Hemodynamic effects of leukotriene (LT) D4 and a LTD4 receptor antagonist in the pig.
Vascular bed reactivity to exogenous LTD4 and blockade of these responses by a selective LTD4 receptor antagonist, SK&F 104353, were studied. Yorkshire pigs (N = 13; 25.8 +/- 1.4 kg) were anesthetized with isoflurane, and monitored for cardiac output (CO), mean pulmonary artery pressure (MPAP), pulmonary capillary wedge pressure (PCWP), right ventricular stroke work (RVSW), mean arterial pressure (MAP), renal artery blood flow (RABF), pulmonary vasculature resistance (PVR), renal vascular resistance (RVR), and systemic vascular resistance (SVR). LTD4 (0.03, 0.1, 0.3, 1, 3 and 10.0 micrograms/kg) was given intravenously. The MPAP, MAP, and RABF were recorded at baseline and for 20 min after the injection of LTD4. SK&F 104353 was infused (3 mg/kg/h, i.v.) and the dose-response to LTD4 was repeated. LTD4 induced changes in the MPAP, PCWP, MAP, and RABF. SK&F 104353 attenuated LTD4 induced changes in the MPAP, PVR, RABF and RVSW. MPAP was increased 123 +/- 24% and 115 +/- 10%, respectively, in pigs given 3.0 and 10 micrograms/kg doses, and increased to only 36 +/- 9% at a 10 micrograms/kg dose of LTD4 in animals pretreated with SK&F 104353 (P less than 0.05). MPAP was not increased at the 3.0 micrograms/kg dose, and increased to only 36 +/- 9% at a 10 micrograms/kg dose of LTD4 in animals pretreated with SK&F 104353 (P less than 0.05). These changes were paralleled by a reduction in PVR. RABF was decreased 76 +/- 5% and 83 +/- 7%, respectively, at the 3.0 and 10 micrograms/kg dose of LTD4.(ABSTRACT TRUNCATED AT 250 WORDS)
Zellner
J L
JL
Department of Surgery, Medical University of South Carolina, Charleston 29425.
Cook
J A
JA
Reines
D H
DH
Wise
W C
WC
Smith
E F
EF
Kessler
L D
LD
Halushka
P V
PV
D000818:Animals; D003998:Dicarboxylic Acids / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006439:Hemodynamics / Q000187:drug effects*; D007530:Isoflurane / Q000494:pharmacology; D007700:Kinetics; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors*; D018077:Receptors, Leukotriene; D013189:SRS-A / Q000494:pharmacology*; D013552:Swine
D003998:Dicarboxylic Acids; D011971:Receptors, Immunologic; D018077:Receptors, Leukotriene; D013189:SRS-A; D007530:Isoflurane; C052393:pobilukast