Comparison of responses to siguazodan, rolipram, and zaprinast in the feline pulmonary vascular bed.
The present study was undertaken to investigate and compare responses to the cyclic nucleotide phosphodiesterase inhibitors siguazodan (type III, guanosine 3',5'-cyclic monophosphate (cGMP)-inhibited adenosine 3',5'-cyclic monophosphate (cAMP)), rolipram (type IV, cAMP-specific), and zaprinast (type V, cGMP-specific) in the feline pulmonary vascular bed. When tone in the pulmonary vascular bed was raised to a high steady level with a constant infusion of the thromboxane mimic U46619 (9,11-dideoxy-11, alpha9alpha-epoxymethano prostaglandin F(2alpha)), intralobar injections of the three phosphodiesterase inhibitors caused dose-related decreases in lobar arterial pressure. In terms of relative vasodilator activity, rolipram was more potent at higher doses than siguazodan, which was more potent than zaprinast. The duration of the pulmonary vasodilator response to zaprinast was shorter than for siguazodan or rolipram. Furthermore, siguazodan and rolipram, but not zaprinast, decreased systemic arterial pressure when injected into the perfused lobar artery in the range of doses studied. The present data demonstrate that the three phosphodiesterase inhibitors have potent, long-lasting vasodilator activity in the pulmonary vascular bed of the cat. These data suggest that there is rapid turnover of cAMP and cGMP in the pulmonary circulation and indicate that phosphodiesterase enzyme types III, IV, and V may play an important role in the regulation of vasomotor tone in the feline lung.
De Witt
B J
BJ
Department of Pharmacology SL83, Tulane University School of Medicine, 1430 Tulane Avenue, 70112, New Orleans, LA, USA.
Marrone
J R
JR
Kadowitz
P J
PJ
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002415:Cats; D004305:Dose-Response Relationship, Drug; D005260:Female; D006146:Guanidines / Q000494:pharmacology*; D008297:Male; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D011652:Pulmonary Circulation / Q000187:drug effects*; D011688:Purinones / Q000494:pharmacology*; D011724:Pyridazines / Q000494:pharmacology*; D020889:Rolipram / Q000494:pharmacology*
D006146:Guanidines; D010726:Phosphodiesterase Inhibitors; D011688:Purinones; D011724:Pyridazines; C056215:siguazodan; C011145:zaprinast; D020889:Rolipram