Comparison of vasodilator effects of DN-9693, a selective inhibitor of cyclic AMP phosphodiesterase, and isobutylmethylxanthine, a non-selective one, in dogs.
The present experiments were performed in anesthetized dogs in order to determine if DN-9693, a new antiplatelet agent known to selectively inhibit cyclic AMP phosphodiesterase (PDE), and isobutylmethylxanthine (IBMX), which inhibits both cyclic AMP and GMP PDEs, have different cardiovascular actions. With intra-arterial administration into the left anterior descending coronary, femoral, cranial mesenteric and renal arterial beds perfused at constant pressure with autologous blood, both agents increased blood flow in a similar dose range. DN-9693 was longer-acting than IBMX. Both agents were nearly equi-effective in the femoral circulation, but DN-9693 was 1.5-2 times less effective than IBMX in the others. With intravenous administration, both agents were equi-effective in increasing the maximum rate of rise of left ventricular pressure heart rate and myocardial oxygen consumption and in reducing mean blood pressure. However, DN-9693 was less effective in increasing coronary sinus outflow than IBMX. These results suggest the following: 1) Vasodilation in the somatic rather than the visceral circulation is important in reducing mean blood pressure. 2) Cyclic GMP may not be involved in the cardiac action of PDE-inhibitors. 3) Cyclic GMP may be involved in the vasodilator effect of PDE-inhibitors in the coronary, mesenteric and renal circulations but least involved in the femoral circulation.
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology*; D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D003326:Coronary Circulation / Q000187:drug effects; D004285:Dogs; D005260:Female; D005269:Femur / Q000098:blood supply; D008297:Male; D009206:Myocardium / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D011799:Quinazolines / Q000494:pharmacology*; D012039:Regional Blood Flow / Q000187:drug effects; D012079:Renal Circulation / Q000187:drug effects; D013152:Splanchnic Circulation / Q000187:drug effects; D013806:Theophylline / Q000031:analogs & derivatives*; D014665:Vasodilator Agents
D000970:Antineoplastic Agents; D011799:Quinazolines; D014665:Vasodilator Agents; C049662:1,5-dihydro-7-(1-piperidinyl)-imidazo(2,1-b)quinazolin-2(3H)-one; D013806:Theophylline; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D015056:1-Methyl-3-isobutylxanthine