Pancreatic islet transplantation, but not intensive insulin therapy, corrects the pulmonary vascular complications of streptozotocin diabetes

We examined the effects of long-term streptozotocin (STZ) diabetes and its treatment by intensive insulin therapy (IIT) or pancreatic islet transplantation on pulmonary presser and depressor responses and segmental resistance profiles in female Wistar-Furth rats. Pulmonary vascular reactivity was examined using isolated, salt-perfused lungs at a constant flow rate of 30 mL min(-1) kg(-1) body weight. Baseline perfusion pressure was significantly (p < 0.05) lower in lungs obtained from IIT animals compared with all other treatment groups. Following STZ administration, presser responsiveness to 1.0 mu g of U-46619 (9,11-dideoxy-9 alpha,11 alpha-methanoepoxy prostaglandin F-2 alpha) was decreased in diabetic compared with IIT animals (9.33 +/- 0.54 vs. 11.94 +/- 0.29 mmHg (1 mmHg = 133.3 Pa)). Diabetes caused a similar decrease in the vasodilatory response to arginine vasopressin when compared with IIT animals (39.25 +/- 7.54 vs. 68.24 +/- 4.75%). Diabetes was also associated with a shift in the primary site of resistance from the pulmonary arterial to the pulmonary venous bed. This shift was restored to normal following pancreatic islet transplantation, but not IIT. IIT was also associated with significant alterations in the pattern of constrictor and dilator responses to U-46619 and arginine vasopressin. Pulmonary venous vasoconstrictor responses to U-46619 were augmented when compared with either control or diabetic animals, but not transplant. In addition, pulmonary venous vasoconstrictor responses in IIT animals were significantly greater than pulmonary arterial responses in the same group, a finding that was unique to IIT animals. Finally, IIT significantly augmented the pulmonary venous vasodilatory response to arginine vasopressin when compared with all other treatment groups. These data demonstrate significant alterations in pulmonary hemodynamic status of STZ diabetic female animals and suggest that pancreatic islet transplantation may be more beneficial than intensive insulin therapy in ameliorating these changes.