Worsened after 4 weeks of subcutaneous administration of Ang while blood pressure remained unaffected. In a rat remnant kidney model, blood pressure was increased by Ang- delivered subcutaneously. Proteinuria was not altered in either of the remnant kidney studies. In contrast, in a model of mesangioproliferative glomerulonephritis, anti-Thy1.1 nephritis, Ang- ameliorated the degree of glomerular scarring and decreased proteinuria. Furthermore, the reported effects of Ang- infusion on models of diabetic kidney disease have been conflicting. Benter et al. reported a decrease in blood pressure and proteinuria after 4 weeks of intraperitoneal Ang- in spontaneously hypertensive rats injected with streptozotocin, whereas Shao et al. observed worsening proteinuria and transforming growth factor beta accumulation after 6 weeks of intravenous Ang- in streptozotocin-induced diabetic rats. Differences in methodology may account for some of the discrepancy among studies, including dose of the peptide, route of administration, duration of therapy and disease model. However, it remains difficult to reconcile the findings across laboratories. Furthermore, Ang- has been reported to both attenuate and promote profibrotic pathways though mas receptor stimulation in cultured mesangial cells. Therefore, glomerular cells may exhibit variable responses to Ang- depending on the experimental conditions. Despite the vasodilatory effect of Ang- reported by others, we did not observe a reduction in systolic blood pressure in Ang–infused animals. On the contrary, animals treated with high-dose Ang- experienced an increase in blood pressure. Previous studies also found pressor effect of Ang- in rat models of kidney disease. Our radioligand Remdesivir binding curves indicate that Ang- has low affinity for the AT1 receptor. However, it is conceivable that at the administered pharmacological doses, Ang- may have elicited some degree of AT1 receptor stimulation, thereby explaining the observed rise in systolic blood pressure. However, such mechanism remains speculative. Alternatively, binding affinity might change in disease states. Others have reported that Ang- is capable of binding the AT1 receptor. We did not treat animals simultaneously with Ang- and losartan to determine if the pressor effect of Ang- could be reduced by AT1 receptor blockade. However, even under those circumstances, it would be difficult to ascertain whether the observed pressor effect of Ang- is indeed AT1 receptor-mediated because losartan alone reduced blood pressure in our animals. Because a mas receptor antagonist was not utilized, it cannot be determined whether the observed pressor effect of Ang was mas receptor-mediated.