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

Abstract

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...

Possible role of leukotrienes in hypoxic contraction of canine isolated basilar artery

“…Previous studies have shown that this hypoxia-induced contraction was not due to adrenergic, muscarinic, histaminergic or 5-hydroxytryptaminergic mechanisms, nor was it due to the release of prostaglandins (Mallick et al, 1987 (Kito et al, 1981;Michelassi et al, 1982;Kopia et al, 1987) and cerebral arteries of several species including man (Tagari et al, 1983;Rosenblum, 1985;Busija et al, 1986;Jancar et al, 1987;Nishiye et al, 1988). In agreement with other authors, we have also noted the constrictor effect of leukotrienes on canine isolated basilar artery rings.…”

Factors inducing endothelium‐dependent relaxation in the guinea‐pig basilar artery as estimated from the actions of haemoglobin

“…Most of these substances except for endothelium-derived contracting factor tend to produce relaxation of vascular tissues. Cerebral vasospasm, occurring following subarachnoid haemorrhage, may be partly caused by synthesis of thromboxane A2 or leukotriene D4 (Tagari et al, 1983;Rosenblum, 1985;Busija et al, 1986) by the platelets, leucocytes and erythrocytes contained within the clot (coagulate). Thus, Hb contained in the clot may act as a stimulant of vascular smooth muscle cells and also as an inhibitor of EDRF-induced relaxation, so causing vasoconstriction.…”

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

“…Leukotriene D4 (LTD4), a component of slow reactand cerebral arteries of several species including man ing substance of anaphylaxis, is a product of arachi-(coronary artery: Kito et al, 1981;Michelassi et al, donic acid via 5-lipoxygenase and has received much 1982; Piper & Stewart, 1986;Kopia et al, 1987, attention as the putative mediator of bronchconstriccerebral artery: Tagari et al, 1983;Rosenblum, tion in asthma and anaphylaxis (Hedqvist et al, 1985;Busija et al, 1986). …”