 0.002). Prostaglandin I2 acted as a vasodilator in this organ as would be expected. The nonplacental uterine tissue had a control (15 micron) resistance of 624 +/- 125 and 612 +/- 184 mmHg.ml-1.min.g after prostaglandin I2 (NS). Using 25 mu spheres the results were 383 +/- 28 and 341 +/- 44 mmHg.ml-1.min.g respectively (NS). Shunting was observed in this organ but the direction of the responses to prostaglandin I2 was not affected.(ABSTRACT TRUNCATED AT 250 WORDS)     

In vitro electrophysiological effects of cimetidine, prostaglandin E2 and acetylcholine on the rabbit gastric mucosa

The electrophysiological effects of cimetidine, cytoprotective dose of prostaglandin E2 (PGE2) and acetylcholine were determined in parallel in Ussing-chambered rabbit fundic and antral mucosal preparations. In the fundic mucosal preparations both cimetidine and PGE2 caused an increase in transmucosal potential difference (PD) and in short-circuit current (ISC); the transepithelial resistance (Rt) was essentially unchanged. Addition of acetylcholine to the pretreated fundic preparations produced further gradual increases in PD and ISC; cimetidine pretreatment delayed this effect of acetylcholine. In contrast to fundic mucosa, cimetidine did not cause any electrical change of the antral preparation but decreases in PD, Rt and ISC were detected after the addition of PGE2. Acetylcholine produced a rapid initial PD elevation followed by a PD drop of both antral tissues independent of pretreatment. These findings suggest that both cimetidine and PGE2 generated electrical hyperpolarisation of rabbit fundic mucosa. These changes may be favourable for mucosal protection. No "beneficial" electrical changes were detected on the antral mucosa after administration of cimetidine and PGE2. Acetylcholine increased the effects of other stimuli on the fundic mucosa. In the rabbit antral mucosa acetylcholine generated biphasic changes of electrical properties.     

Changes induced by angiotensins and prostaglandin E2 on the release of transmitter from isolated perfused rabbit kidney during periarterial stimulation.

The influence of A II and PGE2 on the rise of perfusion pressure induced by periarterial stimulation and NA were studied in the rabbit isolated perfused kidney. Periarterial stimulation produced an increase in perfusion pressure and the venous outflow superfusing the rabbit aortic strip caused the muscle to contract. Both effects were found to be frequency dependent. NA induced similar effect when given into the renal artery. A II and its N-terminal analogs produced equal potentiation to periarterial stimulation without altering the effect of exogenous NA when added to the perfusion medium. DMGIA II which is a competitive inhibitor of A II inhibited the potentiating affect of A II. PGE2 also inhibited the effect of A II without altering the effect of exogenous NA. Addition of aspirin to the perfusion medium caused a potentiation to periarteral stimulation but did not change the effect of NA. A II added to the perfusion fluid containing aspirin still caused potentiation. From these results it was concluded that: (i) A II-induced potentiation to periarterial stimulation is mediated via specific receptors and probably due to facilitation of the release of transmitter from sympathetic nerve ending. (ii) PGE2 inhibited the release of transmitter. The effect of A II and PGE2 seemed to be mediated by independent mechanisms.     

Effect of prostaglandin E2on the pressor response to peri-arterial stimulation and norepinephrine of the isolated perfused rabbit kidney

The interaction of prostaglandin E₂ (PGE₂) and aspirin with the responses to peri-arterial stimulation (PS) and norepinephrine (NE) was studied in the isolated kidney of rabbit perfused through the renal artery at constant flow with Krebs' solution. NE and PS increased vascular perfusion pressure of kidney and caused a contraction on the isolated rabbit aortic strip superfused with the effluent from kidney. Addition of PGE₂ to the perfusion medium decreased the PS-induced rise in perfusion pressure without changing the effect of exogenous NE. In contrast, addition of aspirin to the perfusion medium induced a potentiation of the response to PS but not to NE. These results suggest that PGE₂ modulates the effect of PS probably by inhibiting the release of NE from sympathetic nerve endings.     

Azathioprine-induced in vitro inhibition of prostaglandin E2 production by rabbit retina

Although much work exists concerning the clinical and immunosuppressive effects of azathioprine, little is known of the mechanism of action of this drug. The present study reports that azathioprine at the concentrations of 0.1 and 0.05 micrograms/ml causes a significant suppression of in vitro prostaglandin E2 production by rabbit retinas. However, at concentrations below (0.01 microgram/ml) or above (1,10 micrograms/ml) azathioprine was not inhibitory effect. These results suggest a dose-dependent inhibitory effect of azathioprine on prostaglandin E2 production.     

Comparison of the effects of prostaglandin I2 and prostaglandin E2 stimulation of the rat kidney adenylate cyclase-cyclic AMP systems

Prostacyclin (Prostaglandin I₂) effects on the rat kidney adenylate cyclase-cyclic AMP system were examined. Prostaglandin I₂ and prostaglandin E₂, from 8 · 10^?4 to 8 · ^?7 M stimulated adenylate cyclase to a similar extent in cortex and outer medulla. In inner medulla, prostaglandin I₂ was more effective than prostaglandin E₂ at all concentrations tested. Both prostaglandin I₂ and prostaglandin E₂ were additive with antidiuretic hormone in outer and inner medulla. Prostaglandin I₂ and prostaglandin E₂ were not additive in any area of the kidney, indicating both were working by similar mechanisms. Prostaglandin I₂ stimulation of adenylate cyclase correlated with its ability to increase renal slice cyclic AMP content. Prostaglandin I₂ and prostaglandin E₂ (1.5 · 10^?4 M) elevated cyclic AMP content in cortex and outer medulla slices. In inner medulla, with Santoquin® (0.1 mM) present to suppress endogenous prostaglandin synthesis, prostaglandin I₂ and prostaglandin E₂ increased cyclic AMP content. 6-Ketoprostaglandin F_1α, the stable metabolite of prostaglandin I₂, did not increase adenylate cyclase activity or tissue cyclic AMP content. Thus, prostaglandin I₂ activates renal adenylate cyclase. This suggests that the physiological actions of prostaglandin I₂ may be mediated through the adenylate cyclase-cyclic AMP system.     

Angiotensin II potentiates responses of the rabbit basilar artery to adrenergic nerve stimulation

Angiotensin II has little contractile effect on the isolated rabbit basilar artery; however, it markedly potentiates contractile responses to adrenergic nerve stimulation. This is not a post-synaptic effect of angiotensin, as responses to exogenous norepinephrine are not altered. Angiotensin increases stimulation-evoked release of norepinephrine, and this effect probably accounts for the increased response to adrenergic nerve stimulation. Since sympathetic stimulation may protect the cerebral circulation from hypertensive damage, increased responsiveness to adrenergic nerve activity produced by angiotensin may have a beneficial effect.     

The influence of prostaglandin E2 and indomethacin on progesterone production and ovulation in the rabbit ovary perfused in vitro

The effects of prostaglandin E2 (PGE2) on the ovulation process were studied in a recirculating perfusion model using ovaries from virgin rabbits. Ovulation frequency, time of ovulation, and progesterone release from the ovaries were examined after the addition of PGE2, either alone or with luteinizing hormone (LH) in the presence or absence of indomethacin. The stimulatory effect of LH on ovulation was totally blocked if the ovaries were exposed to indomethacin at the same time. Ovaries treated with PGE2 alone did not ovulate, and PGE2 was unable to restore indomethacin-blocked ovulation. Conversely, the frequency of ovulation was reduced in ovaries treated with PGE2 and LH compared with controls receiving only LH. There was no measurable difference in the pattern of progesterone release between ovaries simultaneously treated with LH and indomethacin and LH-treated controls. Ovaries exposed to PGE2 alone showed only a slight increase of progesterone release in the medium, while those treated with PGE2 in combination with LH in the perfusate showed a smaller progesterone release than those treated with LH alone. The results confirm the blocking effect on ovulation by indomethacin. PGE2 could not reverse this effect, but instead reduced the number of LH-induced follicular ruptures. Indomethacin had no effect on progesterone levels, while PGE2 (which alone showed a slight stimulating effect on the steroid concentration) together with LH counteracted the effect of LH on progesterone release.     

Potentiation of bradykinin-induced vascular permeability increase by prostaglandin E2 and arachidonic acid in rabbit skin.

The activity of prostaglandins (PG) in producing vascular permeability was quantitated by dye extraction method in skin of anaesthetized rabbits. PGE1 and PGE2 (0.01-10 mug) produced increase in vascular permeability. Activity was approximately equal to that of histamine (Hist) and 1/20 of that of bradykinin (BK) on a weight basis. The activity of PGF1alpha and PGF2alpha was only 1/20 of that of PGE1 or PGE2. In spite of the relatively low potency of PGE1 and PGE2 in the rabbit, near threshold doses (0.1 or 1 mug) of PGE2 could potentiate permeability responses to bradykinin (0.1 mug) by 10 or 100-fold, respectively. Equivalent doses (0.1 or 1 mug) of histamine could not potentiate the bradykinin responses. Arachidonic acid (AA) at 1 mug, produced a 10-fold potentiation in the permeability response to bradykinin (0.1 mug). Pretreatment of the rabbits with indomethacin (20 mg/kg, i.p.) reduced the responses of BK (0.1 mug) + AA (1 mug) down to a similar magnitude of those seen with bradykinin alone. However, indomethacin did not block responses to either, BK alone, BK + PGE2, or BK + Hist. Various doses (1, 10, 100 and 300 mug) of arachidonic acid alone also produced increase in cutaneous vascular permeability, although its potency was only 1/3-1/8 of that of PGE2. This activity of arachidonic acid was attributed in part to its bioconversion to PGE2, since its activity was significantly reduced by the prostaglandin antagonist, diphloretin phosphate (DPP) (60 mg/kg, i.v.) and by indomethacin (20 mg/kg, i.p.), which blocks conversion of arachidonic acid to prostaglandins. Arachidonic acid may owe some of its permeability increasing effects to histamine release, since its effects were also reduced by the anti-histamine, pyrilamine (2.5 mg/kg, i.v.).     

Effect of the intra-aortic administration of prostaglandin E2 on kidney functions in acute kidney failure of blood transfusion origin

It has been shown that intraaortal prostaglandin E2 injection to dogs arrested acute renal failure of hemotransfusion genesis, which was expressed in normalization of minute and diurnal diuresis, glomerular filtration rate, tubular reabsorption, maximal tubular secretion, renal plasma flow, urea and creatinine levels. The data obtained serve as an experimental basis for prostaglandin E2 application in the treatment of acute renal failure.     

Stimulation of prostaglandin E2 synthesis by exogenous phospholipase A2 and C in rabbit kidney medulla slices.

We have investigated the effects of phospholipase A2 and C on the synthesis of prostaglandin E2 in rabbit kidney medulla and the release of fatty acids from the medulla slices. Exogenous phospholipase A2 [from Naja naja (Indian cobra) venom] and phospholipase C (from Clostridium welchii) stimulated prostaglandin E2 production in a dose-dependent manner. At the maximal effective concentrations (0.5 unit of phospholipase A2/ml, 2 units of phospholipase C/ml), phospholipase C increased prostaglandin E2 formation to the level observed with phospholipase A2. Phospholipase A2 enhanced the release only of unsaturated fatty acids, whereas phospholipase C stimulated the release of individual free fatty acids (C 16:0, C 18:0, C 18:1, C 18:2 and C 20:4). Moreover, p-bromophenacyl bromide inhibited phospholipase A2-stimulated prostaglandin E2 production and the release of fatty acids, but it had no influence on prostaglandin E2 formation and the release of fatty acids increased by phospholipase C, indicating that the stimulatory effect of phospholipase C is not mediated through the activation of endogenous phospholipase A2. These results suggest the presence of diacylglycerol lipase and monoacylglycerol lipase in the kidney and the importance of this pathway in prostaglandin synthesis by the kidney.