Increased bradykinin and "normal" angiotensin peptide levels in diabetic Sprague-Dawley and transgenic (mRen-2)27 rats

Background. The transgenic (mRen-2)27 rat (TGR) is a high tissue renin, hig h angiotensin (Ang) II model of hypertension. When administered streptozoto cin (STZ), TGRs develop a rapidly progressive diabetic nephropathy with ren al failure over 12 weeks. Bradykinin (BK) and Ang II are potent vasoactive peptides that may participate in the vascular and metabolic abnormalities o f diabetes. Methods. TGR and Sprague-Dawley (SD) rats were administered STZ (diabetic) or citrate buffer (nondiabetic) at six weeks of age. Diabetic rats received daily ultralente insulin to maintain moderate hyperglycemia (similar to 18 mM). Rats were sacrificed four- and eight-weeks post-STZ or vehicle. Results. Diabetes did not modify the blood pressure of either SD rats or TG Rs. Diabetes increased levels of BK-(1-9) and its metabolite BR-(1-7) in ki dney, aorta, and heart of both SD rats and TGRs. Diabetes did not influence Ang II levels in plasma, kidney, aorta, heart, or adrenal gland of SD rats , but reduced to normal the elevated Ang II levels in plasma, kidney, aorta , and adrenal gland of TGRs. Conclusions. STZ-induced diabetes was associated with elevated tissue level s of BK-(1-9) and "normal" circulating and tissue levels of Ang II. The inc reased BK-(1-9) levels were consistent with the participation of this pepti de in the vascular and metabolic abnormalities of diabetes. However, the ra pidly progressive nephropathy of diabetic TGRs was not associated with BK-( 1-9) and Ang II levels in target organs that differed from those of diabeti c SD rats.