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, high angiotensin (Ang) II model of hypertension. When administered streptozotocin (STZ), TGRs develop a rapidly progressive diabetic nephropathy with renal failure over 12 weeks. Bradykinin (BK) and Ang II are potent vasoactive peptides that may participate in the vascular and metabolic abnormalities of 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 ( approximately 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 TGRs. Diabetes increased levels of BK-(1-9) and its metabolite BK-(1-7) in kidney, 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 levels of BK-(1-9) and "normal" circulating and tissue levels of Ang II. The increased BK-(1-9) levels were consistent with the participation of this peptide in the vascular and metabolic abnormalities of diabetes. However, the rapidly progressive nephropathy of diabetic TGRs was not associated with BK-(1-9) and Ang II levels in target organs that differed from those of diabetic SD rats.
Campbell
D J
DJ
St. Vincent's Institute of Medical Research, Fitzroy, Victoria, Australia. J.Campbell@medicine.unimelb.edu.au
Kelly
D J
DJ
Wilkinson-Berka
J L
JL
Cooper
M E
ME
Skinner
S L
SL
D000804:Angiotensin II / Q000097:blood / Q000378:metabolism*; D000818:Animals; D030801:Animals, Genetically Modified; D001786:Blood Glucose / Q000032:analysis; D001835:Body Weight / Q000502:physiology; D001920:Bradykinin / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D004798:Enzymes / Q000097:blood; D005260:Female; D006728:Hormones / Q000097:blood; D006973:Hypertension / Q000097:blood / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D007668:Kidney / Q000473:pathology; D051379:Mice; D009929:Organ Size / Q000502:physiology; D010446:Peptide Fragments / Q000097:blood / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D012083:Renin / Q000235:genetics / Q000502:physiology*
D001786:Blood Glucose; D004798:Enzymes; D006728:Hormones; D010446:Peptide Fragments; D000804:Angiotensin II; D012083:Renin; D001920:Bradykinin