Leukotriene D4 relaxes canine renal and superior mesenteric arteries.

Secrest, Roberta J.; Olsen, E J; Chapnick, B. M.

doi:10.1161/01.res.57.2.323

Cited by 47 publications

(21 citation statements)

References 24 publications

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“…Moreover, recent sturlies showed endothelium-dependent relaxing capacity for LTD4 on precontracted blood vessels (28). Again, the relaxing activity of L Ts in such preparations were independent of arachidonate metabolites.…”

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confidence: 88%

Systemic and regional hemodynamic effects of leukotrienes D4 and E4 in the conscious rat

Eimerl¹,

Sirén²,

Feuerstein³

1986

American Journal of Physiology-Heart and Circulatory Physiology

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regional hemodynamic effects of leukotrienes D .. and E 4 in the conscious rat. Am. J. Physiol. 251 (Heart Circ. Physiol. 20): H700-H709, 1986.-The effect of leukotrienes (L Ts) D4 and E 4 on systemic and regional hemodynamic variables were studied in the conscious rat (n =5-9). Renal (R) , mesenteric (M), and hindquarter (HQ) blood flow (BF) were monitored by directional pulsed Doppler velocimetry, and mean arterial blood pressure (MAP) and heart rate were recorded through a catheter in the femoral artery. In a separate series of experiments, cardiac index (CI) was measured by the thermodilution method. Systemic injection of LTD 4 or LTE 4 (0.1-10 ~g/kg) produced dose-dependent pressor responses; BF in the M, HQ, and R vessels declined, due to increased vascular resistance (VR) at the following order: M >> HQ > R. Low doses of L TD4 or L TE4 produced vasodilation in the HQ area. Infusion ofLTD4 (3 /J.g· kg-1 ·min-1 ) for 10 min produced progressive and pronounced vascular constriction in the M and H Q regions along with reduction in BF. The LTD 4 infusionalso markedly decreased CI with a concomitant rise in total peripheral resistance index (TPRI). Indomethacin (5 mg/kg iv) pretreatment did not modify any of the hemodynamic effects of LTD4 or LTE4. FPL 55712 (10 mg/kg iv) and L Y 171883 (30 mg/kg iv), two different LT -receptor antagonists, partially blocked the constriction effects of these LTs. LY 171883, but not FPL 55172, blocked the H Q vasodilation produced by L TE ... L Y 171883 alone increased HQ-BF and reduced HQ-VR. These data indicate that LTD 4 and L TE 4 are potent constrictors of the M vascular bed, but at low doses they also produce dilation of the HQ blood vessels. Furthermore, no escape from the effects of prolonged infusion of the L Ts was demonstrated in this species. Finally, the hemodynamic responses to L TD 4 and LTE 4 in the conscious rat are independent of cyclooxygenase products of L Ts and are only partially blocked by FPL 55712 or L Y 171883. These studies taken together suggest a differential distribution of multiple L T receptors in the rat vasculature.indomethacin; blood pressure; renal blood flow; mesenteric blood flow; leukotriene antagonists; anaphylactic shock THE PEPTIDOLEUKOTRIENES (LTs) are 5-lipoxygenase metabolites of arachidonic acid, which have been shown to be the active constituents of the slow reacting substance of anaphylaxis (SRS-A) (27). The potent vasoactive properties of the LTs are well established, but major differences occur between various in vitro vs. in vivo preparations and among diverse species (9). Although most normal vascular preparations constrict in response to in vitro LTs (for review see Ref. 9), some reports show H700 the opposite (14,18,19). In most species studied, in vivo L Ts produce a pressor response, but hypotension is the dominant outcome in guinea pigs and rabbits (9). Furthermore, L Ts were shown to produce renal vascular constriction in the anesthetized pig (24) but to produce dilation in the dog (4,8). Thus conflicting results on hem...

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confidence: 88%

Systemic and regional hemodynamic effects of leukotrienes D4 and E4 in the conscious rat

Eimerl¹,

Sirén²,

Feuerstein³

1986

American Journal of Physiology-Heart and Circulatory Physiology

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“…The endothelium derived relaxing factor (EDRF; Furchgott & Zawadzki, 1980;Furchgott, 1984) released spontaneously or after exposure to various agonists from the endothelium, may increase the amount of muscle cyclic GMP through activation of soluble guanylate cyclase (Rapoport et al, 1983;Murad, 1986) and inhibit contractions due to a reduction in the free concentration of Ca2+ in the cytosol Kobayashi et al, 1985;Itoh et al, 1985). An endothelial component in the action of LTD4 in dog renal and mesenteric arteries has been previously reported (Secrest et al, 1985). The LTD4-induced contraction consisted of small phasic and tonic responses and was enhanced after ablation of endothelium.…”

Section: Discussionmentioning

confidence: 99%

Some effects of leukotriene D₄ on the mechanical properties of the guinea‐pig basilar artery

Nishiye

Itoh

Kuriyama

1988

British J Pharmacology

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1 The effects of leukotriene D4 (LTD4) on the mechanical properties of smooth muscle cells from the guinea-pig basilar artery were investigated in whole and chemically skinned muscle strips.2 In strips with an intact endothelium, 5-hydroxytryptamine (5-HT; 10pM), LTD4 and LTC4 (1I M), STA2 (1 nM-IO nM) and high K+ (30 mM-128 mM) generated contractions. These comprised an initial phasic and subsequently generated tonic response with different amplitudes. Acetylcholine (ACh, 0.1-10pM) inhibited and methylene blue (1-101Mm) enhanced the tonic component of these contractions in endothelium-intact muscle strips. In endothelium-denuded tissues, methylene blue had no effect on mechanical responses and ACh produced a further contraction in the presence of LTD4. 3 When the endothelium was removed, the amplitude of contractions induced by all tested stimulants markedly increased. In intact muscle strips, the order of potency for the production of a maximum response was; 128 mm K+ > STA2 > LTD4= LTC4 = 5-HT. Following removal of the endothelium; STA2> 128 mm K' > LTD4 = LTC4 > 5-HT. 4 In endothelium-denuded strips, the selective LTD4 antagonists, ONO-RS-411 and FPL 55712 inhibited the LTD4-induced contraction. In contrast, guanethidine, prazosin, yohimbine, atropine and mepyramine had no effect. Indomethacin and a thromboxane A2(TXA2) antagonist, ONO-3708 also had no effect on LTD4-induced contractions in endothelium-denuded strips. 5 In endothelium-denuded strips, nifedipine inhibited the tonic contraction induced by LTD4 but not the phasic component. In Ca2 +-free solution containing 2 mm EGTA, LTD4 produced only the phasic contractions. 6 In saponin-treated chemically skinned muscle strips, LTD4 had no effect on either the pCatension relationship or on the release of Ca2+ from intracellular stores. However, inositol 1,4,5-trisphosphate released Ca2+ from the stores and 1,2-diolein, an activator of protein kinase C, enhanced the contractions induced by 0.3 yM Ca2 + 7 It was concluded that LTD4 acts on both the endothelium and on the smooth muscle cells of the guinea-pig basilar artery. It stimulates the release of endothelium-derived relaxing factor (EDRF) which tends to inhibit the LTD4-induced contraction. It also interacts with receptors on the smooth muscle and produces a contraction as a result of an increase in both voltage-dependent and receptor-activated Ca2 influx and, in part, the release of Ca2 + from cellular storage sites.

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“…LT have been shown to constrict resistance vessels in coronary (3,5,6), pulmonary (16), and mesenteric (4) circulations, although contradictory evidence has been reported (4,20). In addition, LT also have been reported to increase vascular permeThe specific receptor antagonist FPL 55712 was effective in blocking pial arterial constriction to leukotrienes (Fig.…”

Section: Discussionmentioning

confidence: 99%

Effects of Leukotrienes C4, D4, and E4 on Cerebral Arteries of Newborn Pigs

1986

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Fifteen piglets (four animals were I day old, six were 2 days old, three were 3 days old, and two were 5 days old; 1.1-2.3 kg) Received February 24, 1986; accepted May 21, 1986. Correspondence David W. Busija, Ph.D., Department of Physiology and Biophysics, University of Ten nessee Center for the Health Sciences, 894 Union Avenue (NA 501), Memphis, TN 38163. This work was supported by research Grants HL-30260 and HL-34059 from the National Heart. Lung and Blood Institute, and by Grants-in-Aid from the American Heart Association and Tennessee Heart Association. C.W.L. is an Established Investigator of the American Heart Association with funds contributed in part by the Tennessee Affiliate.ABSTRACT. We examined effects of topical application of leukotrienes (LT) C 4 , D4, and E 4 on cerebral arteries of newborn pigs in vivo. Diameters of pial arteries were measured using a cranial window method during application of artificial cerebrospinal fluid without drug, and cerebrospinal fluid containing LT C, D4, and L (1, ]0, 100, 1000, and 5000 ng/ml). Control diameters ranged from 51-345 JLm. All three LT constricted pial arteries in a dosedependent manner, with a threshold for detectable response at 10 nglml (7 ± 3% for LTD4). The magnitude of constrictor response at the highest dose was 23 ± 3% for LTC4, 17 ± 2% for LTD 4 , and 17 ± 3% for LTE 4 . The specific receptor antagonist FPL 55712 blocked the constrictor response to LT. We conclude that LT are potent constrictors of cerebral arteries in newborn pigs. (Pediatr Res 20: [973][974][975][976]1986) LT are a group of biologically active compounds that are derived from arachidonic acid via the 5-lipoxygenase pathway (I, 2). The peptidoleukotrienes (LTC4, 0 4 , E4, and F4) are synthetized by various peripheral tissues in response to injury (1,2) and have potent effects on vascular tone (3-6) and permeability (7-9). The LT also are synthesized by brain under a variety of pathological conditions (10, 11), but knowledge of the effects of these substances on cerebral vessels is limited and the results are contradictory (12-15). Further, effects of LT on the newborn cerebral circulation have not been investigated. The risk of cerebral trauma during the perinatal period is considerable. LT have potent effects on the pulmonary and systemic circulations in neonatal animals (16). The purpose of this study was to determine effects of LTC4, LT04, and LTE4 on pial arteries of newborn pigs. Pial arteries are important resistance vessels in the cerebral circulation (17).of either sex were used in these experiments. Piglets were anesthetized with ketamine hydrochloride (33 mg/kg, intramuscular) and acepromazine (3.3 mg/kg, intramuscular), and were maintained on a-chloralose (30-50 mg/kg initially, supplemented with 5 mg/kg/h, intravenous). Following a tracheostomy, a tube was placed into the airway and the animals were intubated and ventilated with room air using a Harvard small animal respirator. A catheter was inserted into a femoral artery to record blood pressure and to sam...

show abstract

Leukotriene D4 relaxes canine renal and superior mesenteric arteries.

Cited by 47 publications

References 24 publications

Systemic and regional hemodynamic effects of leukotrienes D4 and E4 in the conscious rat

Systemic and regional hemodynamic effects of leukotrienes D4 and E4 in the conscious rat

Some effects of leukotriene D₄ on the mechanical properties of the guinea‐pig basilar artery

Effects of Leukotrienes C4, D4, and E4 on Cerebral Arteries of Newborn Pigs

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Leukotriene D4 relaxes canine renal and superior mesenteric arteries.

Cited by 47 publications

References 24 publications

Systemic and regional hemodynamic effects of leukotrienes D4 and E4 in the conscious rat

Systemic and regional hemodynamic effects of leukotrienes D4 and E4 in the conscious rat

Some effects of leukotriene D4 on the mechanical properties of the guinea‐pig basilar artery

Effects of Leukotrienes C4, D4, and E4 on Cerebral Arteries of Newborn Pigs

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Some effects of leukotriene D₄ on the mechanical properties of the guinea‐pig basilar artery