Attenuation of pulmonary and systemic vasoconstriction with pentoxifylline and aminophylline.
The effects of acute administration of therapeutic doses (1-10 mg/kg) of pentoxifylline and aminophylline on the resistance of the systemic and pulmonary circuits in anaesthetized dogs and pigs were tested. During room air breathing, neither of the two substances caused a significant change in systemic vascular resistance (SVR) or pulmonary vascular resistance (PVR). During hypoxia (10% O2 and nitrogen), however, both substances caused a significant reduction in PVR (p less than 0.05) without affecting SVR. The largest dose of pentoxifylline decreased PVR from 7.8 +/- 2.8 to 4.4 +/- 1.5 in dogs and from 9.9 +/- 1.4 to 5.8 +/- 0.6 mmHg.L-1.min in pigs. Aminophylline was equally effective and selective in lowering PVR but not SVR during hypoxia. When SVR was elevated in dogs by continuous infusion of angiotensin, pentoxifylline lowered SVR from 139 +/- 27 to 83 +/- 20 mmHg.L-1.min (p less than 0.05). The simultaneous small elevation in PVR during angiotensin infusion was also attenuated to base-line value by pentoxifylline injection. These results suggest that xanthines, in therapeutic doses, can have a profound vasodilator effect on either the systemic or on the pulmonary circuit, only wherever the vessels are constricted. The vasodilatory effect of pentoxifylline is viewed as a second beneficial effect besides the benefit derived from its action on erythrocyte deformability.
Hakim
T S
TS
Department of Physiology, McGill University, Montréal, Qué., Canada.
Petrella
J
J
D000628:Aminophylline / Q000494:pharmacology*; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D004285:Dogs; D006439:Hemodynamics / Q000187:drug effects; D000860:Hypoxia / Q000503:physiopathology; D008168:Lung / Q000098:blood supply*; D010431:Pentoxifylline / Q000494:pharmacology*; D013552:Swine; D013805:Theobromine / Q000031:analogs & derivatives*; D014655:Vascular Resistance / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects*
D000804:Angiotensin II; D000628:Aminophylline; D013805:Theobromine; D010431:Pentoxifylline