The effect of prostaglandins E2 and F2 alpha on carotid blood flow in rats with renovascular hypertension

The effect of i.v. bolus administration of PGE2 and PGF2 alpha on carotid blood flow (Q) and mean arterial blood pressure (MAP) was recorded in 21 anaesthetized normotensive control (N) and 12 rats with 1K1C renovascular hypertension (RH). From the measured parameters the regional vascular impedance (PVI) and the change in blood volume were calculated. In normotensive animals both PGs elicited a dose-dependent initial fast increase of Q (threshold dose 0.4 ng/kg) and a decrease of MAP and PVI (threshold dose 0.4 micrograms/kg). Subsequently, Q decreased below the initial level. MAP and PVI remained depressed after E2 but increased after F2 alpha. The time course of the Q and MAP responses was analyzed in more detail at a standard dose 4 micrograms/kg. The average time to peak of the first phase was 12 s and of the second approximately 80 s. The initial levels of Q and MAP were reestablished within 3 to 4 minutes. The total volume of carotid blood flow obtained by planimetric integration was unaltered after F2 alpha but depressed after E2. In hypertensive animals both phases of the response to E2 were significantly retarded and the Q response was nearly abolished. On the other hand, the time course of the reaction to F2 alpha was unchanged but the magnitude of the second pressoric phase was reduced. Thus, the capacity of the carotid vascular bed to dilate remains the same in RH while the ability to constrict is limited. It is concluded that the response of MAP and Q to both PGs are relatively independent.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of prostaglandins E1, E2 and F2alpha on neutrophil aggregation.

Recently we have found that chemotactic factors stimulate neutrophils in suspension to aggregate. Because of an obvious analogy to platelet aggregation, we examined the influence of three prostaglandins on this process. Prostaglandins E1, E2 and F2alpha alone did not cause aggregation of the neutrophils but were able to partially inhibit the aggregation response induced by the synthetic chemotactic tripeptide, formyl-methionyl-leucyl-phenylalanine. The minimal inhibitory concentrations for prostaglandins E1, E2 and F2alpha were 10(-7), 10(-6) and 10(-5)M, respectively. These results are similar to those found for the prostaglandin-induced inhibition of platelet aggregation. It may be, therefore, that neutrophil aggregation, like platelet aggregation, is modulated by intracellular prostaglandins and other products of arachidonic acid metabolism.     

Effect of prostaglandins E2 and F2α on umbilical blood flow and fetal hemodynamics

The hemodynamic effects of PGF_2α, PGE₂, and norepinephrine injected into the umbilical arterial circulation were compared in nine fetal lambs in utero. Umbilical blood flow was measured with radioactive microspheres and an electromagnetic flow transducer implanted on the distal aorta of the fetus after ligation of external iliac arteries and other accessible distal aortic branches.PGF_2α and norepinephrine increased fetal arterial pressure and umbilical blood flow while umbilical vascular resistance increased slightly (PGF_2α) or not at all (norepinephrine). PGE₂ increased fetal arterial pressure, decreased umbilical blood flow, and exerted a profound active vasoconstrictor effect on the fetal placental bed. Our data taken together with the observations of others suggest that prostaglandins may play a role in the circulatory adaptations of the fetus at birth and that PGE₂ in high concentrations is likely to have deleterious hemodynamic consequences in the fetus in utero.     

Effect of prostaglandins E1 and F2 alpha on neuromuscular transmission in the frog sartorius muscle.

End plate potentials (e.p.p.s.) and miniature end plate potentials (m.e.p.p.s.) were recorded intracellularly at the neuromuscular junction of the frog sartorius muscle. Addition of as little as 8.5 x10(-8)M PGE1 reduced the mean m.e.p.p. frequency. The mean amplitude of m.e.p.p.s was not changed, the mean amplitude of the e.p.p.s and the quantum content of the transmitter released by a nerve impulse was slightly reduced. A decrease in mean m.e.p.p. frequency was also seen in response to the administration of 8.5 x 10(-8)M PG2 alpha. The mean amplitude of e.p.p.s and m.e.p.p.s and the quantum content remained unchanged. The possible presynaptic mode of action of PGs in the preparation of discussed.     

E and F alpha series prostaglandins in developing muscles

Prostaglandins are known to affect myoblast proliferation and fusion in vitro and are putative regulators of in vivo myogenesis. The levels of E and F alpha series prostaglandins in the thigh muscles of chicken embryos were measured by radioimmunoassays and correlated with indicators of muscle development. Just prior to the onset of secondary myogenesis, the amounts of PGE1, PGE2 and PGF1 alpha plus PGF2 alpha per mg of protein were high. In temporal association with myotube formation, the amount of PGE1 and PGE2 per mg of protein decreased. PGF alpha levels also fell, but at a slower rate than observed with the E series prostaglandins. The decreases in the amounts of prostaglandins per mg protein appeared to be due to a decline in the total amount of prostaglandin within each muscle. These observations are consistent with prostaglandins being one of the factors that controls in vivo muscle formation.     

Immunohistochemical localization of prostaglandins E and F2 alpha in the developing murine palate

Prostaglandins E2 and F2 alpha (PGE2 and PGF2 alpha) have been shown to cause changes in adenosine 3',5'-cyclic monophosphate (cAMP) levels in a wide variety of tissues. In particular, murine palatal mesenchyme responds to PGE2 stimulation with dose-dependent increases in intracellular cAMP levels. These same mesenchymal cells also synthesize PGE2 and PGF2 alpha. The purpose of this study is to localize PGE and PGF2 alpha in the developing murine palate by using immunohistochemical techniques. Fresh frozen cryostat sections of murine C57BL/6J embryo palates (days 12-14 of gestation) were incubated with anti-PGE or PGF2 alpha monoclonal antibodies. On day 12 of gestation, PGE and PGF2 alpha, identified as 3',3-diaminobenzidine (DAB) reaction products, were localized throughout palatal mesenchyme and epithelium; on day 13 of gestation, reaction product indicative of both PGE and PGF2 alpha was detectable primarily in mesenchyme subjacent to palatal epithelium. Extracellular spaces of the adjacent mesenchyme in the central region of the day 13 palate exhibited less reaction product. Palatal epithelium, particularly the medial edge epithelium, exhibited a diminished amount of reaction product for both prostaglandins on day 13 as compared to the underlying mesenchyme. After formation of a midline epithelial seam between homologous palatal processes on day 14 of gestation, medial edge, oral, and nasal epithelium exhibited light staining for PGE or PGF2 alpha. Palate mesenchymal cells subjacent to the midline seam exhibited a diminished amount of reaction product for both PGE and PGF2 alpha as compared to day 13 of gestation. Overall, the results show local and temporal changes in the distribution of prostaglandins in the developing murine palate.     

The central nervous effect of prostaglandins I2, E2 and F2 alpha on aconitine-induced cardiac arrhythmia in rats.

Intracerebroventricular administration of PGI2 or PGE2 reduced aconitine-induced cardiac arrhythmia in rats. PGF2 alpha had no antiarrhythmic effect under the same conditions. The ED50 values of PGI2 and E2 were 0.25 microgram/kg and 1.1 microgram/kg, respectively. Central mechanisms may participate in the antiarrhythmic effect of these PGs.     

Metabolism of prostaglandins E2 and F2 alpha by human fetal membranes.

Prostaglandin E2 (PGE2) is important in the early stages of human labour, leading particularly to cervical ripening and dilatation. The source of PGE2 is thought to be either the amnion or the decidua, but the chorion interposes between the amnion and the target tissues, namely the myometrium and cervix. In order to investigate the role of the chorion in modulating prostanoid production, [3H]PGE2 was added to the amnion side of fetal membranes, and the production of metabolites on both sides of the fetal membrane followed by HPLC. The major metabolite was 13,14-dihydro-15-oxo-PGE2 with smaller amounts of 13,14-dihydro-15-oxo-PGA2 and PGB2. The production of all metabolites of PGE2 was time dependent. [3H]PGF2 alpha, which is normally produced by the decidua, was also added to fetal membranes and found to be metabolised to 13,14-dihydro-15-oxo-PGF2 alpha and PGE2. These results suggest that the metabolic enzymes in the chorion may determine intra-uterine levels of prostaglandins, and may also determine the identity of the eicosanoids released by intact fetal membranes.     

Effects of intracerebroventricular administration of prostaglandins I2, E2, F2 alpha and indomethacin on blood pressure in the rat.

The effects of intraventricularly administered prostaglandins I2 (PGI2), E2 (PGE2), F2alpha (PGF2 alpha) and indomethacin on systemic blood pressure were investigated in conscious rats. PGI2 (1.25--10 micrograms/kg) decreased blood pressure in a dose-related manner, whereas PGE2 (100--1000 mg/kg) dose-dependently increased blood pressure. Both PGF2 alpha (0.31--20 micrograms/kg) and indomethacin (0.625--40 micrograms/kg) had no effects on blood pressure. These results indicate that intraventricular injection of PGI2 or PGE2 can induce significant changes in blood pressure, while endogenous prostaglandins synthesized in the brain seem to play a minor role in direct regulation of systemic blood pressure in the rat.