El tratamiento postnatal con melatonina modula la expresión de agentes prostanoides en pulmón de neonatos de oveja con hipertensión pulmonar / Melatonin modulates the expression of pulmonary prostanoids

Background: Living above 2,500 meters in hypobaric conditions induces pulmonary arterial hypertension of the neonate (PAHN), a syndrome whose main features are: pathological remodeling of the pulmonary vessels, abnormal vascular reactivity and increased oxidative stress. Melatonin could have pulmonary antioxidant, anti-remodeling and vasodilating properties for this condition. Aim: To determine the effect of melatonin at the transcript level of prostanoid pathways in the lung of neonatal lambs gestated and born under hypobaric hypoxia. Material and Methods: Vehicle (1.4% of ethanol, n = 6) or melatonin (1 mg * kg1, n = 5) were administered from the postnatal day 4 to 21 to lambs gestated and born at 3,600 meters above sea level. After one week of treatment completion, lung tissue was obtained, the transcript and protein levels of prostanoid synthases and receptors were assessed by RT-PCR and Western Blot. Results: Melatonin induced the expression of prostacyclin synthase transcript and increased protein expression of the prostacyclin receptor. In addition, the treatment decreased the expression of transcript and protein of cyclooxygenase-2, without changes in the expression of the prostanoid vasoconstrictor (thromboxane) pathway. Conclusions: Postnatal treatment with melatonin increases the expression of the prostacyclin-vasodilator pathway without changing the vasoconstrictor thromboxane pathway. Further, the decreased COX-2 induced by melatonin could be an index of lesser oxidative stress and inflammation in the lung.

A Single Resistance Exercise Session Improves Aortic Endothelial Function in Hypertensive Rats / Uma Única Sessão de Exercício Resistido Melhora a Função Endotelial Aórtica em Ratos Hipertensos

Abstract Background: Physical exercise is an important tool for the improvement of endothelial function. Objective: To assess the effects of acute dynamic resistance exercise on the endothelial function of spontaneously hypertensive rats (SHR). Methods: Ten minutes after exercise, the aorta was removed to evaluate the expression of endothelial nitric oxide synthase (eNOS), phosphorylated endothelial nitric oxide synthase (p-eNOS1177) and inducible nitric oxide synthase (iNOS) and to generate concentration-response curves to acetylcholine (ACh) and to phenylephrine (PHE). The PHE protocol was also performed with damaged endothelium and before and after NG-nitro-L-arginine methyl ester (L-NAME) and indomethacin administration. The maximal response (Emax) and the sensitivity (EC50) to these drugs were evaluated. Results: ACh-induced relaxation increased in the aortic rings of exercised (Ex) rats (Emax= -80 ± 4.6%, p < 0.05) when compared to those of controls (Ct) (Emax = -50 ± 6.8%). The Emax to PHE was decreased following exercise conditions (95 ± 7.9%, p < 0.05) when compared to control conditions (120 ± 4.2%). This response was abolished after L-NAME administration or endothelial damage. In the presence of indomethacin, the aortic rings' reactivity to PHE was decreased in both groups (EC50= Ex -5.9 ± 0.14 vs. Ct -6.6 ± 0.33 log µM, p < 0.05 / Emax = Ex 9.5 ± 2.9 vs. Ct 17 ± 6.2%, p < 0.05). Exercise did not alter the expression of eNOS and iNOS, but increased the level of p-eNOS. Conclusion: A single resistance exercise session improves endothelial function in hypertensive rats. This response seems to be mediated by increased NO production through eNOS activation.

Resumo Fundamento: O exercício físico é uma importante ferramenta para o aprimoramento da função endotelial. Objetivo: Avaliar os efeitos do exercício dinâmico resistido agudo na função endotelial de ratos espontaneamente hipertensos (SHR). Métodos: Após 10 minutos de exercício, a aorta foi removida para avaliação da expressão de óxido nítrico sintase endotelial (eNOS), óxido nítrico sintase endotelial fosforilada (p-eNOS1177) e óxido nítrico sintase endotelial induzível (iNOS), e para a construção de curvas concentração-resposta de acetilcolina (ACT) e fenilefrina (FEN). O protocolo FEN foi também realizado com lesão endotelial e antes e depois da administração de N-nitro-L-arginina metil éster (L-NAME) e indometacina. A resposta máxima (Emax) e a sensibilidade (EC50) a esses fármacos foram avaliadas. Resultados: Houve aumento do relaxamento induzido por ACT nos anéis aórticos dos ratos exercitados (Ex) (Emax = -80 ± 4,6%; p < 0,05) quando comparado àquele dos controles (Ct) (Emax = -50 ± 6,8%). A Emax à FEN diminuiu após exercício (95 ± 7,9%; p < 0,05) quando comparada àquela dos controles (120 ± 4,2%). Tal resposta foi abolida após administração de L-NAME ou lesão endotelial. Na presença de indometacina, a reatividade dos anéis aórticos à FEN diminuiu nos dois grupos (EC50= Ex -5,9 ± 0,14 vs. Ct -6,6 ± 0,33 log µM; p < 0,05/ Emax = Ex 9,5 ± 2,9 vs. Ct 17 ± 6,2%; p < 0,05). O exercício não alterou a expressão de eNOS e de iNOS, mas aumentou o nível de p-eNOS. Conclusão: Uma única sessão de exercício resistido melhora a função endotelial em ratos hipertensos. Essa resposta parece ser mediada por elevação da produção de NO através de ativação de eNOS.

Medicina antienvelhecimento: notas sobre uma controvérsia sociotécnica / Anti-aging medicine: notes on a socio-technical controversy

Após algumas décadas de batalha, a geriatria e a gerontologia se tornaram as legítimas ciências do envelhecimento. Hoje surge uma contestação a tal condição. Em sua breve história, a medicina antienvelhecimento se afirmou como prática médica que questiona o modo de se endereçar o envelhecimento biológico. Com isso, toda a medicina é questionada. Aqui, exploramos especialmente como essa controvérsia se estrutura em torno dos fundamentos das ciências do envelhecimento. Há bases para esses questionamentos? Como eles foram tratados por aqueles que os receberam? Tendo em vista uma perspectiva sociotécnica, é interessante pensar que, para geriatras e gerontólogos, a necessária crítica à medicina antienvelhecimento também traz uma importante reflexão sobre o modo como as ciências do envelhecimento vêm tratando seu objeto.

After some decades of struggle, geriatrics and gerontology have become the legitimate sciences of aging. Today, their status is being questioned. In its short history, anti-aging medicine has taken root as a medical practice that questions how to address biological aging. In so doing, all medicine is questioned. Here, we explore in particular how this controversy is structured around the founding principles of the sciences of aging. Is there any basis for these questionings? How have they been treated by those who have received them? Taking a socio-technical viewpoint, it is worth considering that for geriatricians and gerontologists, the need to criticize anti-aging medicine also raises some important reflections about how the sciences of aging address their subject.

Estresse Isolado ou Associado ao Etanol Libera Prostanóides em Aorta de Ratos via ?2-Adrenoceptores / Stress Alone or associated with Ethanol Induces Prostanoid Release in Rat Aorta via ?2-Adrenoceptor

Fundamento: Estresse e etanol são ambos, independentemente, importantes fatores de risco cardiovascular. Objetivo: avaliar o risco cardiovascular do consumo de etanol e exposição ao estresse, isolados e em associação, em ratos machos adultos. Métodos: Os ratos foram separados em quatro grupos: controle, etanol (20% na água de beber durante seis semanas), estresse (imobilização 1h dia/5 dias por semana/ 6 semanas) e estresse/etanol. As curvas de concentração-resposta à noradrenalina - na ausência e na presença de ioimbina, L-NAME ou indometacina - ou fenilefrina foram determinadas em aortas torácicas com e sem endotélio. EC50 e resposta máxima (n = 8-12) foram comparadas através de ANOVA de dois fatores (two-way) / método de Bonferroni. Resultados: Estresse ou estresse em associação com o consumo de etanol aumentaram as respostas máximas de noradrenalina em aortas intactas. Essa hiper-reatividade foi eliminada pela remoção do endotélio, ou pela presença da indometacina ou ioimbina, mas não foi alterada pela presença de L-NAME. Enquanto isso, o consumo de etanol não alterou a reatividade à noradrenalina. As respostas da fenilefrina em aortas com e sem endotélio também permaneceram inalteradas independentemente do protocolo. Conclusão: O estresse crônico aumentou as respostas aórticas dos ratos à noradrenalina. Esse efeito é dependente do endotélio vascular e envolve a liberação de prostanóides vasoconstritores através da estimulação de α-2 adrenoceptores endoteliais. Além disso, o consumo crônico de etanol pareceu não influenciar as respostas de noradrenalina em aorta de rato, nem modificar o aumento de tais respostas observadas em consequência da exposição ao estresse. .

Background: Stress and ethanol are both, independently, important cardiovascular risk factors. Objective: To evaluate the cardiovascular risk of ethanol consumption and stress exposure, isolated and in association, in male adult rats. Methods: Rats were separated into 4 groups: Control, ethanol (20% in drinking water for 6 weeks), stress (immobilization 1h day/5 days a week for 6 weeks) and stress/ethanol. Concentration-responses curves to noradrenaline - in the absence and presence of yohimbine, L-NAME or indomethacin - or to phenylephrine were determined in thoracic aortas with and without endothelium. EC50 and maximum response (n=8-12) were compared using two-way ANOVA/Bonferroni method. Results: Either stress or stress in association with ethanol consumption increased the noradrenaline maximum responses in intact aortas. This hyper-reactivity was eliminated by endothelium removal or by the presence of either indomethacin or yohimbine, but was not altered by the presence of L-NAME. Meanwhile, ethanol consumption did not alter the reactivity to noradrenaline. The phenylephrine responses in aortas both with and without endothelium also remained unaffected regardless of protocol. Conclusion: Chronic stress increased rat aortic responses to noradrenaline. This effect is dependent upon the vascular endothelium and involves the release of vasoconstrictor prostanoids via stimulation of endothelial alpha-2 adrenoceptors. Moreover, chronic ethanol consumption appeared to neither influence noradrenaline responses in rat thoracic aorta, nor did it modify the increase of such responses observed as a consequence of stress exposure. .

Métodos de indução do trabalho de parto / Methods of induction of labour

Os métodos de indução do parto podem ser divididos em estímulos naturais, estímulos exógenos diretos ou mecânicos e estímulos exógenos indiretos ou farmacológicos, cada qual apresenta suas particularidades nas indicações e contraindicações. O objetivo deste artigo foi realizar uma revisão da literatura consultando Medline/Pubmed e a Biblioteca Cochrane para avaliar a eficácia e segurança na utilização dos principais métodos de indução do trabalho de parto. Apurou-se não haver método ideal de indução do trabalho de parto. Os estímulos naturais e os métodos alternativos carecem de maiores estudos para incentivo de seu uso rotineiro. As prostaglandinas, em destaque o misoprostol, está indicada no Índice de Bishop desfavorável e a ocitocina em condições cervicais favoráveis. Os avanços no campo da biologia molecular tem corroborado que o método ideal deve atuar em sincronismo com a contratilidade uterina e a maturação cervical.(AU)

Methods of labor induction can be classified as natural stimuli, direct exogenous stimuli or mechanical and indirect exogenous stimuli or pharmacological. Which one has its peculiarities in relation to indications and contraindications. The objective of this article was to assess the efficacy and safety of the main methods of induction of labor trough the analysis of the medical literature in Medline/Pubmed and the Cochrane Library to. No ideal method of inducing labor was found. Further studies are required to encourage natural stimuli and alternative methods more often. According to Bishop scores, prostaglandins, (especially misoprostol) are unfavorable and oxytocin in case of favorable cervical environment. Advances in the field of molecular biology have confirmed that the ideal method should work simultaneously with uterine contraction and cervical ripening.(AU)

Mast Cells in Allergic Asthma and Beyond

Mast cells have been regarded for a long time as effector cells in IgE mediated type I reactions and in host defence against parasites. However, they are resident in all environmental exposed tissues and express a wide variety of receptors, suggesting that these cells can also function as sentinels in innate immune responses. Indeed, studies have demonstrated an important role of mast cells during the induction of life-saving antibacterial responses. Furthermore, recent findings have shown that mast cells promote and modulate the development of adaptive immune responses, making them an important hinge of innate and acquired immunity. In addition, mast cells and several mast cell-produced mediators have been shown to be important during the development of allergic airway diseases. In the present review, we will summarize findings on the role of mast cells during the development of adaptive immune responses and highlight their function, especially during the development of allergic asthma.

Possible Role of Heme Oxygenase-1 and Prostaglandins in the Pathogenesis of Cerebral Malaria: Heme Oxygenase-1 Induction by Prostaglandin D2 and Metabolite by a Human Astrocyte Cell Line

Astrocytes are the most abundant cells in the central nervous system that play roles in maintaining the blood-brain-barrier and in neural injury, including cerebral malaria, a severe complication of Plasmodium falciparum infection. Prostaglandin (PG) D2 is abundantly produced in the brain and regulates the sleep response. Moreover, PGD2 is a potential factor derived from P. falciparum within erythrocytes. Heme oxygenase-1 (HO-1) is catalyzing enzyme in heme breakdown process to release iron, carbon monoxide, and biliverdin/bilirubin, and may influence iron supply to the P. falciparum parasites. Here, we showed that treatment of a human astrocyte cell line, CCF-STTG1, with PGD2 significantly increased the expression levels of HO-1 mRNA by RT-PCR. Western blot analysis showed that PGD2 treatment increased the level of HO-1 protein, in a dose- and time-dependent manner. Thus, PGD2 may be involved in the pathogenesis of cerebral malaria by inducing HO-1 expression in malaria patients.

Role of Prostaglandins in Colon Cancer / 대한소화기학회지

Colon cancer is one of the major leading causes of cancer-related deaths in the Western countries. In Korea, the incidence of colon cancer is increasing due to changes in environment and lifestyle such as diet. Chemoprevention strategy using non-steroidal anti-inflammatory drugs (NSAIDs) has been under intensive clinical and epidemiological research as these drugs suppress colorectal cancer. The best known targets of NSAIDs are cyclooxygenase (COX) enzymes, which convert arachidonic acid to prostaglandins (PGs) and thromboxane. Among these PGs, prostaglandin E2 (PGE2) can promote tumor growth by binding its receptors and activating signal pathways which control cell proliferation, migration, apoptosis, and angiogenesis. Therefore, COX inhibition is promising approach for chemoprevention of colorectal cancer. However, the prolonged use of COX-2 inhibitors is associated with unacceptable cardiovascular side effects. Thus, new targets involved in PGs metabolism are under investigation. 15-hydroxyprostaglandin dehydrogenase (15-PGDH), a key metabolic enzyme of PGE2, was up-regulated in normal colonic epithelium, but decreased in colon cancer. Recent findings suggest that 15-PGDH is involved in the neoplastic progression of initiated colonic epithelial cells. Also, new players related with PGs metabolism including prostaglandin transporter (PGT) and microsomal prostaglandin E synthase (mPGES) were reported to play a role in colorectal cancer development. This review presents current knowledge about the role of prostaglandins and associated proteins in colorectal cancer development and progression.

Effects of cyclo-oxygenase and thromboxane synthetase inhibitors on right atrial prostaglandins.

OBJECTIVES: The aim of this study was to find out the effects of cyclo-oxygenase and thromboxane synthetase inhibitors on right atrial prostacyclin and thromboxane A2 levels. METHODS: The study consisted of a total of 50 patients subjected to coronary bypass surgery. These patients were divided into two groups, Group I and Group II each consisting of 25 patients. In Group I patients, the right atrial tissues were studied for effects of indomethacin and U63557A on the prostaglandin levels. In Group II patients, the right atrial tissues were studied for effects of Aspirin and U63557A on the prostaglandin levels. RESULTS: In Group I patients, the atrial tissues pretreated with indomethacin showed a fall in the levels of 6 keto PGF1 alpha from 153.5 +/- 28.4 pg/0.1 mg to 59.7 +/- 11.6 pg/0.1 mg and of TXB2 from 41.6 +/- 1.2 pg/0.1 mg to 17.2 +/- 3.2 pg/0.1 mg. In the atrial tissues of Group I treated with U63557A the levels of 6 keto PGF1 alpha fell to 145.4 +/- 26.8 pg/0.1 mg and the levels of TXB2 fell to 14.7 +/- 2.8 pg/0.1 mg. In Group II patients, the atrial tissues pretreated with aspirin, showed a fall in the levels of 6 keto PGF1 alpha from 142.1 +/- 2.8 pg/0.1 mg to 17.5 +/- 0.8 pg/0.1 mg. In the atrial tissues pretreated with U63557A, the levels of 6 keto PGF1 alpha fell to 131.2 +/- 2.9 pg/0.1 mg and the levels of TXB2 fell to 14.4 +/- 0.7 pg/0.1 mg. CONCLUSIONS: The study showed that human right atrial tissues are capable of producing TXA2 in addition to prostacyclin. Indomethacin and aspirin by inhibiting generation of cyclic endoperoxides inhibited synthesis of both prostacyclin and TXA2. In contrast a thromboxane synthethase inhibitor U63557A selectively inhibited TXA2 without significant effects on prostacyclin synthesis.

Prostaglandinas menstruales y disminorrea su modulacion por antiiflamatorios no esteroideos / Menstrual prostaglandins and dymenorrhea: modulation by non-steroidal antinflammatory drugs

Se estudió con un diseño prospectivo, doble ciego cruzado, la eficacia y tolerancia analgésica y las modificaciones de las prostaglandinas menstruales inducidas por clonixinato de lisina (CL), controlado con ibuprofeno (I) y placebo (P). El tratamiento comprendió 4 ciclos consecutivos: en el primero todas las pacientes se abstuvieron de tomar medicación; en los tres restantes recibieron dosis fijas, doble ciego de 1 comprimido cada 6 horas conteniendo CL 125 mg o 1 400 mg o P en orden al azar, desde 3 días antes del comienzo de la menstruación por un lapso de 8 días. Se efectuaron controles en cada menstruación evaluándose el dolor en escala de 0 a 4, aparición del síntoma premenstrual e intramenstrual, grado de alivio y aparición de efectos adversos. Durante las menstruaciones las pacientes registraron en un diario sus autoevaluaciones de dolor y recolectaron todo el sangrado menstrual durante los 3 primeros días. La intensidad del dolor menstrual no experimentó cambios entre el control de ingreso (3.16) y el del ciclo sin medicación (3.04), pero disminuyó significativamente con P(2.4), CL (1.79) e I (1.54). Los ciclos con medicación activa mostraron intensidades de dolor significativamente menores que con P. Con P 42 por ciento refirieron dolor premenstrual, que se redujo significativamente al 17 por ciento (CL) y a 12,5 por ciento (I). En los ciclos con activo un 21 por ciento estuvieron asintomáticas durante el período premenstrual y menstrual y un 71 por ciento (CL) y 75 por ciento (I) alivio parcial. El diario de la paciente arrojó una reducción significativa con CL e I durante el 1ro. y 2do. día respecto del P, estas diferencias fueron reduciéndose hasta desaparecer al 4to. día. Los niveles de Pgs menstruales variaron paralalelamente con las intensidades de dolor con reducción respecto al basal de 29 por ciento para P (NS); 58 por ciento para CL y 61 por ciento para I, resultados ambos significativos, p<0.01.

Role of non-nitric oxide non-prostaglandin endothelium-derived relaxing factor(s) in bradykinin vasodilation

The most conspicuous effect of bradykinin following its administration into the systemic circulation is a transient hypotension due to vasodilation. In the present study most of the available evidence regarding the mechanisms involved in bradykinin-induced arterial vasodilation is reviewed. It has become firmly established that in most species vasodilation in response to bradykinin is mediated by the release of endothelial relaxing factors following the activation of B2-receptors. Although in some cases the action of bradykinin is entirely mediated by the endothelial release of nitric oxide (NO) and/or prostacyclin (PGI2), a large amount of evidence has been accumulated during the last 10 years indicating that a non-NO/PGI2 factor accounts for bradykinin-induced vasodilation in a wide variety of perfused vascular beds and isolated small arteries from several species including humans. Since the effect of the non-NO/PGI2 endothelium-derived relaxing factor is practically abolished by disrupting the K+ electrochemical gradient together with the fact that bradykinin causes endothelium-dependent hyperpolarization of vascular smooth muscle cells, the action of such factor has been attributed to the opening of K+ channels in these cells. The pharmacological characteristics of these channels are not uniform among the different blood vessels in which they have been examined. Although there is some evidence indicating a role for KCa or KV channels, our findings in the mesenteric bed together with other reports indicate that the K+ channels involved do not correspond exactly to any of those already described. In addition, the chemical identity of such hyperpolarizing factor is still a matter of controversy. The postulated main contenders are epoxyeicosatrienoic acids or endocannabinoid agonists for the CB1-receptors. Based on the available reports and on data from our laboratory in the rat mesenteric bed, we conclude that the NO/PGI2-independent endothelium-dependent vasodilation induced by BK is unlikely to involve a cytochrome P450 arachidonic acid metabolite or an endocannabinoid agonist.

Mechanism of intragastric amoxicillin protection against 96 percent ethanol damage in rat stomach

The purpose of this study was to investigate the role played by endogenous prostaglandins, sulfhydryls, gastric motility, fluid volume, and mucus volume retained in the gastric lumen in the protection offered by intragastric amoxicillin against ethanol-induced gastric lesions. It has been demonstrated that intragastric administration of amoxicillin (Amx) dose-dependently protected the rat gastric mucosa from 96 per cent ethanol-induced lesions. The inhibition of the lesions was 28, 41.4, 84.7 and 90 per cent at doses of 50, 100, 200 and 400 mg/Kg, respectively. The gastroprotective effect of Amx was significantly reversed by pretreatment with both indomethacin (5 mg/Kg, subcutaneously), a cyclooxygenase inhibitors, and iodoacetamide (100 mg/Kgm subcutaneously), a sulfhydryl blocker. Gastric motility was measured by a ballon method. There was not any significant differences between Amx (50-400 mg/Kg)-induced and spontaneous motility with regard to both amplitudes and frequently of gastric contraction. One milliliter of 96 per cent ethanol produced hemorrhagic bandlike lesions in the corpus mucosa with the occurrence of a complete inhibition of the amplitude and frequency of gastric contraction. This inhibition of gastric motility caused by ethanol was not modified by pretreatment of Amx (400 mg/Kg) alone, indomethacin plus Amx or iodoacetamide plus Amx. In addition, there was a significant increase in the mucus volume retained in the gastric lumen for Amx (200 and 400 mg/Kg) at 30 min after its adminitration. We conclude that the intragastric Amx prospective effect aginst 96 per cent athanol-induced mucosal lesions may be mediated by endogenous prostaglandins, sulfhydryl compounds of the gastric mucosa, an increase in mucus volume retained in the gastric lumen at the time when ethanol is administered, and is not associated with the gastric motor activity.

Systemic prostacyclin in cirrhotic patients

A study of urinary excretion of 6-ketoprostaglandin F1oc in cirrhotic patients as a reliable index of systemic prostacyclin was done in order to understand the mechanism responsible for renal vascular homeostasis in cirrhotic patients. The study was done on 20 patients with cirrhosis and 20 control normal children. Patients without ascites and ascitic patients without renal failure showed increased urinary excretion of immunoreactive 6-ketoprostaglandin F1oc that was believed to reflect renal prostaglandin production and was found to be significantly increased in patients without ascites and in ascetic patients with preserved renal function. Increased renal production of vasodilator prostaglandin in cirrhosis was commonly interpreted as a defence against vasoconstrictor influences on renal hemodynamics. Enhanced renal prostaglandin synthesis in cirrhosis occurs either independently of elevated vasoconstrictor hormones or the activated vasoconstrictor systems enhance prostaglandin synthesis as a compensatory mechanism

Aterosclerose e ácidos graxos ômega-3 / Atherosclerosis and omega-3 fatty acid

Os autores apresentam uma revisäo da aterosclerose e ácidos graxos ômega-3. Têm por objetivo chamar a atençäo para um alimento näo muito consumido pela populaçäo brasileira e, segundo muitos pesquisadores, com propriedades que podem ajudar na prevençäo da aterosclerose - o PEIXE

Avanços terapêuticos em cardiologia. Parte 7: prostaglandinas / Therapeutic development in cardiology. Part 7: prostaglandins

Os autores assinalam as principais indicaçöes das prostaglandinas em cardiologisa. Há dois grupos principais desta droga: vasodilatadoras - PG12,PG13 e PGE2, e vasoconstritoras - TXA2, PGE1 e PGF2alfa, mostram sua importância no mecanismo de açäo de drogas como a furosemida. As principais aplicaçöes das prostaglandinas dizem respeito a várias condiçöes: doença isquêmica, hipertensäo arterial, cardiopatia congênita, insuficiência cardíaca e cirurgia cardíaca. As prostaglandinas constituem um marco na cardiologia moderna

Possible prostaglandin-dopamine interactions during experimental gastric ulcer formation.

The effects of dopamine (DA) agonists and antagonists were investigated on indomethacin--and restraint stress (6 hr at RT)--induced gastric ulcer formation in rats. The DA-agonists, apomorphine and bromocryptine (both at 5 mg/kg) significantly attenuated the frequency and severity of gastric mucosal lesions in both experimental models. The DA-antagonist, haloperidol (0.05 and 1.0 mg/kg) aggravated the gastric ulcerogenesis of both indomethacin and stress, the effects with the lower dose being statistically significant. Haloperidol (0.05 mg/kg) also prevented the cytoprotective effects of apomorphine on indomethacin-ulcers. The atypical DA-antagonist, sulpiride (10 and 50 mg/kg), however, showed differential dose- and model-specific effects. Whereas, the lower dose attenuated indomethacin-ulcers, the higher dose (50 mg/kg) tended to aggravate this phenomenon. The trend of results were reversed in the restraint stress model. Indomethacin (1 mg/kg) aggravated stress-ulcers, an effect which was also appreciably neutralised by apomorphine (5 mg/kg) pretreatment. These results are discussed in light of possible prostaglandin-DA interactions during such experimental gastric pathology.