Alteration of segmental vascular resistance in the pulmonary circulation of diabetic rats

Numerous studies have shown that altered plasma glucose and (or) insulin have profound effects on the pulmonary circulation. Recently, we documented diminished pressor responses to the synthetic thromboxane analogue U-46619 (9,11-dideoxy-9 alpha, 11 alpha-methanoepoxy prostaglandin F2 alpha) following short-term streptozotocin-induced diabetes in rats. However, these earlier studies examined the effects of diabetes on resistance changes across the entire pulmonary vasculature and made no effort to localize the site(s) of any abnormalities. Thus, in the present study we examined segmental pulmonary vascular resistances using the double-occlusion method in isolated, perfused rat lungs 2 weeks after streptozotocin-induced diabetes. Under baseline conditions, total pulmonary vascular resistance (TPVR) did not differ in lungs isolated from control and diabetic animals (0.66 +/- 0.03 vs. 0.85 +/- 0.05 mmHg.mL-1.min-1, respectively (1 mmHg = 133.3 Pa)). However, control animals demonstrated greater arterial (Ra) than venous (Rv) contribution to TPVR (0.43 +/- 0.02 vs. 0.23 +/- 0.02 mmHg.mL-1.min-1, respectively). This relationship was reversed in diabetic animals (Ra = 0.30 +/- 0.02 mmHg.mL-1.min-1; Rv = 0.54 +/- 0.04 mmHg.mL-1.min-1). Following constriction with U-46619 this pattern persisted, although the absolute vasoconstrictor response to the agent was similar in each segment. Likewise, this pattern of resistance was unaffected following dilation of the pulmonary vascular bed with arginine vasopressin. These findings illustrate that pulmonary segmental vascular resistances are altered and, more specifically, that pulmonary venous resistance is selectively increased, 2 weeks following the induction of diabetes.