Influence of TMB-8 and thapsigargin on vasoconstrictor responses in the pulmonary vascular bed of the cat.
The effects of 8-(diethylamino)octyl-3,4,5-trimethoxybenzoate hydrochloride (TMB-8), a protein kinase C (PKC) inhibitor, and thapsigargin, a CaATPase inhibitor, on pressor responses were studied in the pulmonary vascular bed of the intact-chest anesthetized cat. Under conditions of constant lobar blood flow in the cat, injections of the angiotensin peptides (ANG II), norepinephrine (NE), serotonin (5-HT), Bay K 8644, and the thromboxane A2 mimic U46619 into the lobar arterial perfusion circuit caused dose-related increases in lobar arterial pressure and responses were reproducible with respect to time. Intravenous infusion of TMB-8 at 1.0 mug . kg reduced the pressor response to the ANG II and to NE. However, TMB-8 did not alter pressor responses to 5-HT, U46619, or Bay K 8644. In a separate series of experiments, the effects of thapsigargin were investigated and intravenous infusion of the CaATPase inhibitor at 1.0 mug . kg also reduced pressor responses to the ANG II and to NE but did not alter pressor responses to 5-HT, U46619, and Bay K 8644. The data provide support for the hypothesis that vasoconstrictor responses to ANG II and NE in the pulmonary vascular bed are mediated in part by the activation of protein kinase C (PKC) and sarcoplasmic reticulum CaATPase-sensitive mechanisms in the cat. The present data suggest that pulmonary pressor responses to U46619, 5-HT, and Bay K 8644 are not mediated by PKC or CaATPase activation in the pulmonary vascular bed of the cat.
Ibrahim
Ikhlass N
IN
Department of Anesthesiology, Texas Tech University School of Medicine, Lubbock, Texas, USA.
Hoover
Jason M
JM
Fields
Aaron M
AM
Richards
Todd A
TA
Kaye
Alan D
AD
D000818:Animals; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors*; D002415:Cats; D004305:Dose-Response Relationship, Drug; D005260:Female; D005707:Gallic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D008168:Lung / Q000098:blood supply*; D008297:Male; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D011652:Pulmonary Circulation / Q000187:drug effects; D019284:Thapsigargin / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D014662:Vasoconstrictor Agents; C006014:8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate; D005707:Gallic Acid; D019284:Thapsigargin; D011493:Protein Kinase C; D000252:Calcium-Transporting ATPases