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The Yale Journal of Biology and Medicine 1986Prostaglandin (PG) E2 is a potent hyperthermic agent and has been assigned an intermediary function in the response of thermoregulatory neurons to pyrogens. Though...
Prostaglandin (PG) E2 is a potent hyperthermic agent and has been assigned an intermediary function in the response of thermoregulatory neurons to pyrogens. Though attractive, this idea has been challenged on several grounds. The present study confirms that brain PGE2 synthesis increases during fever, the time course of the elevation according with a causative role of the compound. Our experimental data also argue against the involvement of a second cyclooxygenase product, specifically thromboxane (TX) A2, in the action of pyrogens. The sequence of events leading to PGE2 production and fever differs depending on the pyrogen, bacterial vs. leucocytic, and its route of administration. Blood-borne interleukin-1 (IL-1) acts on a discrete site in the central nervous system (CNS) which is tentatively identified with the organum vasculosum laminae terminalis (OVLT). The same site may also be the target for blood-borne endotoxin. In addition, endotoxin may promote PGE2 synthesis in the cerebral microvasculature. Both pyrogens, on the other hand, act diffusely throughout the CNS when given intrathecally. We conclude that PGE2 is well suited for an intermediary role in the genesis of fever and ascribe the reported inconsistencies to methodological factors.
Topics: Animals; Cerebrovascular Circulation; Dinoprostone; Fever; Humans; Hypothalamus; Interleukin-1; Prostaglandins E; Pyrogens; Thromboxane A2
PubMed: 3488620
DOI: No ID Found -
British Medical Journal Sep 1976
Topics: Abortion, Induced; Female; Humans; Pregnancy; Pregnancy Trimester, Second; Prostaglandins E; Urea
PubMed: 963450
DOI: 10.1136/bmj.2.6035.587-a -
Japanese Journal of Pharmacology Nov 1985In order to evaluate the participation of prostaglandins and bradykinin in autoregulation of renal blood flow, the pressure-flow relationships were examined before and...
In order to evaluate the participation of prostaglandins and bradykinin in autoregulation of renal blood flow, the pressure-flow relationships were examined before and during the infusion of prostaglandin E2, sodium arachidonate or bradykinin in the pump-perfused kidney of anesthetized dogs. Renal arterial pressure was changed in a step-wise fashion between 60 and 200 mmHg by means of a pneumatic resistance. Renal blood flow revealed an effective autoregulation against the pressure changes between 100 and 200 mmHg. Infusion of prostaglandin E2 (30 and 100 ng/min), sodium arachidonate (200 and 500 micrograms/min) or bradykinin (100 and 300 ng/min) into the renal artery increased renal blood flow dose-dependently, but had no influence on the autoregulation of renal blood flow. We also examined the effect of endogenous bradykinin and prostaglandins by the intravenous administration of captopril (1 mg/kg), a kininase II inhibitor, and indomethacin (2.5 mg/kg), a cyclo-oxygenase inhibitor, respectively. Captopril increased renal blood flow, but did not impair the autoregulation. Indomethacin decreased renal blood flow and had no effect on the renal autoregulation. It is considered that prostaglandins and bradykinin which induced renal vasodilation have no role in the autoregulation of renal blood flow in the dog kidney.
Topics: Animals; Arachidonic Acid; Arachidonic Acids; Blood Pressure; Bradykinin; Captopril; Dinoprostone; Dogs; Female; Homeostasis; Indomethacin; Kidney; Male; Prostaglandins; Prostaglandins E; Renal Circulation
PubMed: 3937925
DOI: 10.1254/jjp.39.349 -
The Journal of Investigative Dermatology May 1991
Topics: Eicosanoids; Humans; Prostaglandins E; Skin
PubMed: 2022887
DOI: 10.1111/1523-1747.ep12471793 -
Annals of the Rheumatic Diseases Aug 1981Twelve patients with systemic sclerosis (SS) and severe Raynaud's phenomenon received infusions of prostaglandin E1 (PGE1) at a dose of 6-10 ng/kg/min, with either... (Clinical Trial)
Clinical Trial
Twelve patients with systemic sclerosis (SS) and severe Raynaud's phenomenon received infusions of prostaglandin E1 (PGE1) at a dose of 6-10 ng/kg/min, with either saline or 5% dextrose, for 72 hours in a single-blind cross-over study. The infusions were administered intravenously by centrally positioned catheters. Infusions were well tolerated with only mild side effects. Following the PGE1 infusion cold tolerance improved and attacks of Raynaud's phenomenon were less frequent, less severe, and shorter in duration. This subjective improvement was maintained for several weeks in most patients, and 2 noted healing of ischaemic ulcers. There was no significant change in objective measurements of hand function after either infusion. However, pain measured on a 10 cm visual analogue scale improved 2.19 cm with PGE1 and only 0.91 cm with normal saline (P less than 0.05). Temperature of the fingers and hands recorded by thermography did not change significantly with saline infusions, but did rise during PGE1 infusions (mean rise 2.0 degrees C at 48 hours, p less than 0.001), and was maintained when measured again 2 weeks later (mean rise 1.56 degrees C, p less 0.001). PGE1 may therefore be suitable treatment for Raynaud's phenomenon and the vascular insufficiency of systemic sclerosis and other connective tissue diseases.
Topics: Adult; Aged; Female; Hand; Humans; Infusions, Parenteral; Male; Middle Aged; Prostaglandins E; Raynaud Disease; Scleroderma, Systemic; Thermography
PubMed: 7259326
DOI: 10.1136/ard.40.4.350 -
The British Journal of Ophthalmology Apr 1987The plasma lipid alterations characteristic of essential fatty acid deficiency (EFAD) generally appear one to two weeks after the initiation of fat free parenteral...
The plasma lipid alterations characteristic of essential fatty acid deficiency (EFAD) generally appear one to two weeks after the initiation of fat free parenteral nutritional (PN), and may be associated with a reduction in prostaglandin (PG) formation. In the present study the relationship between exclusion of fat from the diet and changes in intraocular pressure (IOP) and PGE2 plasma levels were studied in 28 patients. The results indicated that three weeks after the omission of dietary fat a significant reduction in IOP levels occurred which persisted throughout the follow-up period of 7 (SD 1.2) weeks. Plasma PGE2 levels were also significantly reduced in patients on fat free PN for three weeks as compared with levels measured while patients were on a fat containing diet. This clinical observation is not yet understood and might be related to changes exerted by fatty acid deficiency.
Topics: Adult; Dietary Fats; Dinoprostone; Fatty Acids, Essential; Female; Humans; Intraocular Pressure; Male; Middle Aged; Parenteral Nutrition; Prostaglandins E; Prostaglandins E, Synthetic
PubMed: 3107613
DOI: 10.1136/bjo.71.4.254 -
The Tohoku Journal of Experimental... Apr 1978To determine the effect of aldosterone antagonist on renal prostaglandin E synthesis, the rate of urinary excretion of immunoreactive prostaglandin E was measured...
To determine the effect of aldosterone antagonist on renal prostaglandin E synthesis, the rate of urinary excretion of immunoreactive prostaglandin E was measured radioimmunologically before and during the oral administration of an aldosterone antagonist, spironolactone, in 5 patients with essential hypertension, 3 with primary aldosteronism and 2 with postoperative primary aldosteronism. Spironolactone was administered at an oral dose of 25 mg 4 times daily for about 1 week. In the control state, the rates of urinary prostaglandin E excretion ranged from 151 ng/day to 4,527 ng/day in essential hypertension. The rates were not augmented in primary aldosteronism but decreased after the removal of an aldosterone producing adenoma. No obvious relationship was observed between plasma aldosterone concentration and the rate of urinary prostaglandin E excretion. On the first day of spironolactone administration, the excretion rates of urinary prostaglandin E were markedly increased independently of basal plasma aldosterone level in all cases except one case of essential hypertension. Urinary prostaglandin E excretion was increased with the concominant increase of urinary Na/K ratio in essential hypertension and primary aldosteronism. After the second day, the augmented urinary prostaglandin E excretion was decreased and the changes of urinary prostaglandin E excretion varied from case to case. These results suggest that synthesis of renal prostaglandin E is not mainly regulated by aldosterone in essential hypertension and primary aldosteronism.
Topics: Adult; Female; Humans; Hyperaldosteronism; Hypertension; Kallikreins; Kidney; Kinins; Male; Middle Aged; Prostaglandins E; Spironolactone
PubMed: 663929
DOI: 10.1620/tjem.124.297 -
British Journal of Pharmacology Mar 19791. Plasma exudation and blood flow changes induced by intradermal injection of prostaglandins E2 (PGE2), I2 (PG12), D2 (PGD2) and F2 alpha (PGF2 alpha) were measured in...
1. Plasma exudation and blood flow changes induced by intradermal injection of prostaglandins E2 (PGE2), I2 (PG12), D2 (PGD2) and F2 alpha (PGF2 alpha) were measured in rabbit dorsal skin by the use of [131I]-albumin and 133Xe. 2. Little plasma exudation was produced by any of the prostaglandins when injected alone. 3. Both PGE2 and PGI2 were potent at increasing blood flow, whereas PGF2 alpha and PGD2 produced an increase only at high doses. 4. All of the prostaglandins studied potentiated the plasma exudation induced by bradykinin. PGE2 and PGI2 had similar potent potentiating activity, whereas PGD2 and PGF2 alpha had activity at doses too high to be of biological significance. 5. Intradermal injections of arachidonate alone resulted in little plasma exudation but produced an increase in blood flow. Arachidonate potentiated bradykinin-induced plasma exudation. 6. Locally-injected indomethacin had no effect on basal blood flow and little effect on the exudation produced by bradykinin, but indomethacin did inhibit the vasodilatation and exudation potentiation produced by arachidonate. 7. PGE2 and PGI2 had similar potency in producing marked potentiation of plasma exudation induced by intradermal injection of zymosan. 8. In the reaction to zymosan, it is concluded that vasodilatation is the result of the release of arachidonate, which is subsequently coverted to either PGE2 or PGI2. These substances regulate the plasma exudation induced by independently-released vascular permeability-increasing mediators.
Topics: Animals; Arachidonic Acids; Blood Vessels; Bradykinin; Epoprostenol; Indomethacin; Inflammation; Injections, Intravenous; Injections, Subcutaneous; Male; Prostaglandins; Prostaglandins E; Rabbits; Regional Blood Flow; Zymosan
PubMed: 371730
DOI: 10.1111/j.1476-5381.1979.tb07860.x -
British Journal of Pharmacology Aug 1985The abilities of prostaglandin E1 (PGE1), PGE2, PGD2 and PGF2 alpha to antagonize striatal dopamine function were assessed following bilateral and unilateral injections...
The abilities of prostaglandin E1 (PGE1), PGE2, PGD2 and PGF2 alpha to antagonize striatal dopamine function were assessed following bilateral and unilateral injections into the striata of the rat and guinea-pig. Three tests were used to assess the effects of the bilateral injections, ability to antagonize dyskinetic biting induced by 2-di-n-propylamino-5,6-dihydroxytetralin (0.025 mg kg-1 s.c.), ability to antagonize stereotyped behaviour induced by apomorphine (0.5 or 2 mg kg-1 s.c.) and ability to induce catalepsy. Asymmetry/circling behaviour revealed on challenge with apomorphine (0.25 mg kg-1 s.c.) was measured following unilateral injection into the striatum. In the rat, dyskinetic biting induced by 2-di-n-propylamino-5,6-dihydroxytetralin was antagonized by PGE1 (0.001-1 micrograms) and PGE2 (0.00001-1 micrograms) but not by PGD2 or PGF2 alpha (1 microgram). Stereotyped behaviour induced by apomorphine was not antagonized by any of the prostaglandins. A weak catalepsy was induced by PGE1 (1 microgram only), PGE2 (0.001-1 micrograms) and PGD2 (0.001-1 micrograms) but not by PGF2 alpha. Asymmetry and circling behaviour was only observed following the unilateral injection into the striatum of PGE1 and PGD2 (0.01-1 microgram) and challenge with apomorphine. In the guinea-pig the actions of PGE1 and E2 were compared with those of PGF2 alpha. Dyskinetic biting induced by 2-di-n-propylamino-5,6-dihydroxytetralin was antagonized by bilateral injections into the striatum of PGE2 (0.001-1 microgram), but not PGE1 (0.5 micrograms) and PGF2 alpha (1 microgram) but not PGE, (0.5 micrograms) and PGF2 alpha (1 microgram). Similar injections of PGE1, E2 and F2 alpha, all failed to antagonize apomorphine-induced stereotyped behaviour, or to induce catalepsy. PGE, (0.01-0.5 fig) and PGE2 (0.002-1 pg), but not PGF2 alpha, caused asymmetry following unilateral injection into the striatum and peripheral challenge with apomorphine. 5 It is concluded that the major effect in the striatum of the prostaglandins of the E series is to antagonize dyskinetic biting; this action is not shared by other prostaglandins tested, and does not reflect a generalised ability to antagonize striatal dopamine function. It is suggested that the actions of the prostaglandins to modify differentially dopamine-dependent behaviours from the striatum may reflect activity at a site subsequent to the dopamine receptor.
Topics: Alprostadil; Animals; Apomorphine; Corpus Striatum; Dinoprost; Dinoprostone; Dopamine; Dyskinesia, Drug-Induced; Functional Laterality; Guinea Pigs; Male; Prostaglandin D2; Prostaglandins D; Prostaglandins E; Prostaglandins F; Rats; Rats, Inbred Strains; Receptors, Dopamine; Stereotyped Behavior; Tetrahydronaphthalenes
PubMed: 3862460
DOI: 10.1111/j.1476-5381.1985.tb11095.x -
The Journal of Investigative Dermatology Oct 1986We have recently shown that the novel neuropeptide calcitonin gene-related peptide, CGRP, is a potent vasodilator. In this paper we report a detailed study of the... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
We have recently shown that the novel neuropeptide calcitonin gene-related peptide, CGRP, is a potent vasodilator. In this paper we report a detailed study of the effects of CGRP in human skin. CGRP induces a clearly defined, long-lasting erythema. We have measured the effect of CGRP on blood flow in human skin using a laser Doppler technique and have demonstrated increased local blood flow that persists for a number of hours. We compared the response of CGRP with other known vasodilators [histamine, prostaglandin (PG) E2, PGI2, substance P, and vasoactive intestinal peptide (VIP)] in the skin, and in all subjects the erythema induced by CGRP was more persistent than that induced by the other mediators tested. Except at high doses the local vasodilatation induced by CGRP was not associated with a wheal and flare as seen with histamine, substance P, and VIP. CGRP is an extremely potent vasodilator and if released into the circulation, or locally from peripheral nerve endings, it could have a role in the regulation of blood flow in both physiologic and pathologic conditions; CGRP may be the endogenous mediator of the flare in the triple response. A deficiency in CGRP secretion or action could be an important component of peripheral vascular disease. Some flushing reactions (e.g., those associated with medullary thyroid carcinoma) may result from circulating CGRP.
Topics: Adult; Calcitonin Gene-Related Peptide; Dinoprostone; Dose-Response Relationship, Drug; Female; Histamine H1 Antagonists; Humans; Male; Neuropeptides; Prostaglandins E; Regional Blood Flow; Skin; Substance P; Vasoactive Intestinal Peptide; Vasodilator Agents
PubMed: 2428885
DOI: 10.1111/1523-1747.ep12455620