Differential Pulmonary Vascular Effects of Streptozotocin Diabetes in Male and Female Rats

Abstract

We examined the effect of streptozotocin (STZ) diabetes on pulmonary pressor responses and segmental pulmonary vascular resistance in male and female Wistar-Furth rats. Pulmonary vascular reactivity was studied using isolated, salt-perfused lungs at a constant flow rate of 30 ml/min/kg body weight. Following STZ administration, pressor responsiveness to 1.0 μg of U-46619 (9,11 dideoxy-9α, 11α-methanoepoxy Prostaglandin F_2α was diminished (p < 0.05) in lungs obtained from male diabetic rats when compared to sham treated controls (7.87 ± 1.67 vs. 13.59 ± 1.67 mmHg). In contrast, diabetes failed to affect pressor responsiveness in lungs from female animals. In another set of animals, segmental pulmonary vascular resistance was determined in lungs isolated from male and female diabetic or sham-treated (STZ carrier vehicle) animals. Total pulmonary vascular resistance was significantly elevated in male diabetic animals as compared to controls. This elevation was attributable to significant increases in resistance at the level of small pulmonary veins. In addition, diabetes was associated with a shift in the primary site of resistance from small arteries to small veins in male animals. We were unable to detect any effect of short-term diabetes on the segmental resistance profile in lungs obtained from female animals. These data indicate that both the pulmonary segmental resistance profile and pulmonary vascular reactivity are altered by short-term diabetes in male rats. Additionally, these studies demonstrate gender-related effects of short-term diabetes, which may suggest a more favorable pulmonary response to diabetes in female animals.