Influence of protein kinase C inhibitors on vasoconstrictor responses in the pulmonary vascular bed of cat and rat.
The effects of staurosporine and calphostin C, two different protein kinase C (PKC) inhibitors, on pressor responses were studied in the pulmonary vascular bed of the intact chest anesthetized cat and the isolated rat lung. Under conditions of constant lobar blood flow in the cat, injections of the angiotensin peptides, norepinephrine (NE), serotonin, and U-46619 into the lobar arterial perfusion circuit caused dose-related increases in lobar arterial pressure and responses were reproducible with respect to time. Infusion of staurosporine into the perfused lobar artery at 1-2 micrograms/kg for 10 min reduced the pressor response to the angiotensin peptides and to NE; however, staurosporine did not alter pressor responses to serotonin or to the thromboxane mimic U-46619. In a separate series of experiments, the effects of calphostin C were investigated and infusion of the PKC inhibitor into the perfused lobar artery at 1-5 micrograms/kg for 10 min also reduced pressor responses to the angiotensin peptides and to NE and did not alter pressor responses to serotonin or to U-46619. In the isolated rat lung, the inhibitory effects of staurosporine on pulmonary pressor responses were investigated and injections of angiotensin II, NE, and serotonin produced dose-related increases in pulmonary arterial perfusion pressure that were decreased after administration of 20 micrograms ia of the PKC inhibitor staurosporine. (ABSTRACT TRUNCATED AT 250 WORDS)
Kaye
A D
AD
Department of Anesthesiology, Tulane University Medical Center, New Orleans, Louisiana 70112-2699.
Nossaman
B D
BD
Ibrahim
I N
IN
Feng
C J
CJ
Kadowitz
P J
PJ
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000470:Alkaloids / Q000494:pharmacology*; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D002415:Cats; D005260:Female; D008168:Lung / Q000098:blood supply*; D008297:Male; D009281:Naphthalenes; D009638:Norepinephrine / Q000494:pharmacology; D011083:Polycyclic Compounds / Q000494:pharmacology*; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000494:pharmacology; D019311:Staurosporine; D013928:Thromboxane A2 / Q000031:analogs & derivatives / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects*
D000470:Alkaloids; D009281:Naphthalenes; D011083:Polycyclic Compounds; D011450:Prostaglandin Endoperoxides, Synthetic; D000804:Angiotensin II; D012701:Serotonin; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D011493:Protein Kinase C; D019311:Staurosporine; C058819:calphostin C; D009638:Norepinephrine