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PloS One 2012This study analyzed the effect of in utero exposure to maternal diabetes on contraction to noradrenaline in mesenteric resistance arteries (MRA) from adult offspring,...
This study analyzed the effect of in utero exposure to maternal diabetes on contraction to noradrenaline in mesenteric resistance arteries (MRA) from adult offspring, focusing on the role of cyclooxygenase (COX)-derived prostanoids. Diabetes in the maternal rat was induced by a single injection of streptozotocin (50 mg/kg body weight) on day 7 of pregnancy. Contraction to noradrenaline was analyzed in isolated MRA from offspring of diabetic (O-DR) and non-diabetic (O-CR) rats at 3, 6 and 12 months of age. Release of thromboxane A(2) (TxA(2)) and prostaglandins E(2) (PGE(2)) and F(2α) (PGF(2α)), was measured by specific enzyme immunoassay kits. O-DR developed hypertension from 6 months of age compared with O-CR. Arteries from O-DR were hyperactive to noradrenaline only at 6 and 12 months of age. Endothelial removal abolished this hyperreactivity to noradrenaline between O-CR and O-DR. Preincubation with either the COX-1/2 (indomethacin) or COX-2 inhibitor (NS-398) decreased noradrenaline contraction only in 6- and 12-month-old O-DR, while it remained unmodified by COX-1 inhibitor SC-560. In vessels from 6-month-old O-DR, a similar reduction in the contraction to noradrenaline produced by NS-398 was observed when TP and EP receptors were blocked (SQ29548+AH6809). In 12-month-old O-DR, this effect was only achieved when TP, EP and FP were blocked (SQ29548+AH6809+AL8810). Noradrenaline-stimulated TxB(2) and PGE(2) release was higher in 6- and 12-month-old O-DR, whereas PGF(2α) was increased only in 12-month-old O-DR. Our results demonstrated that in utero exposure to maternal hyperglycaemia in rats increases the participation of COX-2-derived prostanoids on contraction to noradrenaline, which might help to explain the greater response to this agonist in MRA from 6- and 12-month-old offspring. As increased contractile response in resistance vessels may contribute to hypertension, our results suggest a role for these COX-2-derived prostanoids in elevating vascular resistance and blood pressure in offspring of diabetic rats.
Topics: Animals; Cells, Cultured; Cyclooxygenase 2; Diabetes Mellitus, Experimental; Dinoprost; Endothelial Cells; Female; Immunoenzyme Techniques; Indomethacin; Male; Mesenteric Arteries; Nitrobenzenes; Norepinephrine; Pregnancy; Prostaglandins; Prostaglandins E; Prostaglandins F; Rats; Sulfonamides; Thromboxane A2; Xanthones
PubMed: 23209788
DOI: 10.1371/journal.pone.0050593 -
Fertility and Sterility Jul 1975The current study was formulated to investigate the abortifacient activity of prostaglandin 15-methyl F2alpha (15-methyl PGF2alpha) administered intramuscularly to 80... (Comparative Study)
Comparative Study
The current study was formulated to investigate the abortifacient activity of prostaglandin 15-methyl F2alpha (15-methyl PGF2alpha) administered intramuscularly to 80 healthy women with gestations between 8 and 22 weeks. Goals were the establishment of an effective dosage schedule and assessment of the incidence and severity of side effects. All 80 gravidas were aborted, with a mean time to abortion of 15.70 hours (SD, 6.52). Gastrointestinal side effects occurred in 89% of the patients; temperature elevations greater than or equal to 100.6 degrees F were noted in 14 cases. No other significant complications were encountered. Transabdominal intra-amniotic pressure monitoring indicated the need to administer the drug at 2-hour intervals. The 15-methyl PGF2alpha patients were matched for parity and gestational length with 80 gravidas aborted with PGE2 20-mg vaginal suppositories. The difference in interval to abortion in the two groups was not statistically significant. While gastrointestinal side effects were more common with 15-methyl PGF2alpha, the frequency of drug-induced temperature elevations was reduced.
Topics: Abortion, Induced; Adolescent; Adult; Diarrhea; Female; Humans; Injections, Intramuscular; Oxytocin; Pregnancy; Pregnancy Trimester, First; Pregnancy Trimester, Second; Prostaglandins E; Prostaglandins F; Suppositories; Vacuum Curettage; Vomiting
PubMed: 1149900
DOI: No ID Found -
Fertility and Sterility Nov 1985As a model to examine the pathophysiologic attributes of endometriosis, attempts were made to surgically induce the disease in the rat by autotransplanting endometrial...
As a model to examine the pathophysiologic attributes of endometriosis, attempts were made to surgically induce the disease in the rat by autotransplanting endometrial or uterine tissue to the peritoneum. Rats (n = 46) were randomly assigned to one of four surgical techniques: (1) four uterine squares sutured to the peritoneal cavity; (2) uterine luminal lavages instilled into the peritoneal cavity; (3) endometrial scrapings flushed into the peritoneal cavity; and (4) sham-operated controls. Rats were examined at various days after surgery for the presence of endometrial implants. The autotransplantation of uterine squares to the peritoneal cavity was the only treatment that yielded healthy endometriotic implants. These implants grew into ellipsoidal cystic structures that were composed of both endometrial glands and stroma and were found to contain prostaglandin F (202 ng/mg) at concentrations similar to those measured in uterine tissue (205 ng/mg). To examine the effect of surgically induced endometriosis upon fecundity, rats (n = 40) were autotransplanted with uterine squares or were sham operated and mated. The presence of ectopic endometrial tissue reduced the number of pups at term by 48% and the number of day 14 embryos by 28% (P less than 0.05). Peritoneal adhesions were greater in rats with induced endometriosis than in sham-operated controls (P less than 0.05); however, in rats with induced endometriosis, no differences were noted in the severity of adhesions between pregnant and nonpregnant rats. Endometriotic implants underwent complete regression in the day 14 pregnant rat but had doubled in size in the nonpregnant rat. At term, the endometriotic implants were larger than in the day 14 pregnant rat (P less than 0.05) and similar to their original size. The successful growth and development of surgically transplanted endometrial tissue in the rat offers a research model that can be used to study those aspects of endometriosis that cannot be adequately investigated in women.
Topics: Analysis of Variance; Animals; Endometriosis; Endometrium; Female; Litter Size; Pregnancy; Prostaglandins F; Radioimmunoassay; Rats; Rats, Inbred Strains; Transplantation, Autologous; Uterus
PubMed: 4054348
DOI: No ID Found -
BMC Ophthalmology Mar 2016Differences in the increase in matrix metalloproteinase (MMP) and decrease in tissue inhibitor of metalloproteinase (TIMP) activity may contribute to the different...
BACKGROUND
Differences in the increase in matrix metalloproteinase (MMP) and decrease in tissue inhibitor of metalloproteinase (TIMP) activity may contribute to the different characteristics observed clinically on decreased intraocular pressure in patients with glaucoma or ocular hypertension. The purpose of this study was to investigate differences in the expression profiles of MMPs and TIMPs induced by the prostaglandin analogs bimatoprost, latanoprost, and tafluprost in human non-pigmented ciliary epithelial cells (HNPCECs).
METHODS
HNPCECs were cultured for 24 h with 0, 10, 100, or 1000 μM of the free acid forms of bimatoprost, latanoprost, and tafluprost. We measured the expression levels of MMPs and TIMPs using real-time polymerase chain reaction, and compared the results. Enzyme activities of MMP-2 and -9 in conditioned media were measured by gelatin zymography.
RESULTS
All prostaglandin analogs we examined dose-dependently increased expression levels of MMP-1, -2, -3, -9, and -17, whereas expression levels of TIMP-1 and -2 decreased with increasing concentrations of each analog. Each prostaglandin analog induced different levels of increases in MMPs and decreases in TIMPs.
CONCLUSIONS
Unique expression profiles of MMPs and TIMPs induced by bimatoprost, latanoprost, and tafluprost, as shown in HNPCECs, may contribute to clinically different effects on intraocular pressure decreases in patients with glaucoma or ocular hypertension.
Topics: Antihypertensive Agents; Bimatoprost; Cell Line; Ciliary Body; Dose-Response Relationship, Drug; Epithelial Cells; Gene Expression Regulation, Enzymologic; Humans; Latanoprost; Matrix Metalloproteinases; Prostaglandins F; Prostaglandins F, Synthetic; RNA, Messenger; Real-Time Polymerase Chain Reaction; Tissue Inhibitor of Metalloproteinases
PubMed: 26956170
DOI: 10.1186/s12886-016-0202-8 -
Kidney International Jun 1981
Review
Topics: Animals; Dinoprost; Epoprostenol; Guinea Pigs; Haplorhini; Hydroxyprostaglandin Dehydrogenases; Kidney; Kidney Cortex; Kidney Medulla; Microsomes; Prostaglandin-Endoperoxide Synthases; Prostaglandins; Prostaglandins E; Prostaglandins F; Rabbits; Rats; Swine
PubMed: 6790807
DOI: 10.1038/ki.1981.78 -
British Journal of Cancer Sep 1987Prostaglandins E2 and F2 alpha (PGE2 and PGF2 alpha) were measured by gas liquid chromatography--mass spectrometry (glc-ms) in extracts of primary tumours from 78...
Prostaglandins E2 and F2 alpha (PGE2 and PGF2 alpha) were measured by gas liquid chromatography--mass spectrometry (glc-ms) in extracts of primary tumours from 78 patients with early breast cancer. These levels have been related to factors of established prognostic value and the patients disease-free interval. Although there was a wide variation in amounts of both prostaglandins extracted from different tumours, no significant relationship was observed between levels of prostaglandins and oestrogen receptors (ER), tumour size, presence of lymph node involvement and disease-free interval following primary treatment. It therefore seems unlikely that the level of these particular prostaglandins within breast carcinomas plays a fundamental role in the prognosis of the disease.
Topics: Breast Neoplasms; Dinoprost; Female; Humans; Neoplasm Staging; Prognosis; Prostaglandins; Prostaglandins E; Prostaglandins F; Receptors, Estrogen
PubMed: 3478073
DOI: 10.1038/bjc.1987.204 -
Journal of Dairy Science Aug 2010Two experiments evaluated the influence of follicular wave at artificial insemination (AI) on fertility of dairy cows. In experiment 1, data from 5,607 lactating cows...
Two experiments evaluated the influence of follicular wave at artificial insemination (AI) on fertility of dairy cows. In experiment 1, data from 5,607 lactating cows enrolled in estrous and ovulation synchronization programs for AI were evaluated. Cows' blood was analyzed for progesterone 7 to 14 d apart, with the second sample collected on the day of the first GnRH (GnRH1) of the synchronization protocol. Cows were classified as cyclic if progesterone was >or=1 ng/mL in at least 1 of the 2 samples and as anovular if both samples were <1 ng/mL. Cyclic cows were categorized as low (CLOW;<1 ng/mL) or high (CHIGH; >or= 1 ng/mL) progesterone on the day of GnRH1, which would result in ovulation of the dominant follicle of the first (FW) and second (SW) follicular waves, respectively, at AI. Pregnancy per AI (P/AI) was determined 30 and 53 d after AI. In experiment 2, 220 cyclic Holstein cows received 2 injections of PGF(2alpha) administered 14 d apart. The Ovsynch protocol (d 0 GnRH, d 7 PGF(2alpha), d 9 GnRH, d 9.5 timed AI) was initiated either 3 or 10 d after the second PGF(2alpha) of the presynchronization to result in insemination to the FW or SW dominant follicles. Blood was analyzed for progesterone and ovaries were scanned to determine ovulatory responses and follicle diameter. Pregnancy was determined on d 32 and 67 after timed AI. In experiment 1, P/AI on d 30 was greater for CHIGH cows than for CLOW and anovular cows (43.0, 31.3, and 29.7%, respectively), but because of pregnancy loss, P/AI on d 53 was lowest for anovular cows. Proportions of cows with short reinsemination intervals differed among groups and were 7.1, 15.7, and 11.9% for CHIGH, CLOW, and anovular cows, respectively. Pregnancy loss was greater for anovular cows than for CLOW cows (15.0 vs. 10.0%) and was intermediate for CHIGH cows (13.5%). In experiment 2, 9.8 and 97.2% of the FW and SW cows, respectively, had progesterone >or=1 ng/mL at GnRH1. Concentrations of progesterone at the GnRH1 and PGF(2alpha) injections of the Ovsynch protocol were greater for SW cows than FW cows. Pregnancy per AI was greater for SW cows than for FW cows (41.7 vs. 30.4%) despite less ovulation to GnRH1 in SW cows than in FW cows (78.7 vs. 88.4%). Collectively, these data indicate that follicular wave of the ovulatory follicle and not cyclic status caused the greatest reduction in P/AI in dairy cows. Whether the culprit is the follicle itself or the hormonal milieu characteristic of the first follicular wave and the early stage of the estrous cycle remains to be elucidated. Synchronization programs that induced ovulation of the FW follicle at AI reduced P/AI in lactating dairy cows, and ovulation of the FW follicle, or development of the ovulatory follicle under low progesterone concentrations, or both, might be mechanisms for reduced fertility in anovular cows.
Topics: Animals; Anovulation; Cattle; Cattle Diseases; Estrus Synchronization; Female; Fertility; Fertility Agents, Female; Gonadotropin-Releasing Hormone; Insemination, Artificial; Lactation; Ovarian Follicle; Ovulation; Pregnancy; Progesterone; Prostaglandins F
PubMed: 20655426
DOI: 10.3168/jds.2010-3047 -
The Journal of Physiology Jul 19811. The effect of i.v. administration of prostaglandin (PG) E(2) (10-40 mug kg(-1) h(-1)), 16,16-dimethyl PGE(2) (0.1-0.5 mug kg(-1) h(-1)), PGE(1) (16-20 mug kg(-1)...
1. The effect of i.v. administration of prostaglandin (PG) E(2) (10-40 mug kg(-1) h(-1)), 16,16-dimethyl PGE(2) (0.1-0.5 mug kg(-1) h(-1)), PGE(1) (16-20 mug kg(-1) h(-1)), PGA(1) (5-11 mug kg(-1) h(-1)) and PGF(2alpha) (40 mug kg(-1) h(-1)) on the relationship between [H(+)] and flow of gastric juice during stimulation of gastric secretion by pentagastrin was investigated in conscious cats prepared with cannulated gastric fistulae.2. A- and E-type prostaglandins significantly reduced pentagastrin-stimulated acid output. This inhibition was associated with a reduction of the [H(+)] of the gastric juice such that the [H(+)] observed at any flow rate tended to be lower than the normal range observed with pentagastrin alone. With the highest doses of these prostaglandins the mean [H(+)] values were well below the normal range with pentagastrin alone.3. At the dose tested, PGF(2alpha) had little effect on acid output, and did not alter the relationship between [H(+)] and gastric flow.4. There is a linear relationship between acid output and gastric flow and this relationship is similar during stimulation of gastric secretion by pentagastrin, histamine or insulin. Gastric acid inhibitory doses of cimetidine, atropine and somatostatin did not alter this relationship. In contrast the A- and E-type prostaglandins displaced this relationship to the right of the normal line observed with the acid stimulants alone. A- and E-type prostaglandins reduced the slope of the line relating acid output and gastric flow from approximately 150-170 muequiv/ml(-1) to approximately 100-120 muequiv ml(-1), this being taken as evidence of dilution of the parietal H(+) secretion with a non-parietal secretion.5. The volume of non-parietal gastric secretion was calculated as the gastric flow at zero acid output by extrapolation of linear plots of acid output versus gastric flow. Unstimulated gastric flow measured directly was 0.75 ml 15 min(-1). The calculated non-parietal flow was in the range 0.52-0.90 ml 15 min(-1) during stimulation of gastric secretion with pentagastrin, histamine and insulin, and inhibition of pentagastrin-stimulated acid secretion with cimetidine, atropine and somatostatin. PGE(2) (1.51 ml 15 min(-1)) and 16,16-dimethyl PGE(2) (1.20 ml 15 min(-1)) nearly doubled the calculated non-parietal flow.6. These data demonstrate that gastric acid inhibitory doses of A- and E-type prostaglandins can reduce the [H(+)] in the bulk fluid of the gastric lumen during stimulation of acid secretion. The data provide evidence that these prostaglandins stimulate a non-parietal component of gastric secretion. This might be gastric bicarbonate and mucus secretion.
Topics: Alprostadil; Animals; Cats; Dinoprost; Dinoprostone; Gastric Acid; Gastric Juice; Hydrogen-Ion Concentration; Pentagastrin; Prostaglandins; Prostaglandins A; Prostaglandins E; Prostaglandins F; Secretory Rate
PubMed: 6948108
DOI: 10.1113/jphysiol.1981.sp013798 -
British Journal of Pharmacology Dec 1986TRK-100, a stable analogue of prostaglandin I2 (PGI2), relaxed isolated arteries of the dog precontracted with PGF2 alpha or K+; the relaxation was in the order of...
TRK-100, a stable analogue of prostaglandin I2 (PGI2), relaxed isolated arteries of the dog precontracted with PGF2 alpha or K+; the relaxation was in the order of mesenteric and renal greater than coronary and femoral greater than basilar and middle cerebral arteries. The relaxation by TRK-100 was not affected by treatment with atropine, propranolol, cimetidine, aminophylline, and indomethacin, but was suppressed by diphloretin phosphate, a prostaglandin antagonist. Treatment with TRK-100 attenuated the contraction induced by PGF2 alpha and Ca2+ in mesenteric and basilar arteries previously exposed to Ca2+-free medium, but did not significantly alter the contractile response to Ca2+ in the arteries exposed to Ca2+-free medium and depolarized by excess K+. TRK-100 and nitroglycerin relaxed isolated mesenteric arteries to a similar extent; however, when continuously infused into mesenteric arteries in anaesthetized dogs, TRK-100 produced greater vasodilatation than nitroglycerin. It is concluded that TRK-100 relaxes dog mesenteric and renal arteries more than cerebral arteries; the relaxation appears to derive from interference with the release of Ca2+ from intracellular stores and with the transmembrane Ca2+ influx through a receptor-operated channel. TRK-100 may vasodilate large and small mesenteric arteries and resistance vessels to a similar extent, whereas nitroglycerin preferentially dilates the large artery.
Topics: Animals; Basilar Artery; Calcium; Dinoprost; Dogs; Epoprostenol; Female; In Vitro Techniques; Male; Muscle Contraction; Muscle, Smooth, Vascular; Nitroglycerin; Polyphloretin Phosphate; Prostaglandins F; Splanchnic Circulation; Vasodilator Agents
PubMed: 3101928
DOI: 10.1111/j.1476-5381.1986.tb11174.x -
Environmental Health Perspectives Apr 1986New Zealand White rabbits were acutely bronchochallenged for 5 min to ascertain airway responsiveness with six potential byssinogenic agents and mediators: 0.1 g/mL... (Review)
Review
New Zealand White rabbits were acutely bronchochallenged for 5 min to ascertain airway responsiveness with six potential byssinogenic agents and mediators: 0.1 g/mL cotton dust extract (CDE), 0.1 g/mL cotton bract extract (CBE), 1 mg/mL endotoxin, 1 mg/mL n-formyl methionyl peptide (n-fMet), 10 mg/mL 5-hydroxytryptamine (5-HT), and 1 mg/mL prostaglandin F2 alpha (PGF2 alpha). Methacholine (MC), 10 mg/mL, was used as a control bronchoconstrictor. Clinically objective criteria were established using increases in resistance values compared to those obtained with saline controls. Animals were classified as: mild responders (Mi) = 125-149%; moderate responders (Mo) = 150-199%; or severe responders (S) = greater than 200%. Three of five (2Mo, 1S) rabbits showed increased pulmonary resistance to CDE bronchochallenge, 3/5 (1Mi, 1Mo, 1S) to CBE, 1/5 (Mo) to purified endotoxin, 4/5 (1Mo, 3S) to n-fMet, 3/5 (1Mi, 1Mo, 1S) to 5-HT, and 2/5 (1Mo, 1S) to PGF2 alpha. All five rabbits (1Mo, 4S) responded to MC bronchochallenge. Rabbits responded minimally to saline, the common solvent of all test agents; however, when challenged with methacholine, a known bronchoconstrictor, rabbits showed significant overt symptoms of acute respiratory distress with immediate and substantial increases in resistance over saline controls. CDE, CBE, and n-fMet inhalation challenge resulted in a majority or all animals showing increased resistance. 5-HT contained in CDE and CBE, exhibited similar resistance increases; however, endotoxin, also found in cotton dust, showed little airway reactivity. The rabbit is useful for characterizing changes in pulmonary function parameters seen in the acute byssinotic reaction. This study has demonstrated that bronchochallenge in the rabbit with potential byssinogenic agents (CDE, CBE, endotoxin, and n-fMet) and mediators (5-HT and PGF2 alpha) result in measurable changes in airway function, particularly increased resistance. Since bronchoconstriction is the major clinical manifestation of the acute byssinotic reaction in man and animals, it is likely that bronchoconstriction observed in cotton mill workers may be in part or totally the result of inherent dust constrictor substances or secondarily released mediators.
Topics: Airway Resistance; Animals; Bronchial Provocation Tests; Byssinosis; Dinoprost; Dust; Endotoxins; Female; Gossypium; N-Formylmethionine; Prostaglandins F; Rabbits; Respiratory Function Tests; Serotonin
PubMed: 3519204
DOI: 10.1289/ehp.866661