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M Indomethacin (m + indomethacin)

Distribution by Scientific Domains

Medical Sciences	100%

Selected Abstracts

Prostanoid release and constrictor responses to noradrenaline in the rat mesenteric vascular bed in non-insulin-dependent diabetes mellitus

AUTONOMIC & AUTACOID PHARMACOLOGY, Issue 3 2001
H. A. Peredo
1,The administration of streptozotocin (STZ) to 2-day old rats induced a non-insulin-dependent diabetes mellitus (NIDDM)-like state, with mild hyperglycaemia and no alterations in body weight at the adult age. 2,In the isolated and perfused mesenteric vascular bed of NIDDM animals, the constrictor responses to either noradrenaline (NA) or potassium chloride (KCl) were not modified as compared with age-matched non-diabetic controls. 3,The reduction in NA contractions induced by the cyclooxygenase inhibitor, 10 ,M indomethacin in the control group was absent in the NIDDM rats. 4,The increase in the NA-induced contractions caused by endothelium removal was suppressed by indomethacin in the controls but not in the NIDDM group. 5,The prostanoid release from the mesenteric vascular beds of NIDDM rats was markedly reduced as compared with non-diabetic controls. Noradrenaline increased production of the constrictor prostaglandin (PG) F2, in control but not in NIDDM rats. 6,In summary, these results show that in STZ-induced NIDDM rats, there is an impairment of the prostanoid production, as well as a suppression of the role of prostanoids in the contractile effects of NA in the mesenteric vascular bed. These alterations are more severe than those previously observed in a model of insulin-dependent diabetes mellitus (IDDM), in which hyperglycaemia and reduction of body weight were more marked. The conclusion is that, in these models of diabetes and in the preparation studied, vascular alterations and modifications of glycaemia and body weight are not closely related. [source]

Mechanisms of 17 ,-oestradiol induced vasodilatation in isolated pressurized rat small arteries

BRITISH JOURNAL OF PHARMACOLOGY, Issue 3 2000
Linda Shaw
The influence of 17 ,-oestradiol on pressurized isolated rat mesenteric and coronary small arteries was investigated. 17 ,-oestradiol caused rapid (t1.0<5 mins) concentration-dependent relaxations of pre-contracted pressurized (50 mmHg) isolated rat mesenteric and coronary arteries. Similar responses were observed in both vessel types. Significant relaxations were only observed at concentrations exceeding 3 ,M. The vasodilatory responses in both types of artery were unaffected by 10 ,ML -nitro arginine (L -NNA) alone or in the presence of 10 ,M indomethacin, inhibitors of nitric oxide and prostaglandin synthesis respectively. They were also unaffected by the pre-contracting agent used i.e. high K+ or U46619 (a thromboxane analogue). Neither the oestrogen receptor antagonist ICI 182,780 (10 ,M) nor the protein synthesis inhibitor cycloheximide (100 ,M) had any effect on the responses of mesenteric arteries to 17 ,-oestradiol. 17 ,-oestradiol had only a minor effect on mesenteric arterial diameter over a concentration range similar to the effective vasodilatory range for 17 ,-oestradiol. Membrane impermeant 17 ,-oestradiol conjugated to bovine serum albumin (,-oestradiol-17hemisuccinate-BSA) (E-H-BSA) resulted in a vasodilatation of pressurized arteries. Wortmannin, an inhibitor of myosin light chain kinase, near maximally relaxed pressurized mesenteric arteries although the time course for the response was significantly slower than that for 17 ,-oestradiol. These results taken together suggest that the acute effects of 17 ,-oestradiol on isolated pressurized arterial tone may be due to effects directly on the vascular smooth muscle via non-genomic mechanisms that involve a stereospecific interaction at the plasma membrane. British Journal of Pharmacology (2000) 129, 555,565; doi:10.1038/sj.bjp.0703084 [source]

Opposite effects of endogenous nitric oxide and prostaglandin F2, in the rat mesenteric bed

AUTONOMIC & AUTACOID PHARMACOLOGY, Issue 3 2003
H. A. Peredo
Summary 1 The relationship between the effects of endogenous nitric oxide (NO) and prostanoids on the noradrenaline (NA)-induced contractions and the mechanisms involved were investigated in the rat perfused mesenteric bed, using NG -nitro- l -arginine methyl ester (l -NAME), a NO synthase inhibitor and sodium nitroprusside (SNP), a NO donor. 2 The constrictor responses to NA were reduced to 50% by the cyclooxygenase inhibitor 10 ,m indomethacin as well as by 1 ,m SNP. When indomethacin and SNP were perfused simultaneously the contractions were further reduced. 3 The NA-induced contractions were increased by the addition of 400 ,ml -NAME and the addition of either indomethacin or SNP abolished such increases. The simultaneous perfusion of both agents further reduced the contractions. 4 Removal of the endothelium increased NA-induced contractions to a similar extent as l -NAME and this increase was abolished by indomethacin as well as by SNP. 5 The perfusion of 10 ,m NA augmented the release of prostaglandin (PG) F2, by the mesenteric bed without modifications in any other prostanoid. In the presence of l -NAME, this effect was further increased. However, SNP abolished the NA-induced stimulation of PGF2, release. 6 In de-endothelialized preparations NA also stimulated PGF2, production as observed in intact preparations. This effect was more marked in the presence of l -NAME; in contrast, SNP abolished the stimulation. 7 In conclusion, the present results suggest an opposite action between NO and PGF2, on the NA-induced contractions in the rat mesenteric bed. [source]

Airway epithelium-derived transforming growth factor-, is a regulator of fibroblast proliferation in both fibrotic and normal subjects

CLINICAL & EXPERIMENTAL ALLERGY, Issue 8 2008
K. E. Hostettler
Summary Background In the healthy lung, airway epithelial cells (AEC) regulate fibroblast proliferation through release of soluble factors, such as prostaglandins and proteins. Fibroproliferative diseases and airway remodelling may result from an inadequate generation of suppressive factors by AEC or the inability of fibroblasts to respond to them appropriately. Objective The aim of this study was to study the effect of primary human AEC on the proliferation of fibroblasts obtained from healthy and fibrotic lungs in an interactive cell culture model. Results Conditioned medium (CM) from 14 out of 16 AEC lines significantly inhibited proliferation of normal human lung fibroblasts by 51.2±6.0%. The proliferation of fibroblasts derived from patients with lung fibrosis was equally inhibited by CM of AEC. The inhibitory effect of AEC-CM was completely reversed when fibroblasts were pre-incubated with 2.5 ,m indomethacin. Furthermore, primary human AEC, but not fibroblasts, secrete TGF-,, and the inhibitory effect of the AEC-CM was blocked by neutralizing anti-TGF-, antibodies. Conclusion These results demonstrate that AEC actively inhibit the proliferation of both normal and fibrotic fibroblasts via TGF-,, which induces the prostaglandin E2 synthesis in fibroblasts. The data indicate that proliferative lung diseases may be treated using the epithelial cell as the target of medication. [source]