Indomethacin enhances histamine-induced pulmonary hemodynamic changes.
To determine the role of prostaglandins in porcine pulmonary hemodynamic changes caused by histamine, we compared responses to intravenous histamine with and without pre-treatment with the cyclo-oxygenase inhibitor, indomethacin. In anesthetized pigs, pulmonary artery pressure (Ppa), pulmonary arterial wedge pressure (Ppaw), left ventricular end diastolic pressure (Plved) and cardiac output (Q) were measured repeatedly for 30 minutes, following a 1 ml intrajugular injection of histamine 0.6 microM/kg (n = 6), the identical histamine dose after pre-treatment with indomethacin 5 mg/kg (n = 7), or normal saline (n = 5). Pulmonary arterial resistance (Ra) and pulmonary venous resistance (Rv) were calculated as (Ppa-Ppaw)/Q and (Ppaw-Plved)/Q respectively. Indomethacin pre-treatment caused 2-fold greater increases in Ra and Rv with histamine and more prolonged changes. We conclude that inhibition of a vasodilatory prostaglandin released from pulmonary endothelial cells results in unopposed pulmonary vasoconstriction, thereby augmenting pulmonary resistance changes due to histamine.
Tsang
J Y
JY
UBC Pulmonary Research Laboratory, Vancouver, Canada.
Ohtaka
H
H
Ohgami
M
M
Schellenberg
R R
RR
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D004357:Drug Synergism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006632:Histamine / Q000008:administration & dosage / Q000494:pharmacology*; D007213:Indomethacin / Q000008:administration & dosage / Q000494:pharmacology*; D011453:Prostaglandins / Q000378:metabolism; D011652:Pulmonary Circulation / Q000187:drug effects* / Q000502:physiology; D013552:Swine; D014655:Vascular Resistance / Q000187:drug effects
D011453:Prostaglandins; D006632:Histamine; D007213:Indomethacin