Role of calcium in U 46619 and PGF2 alpha pulmonary vasoconstriction in rat lungs.
The role of calcium and calmodulin during U 46619 and PGF2 alpha-induced pulmonary vasoconstriction was studied in isolated rat lungs perfused with Krebs-Ringer bicarbonate (KRB) or calcium-free KRB. In lungs perfused with KRB, bolus injections of U 46619 (0.2 microgram) and PGF2 alpha (40.0 micrograms) resulted in a 48.0 +/- 4.0 and 23.9 +/- 2.5% increase in mean pulmonary artery pressure, respectively. During lung perfusion with KRB without calcium, the U 46619 response decreased to 31.1 +/- 7.5% whereas the PGF2 alpha response increased to 34.6 +/- 4.1%. Repeated challenges with PGF2 alpha in the KRB without calcium resulted in reduction of the response to 11.8 +/- 1.2%; the U 46619 response was unaltered. The intracellular calcium blocker, 8-(N,N-diethylamino)-octyl-3,4,5, trimethoxybenzoate HCL (TMB-8) significantly attenuated the pressor response to U 46619 at low doses and PGF2 alpha at high doses. The calmodulin inhibitor trifluoperazine (TFP 100 microM) attenuated the vasoconstrictor response to U 46619 by 54%, whereas the PGF2 alpha was unchanged. However, in the calcium-free KRB, TFP attenuated the pressor response to both U 46619 and PGF2 alpha. The U 46619 pressor response depends on intracellular and extracellular calcium to achieve calmodulin-dependent vasoconstriction. PGF2 alpha requires extracellular calcium to replenish depletable intracellular calcium pools and is independent of calmodulin activation.
Santoian
E C
EC
Department of Physiology and Biophysics, Georgetown University Medical Center, Washington, DC 20007.
Angerio
A D
AD
Schneidkraut
M J
MJ
Ramwell
P W
PW
Kot
P A
PA
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002118:Calcium / Q000502:physiology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002147:Calmodulin / Q000502:physiology; D015237:Dinoprost / Q000494:pharmacology*; D005707:Gallic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D066298:In Vitro Techniques; D008168:Lung / Q000098:blood supply; D008297:Male; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology*; D011652:Pulmonary Circulation / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D014268:Trifluoperazine / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects*
D002121:Calcium Channel Blockers; D002147:Calmodulin; D011450:Prostaglandin Endoperoxides, Synthetic; D014268:Trifluoperazine; C006014:8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate; D005707:Gallic Acid; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D015237:Dinoprost; D002118:Calcium