Age-Related Differences in Vascular Effects of Pentoxifylline in Isolated Perfused Ferret Lungs

Abstract

We have determined the magnitude and sites of action of pentoxifylline (PTX), a methylxanthine derivative, in the adult and 3- to 4-week old ferret pulmonary circulation. Lungs of 8 ferrets, four 3- to 4-week-old and 4 adult, were isolated and perfused with blood. During perfusion, blood flow was kept constant, as were airway and left atrial pressures (6 and 8 cm H(2)O respectively, zone 3 conditions). In all lungs, pulmonary artery pressure was measured continuously and the circulation was partitioned into arteries, microvessels and veins, by measurement of pressures in 20-50 μm diameter subpleural arterioles and venules using the micropipette-servonulling method. Pressures were obtained in each lung during baseline, after vasoconstriction with hypoxia, and again after the infusion of PTX, 20 mg/kg, during hypoxia. We found that with hypoxia, total vascular resistance increased by ~90% in both adult and neonatal lungs; arterial and venous resistances increased by 100-180% in both age groups, with little change in microvascular resistance. PTX resulted in a significant decrease in total vascular resistance, due to a decrease in resistance in both arteries and veins. The decrease in resistance with PTX was greater in adult lungs (of the increase in resistance induced by hypoxia, 80% was eliminated by PTX) than in 3- to 4-week-old lungs (51 % elimination of tone induced by hypoxia). This difference was mainly due to a smaller reduction in arterial resistance with PTX in 3- to 4-week-old lungs. We conclude that PTX is a powerful pulmonary vasodilator in ferrets and that its effectiveness as a vasodilator depends on the age of the animal, the older animal showing greater responsiveness.

Effects of Pentoxifylline on Olfactory Sensitivity

“…23 An agedependent effect of pentoxifylline was also found in human cerebral blood flow and in vertebrate pulmonary blood flow, indicating that age-dependent physiologic changes might be responsible for the observed agerelated effect of pentoxifylline on olfactory sensitivity. [24][25][26] All patients evaluated their sense of smell as normal or better than normal except 1 patient who indicated poor olfactory function. Although some patients demonstrated a clinically significant increase in olfactory sensitivity, no patient reported a change in olfactory function after treatment with pentoxifylline.…”

Pentoxifylline Inhibits Pulmonary Fibrosis by Regulating Cellular Senescence in Mice

“…Studies have shown that the vasorelaxant effects of PTX depended on animals’ age and fundamental vasomotor tension. That is to say, the response of animals to PTX treatment was more significant when they were older ( Kaapa et al, 1991 ; Raj et al, 1992 ). Erythrocytes isolated from young and aged rats were also different in their sensitivity to PTX treatment ( Seidler and Swislocki, 1992 ).…”