Cardiovascular deterioration in STZ-diabetic rats: possible role of vascular RAS.
The precise mechanisms involved in the etiology of cardiovascular complications in diabetes are undefined. Recent evidence suggests that the renin-angiotensin system plays a predominant role in the genesis of these complications. The temporal evolution of vascular angiotensin-converting enzyme (ACE) activity was evaluated in streptozotocin-diabetic rats 2 and 4 weeks following the induction of diabetes. Vascular ACE activity was correlated with acetylcholine-induced relaxation, systolic blood pressure, and cardiac output index, establishing a possible link between these variables. Age-matched Sprague-Dawley rats were used as controls. ACE activity in aortic homogenates doubled in rats after 2 weeks of diabetes as compared with controls (0.46 +/- 0.06 vs. 0.19 +/- 0.02 nmol/mg x min, n = 8, p < 0.05). In contrast, no difference was observed between rats 4 weeks following diabetes onset (0.20 +/- 0.05 nmol/mg x min) and controls (n = 8, p > 0.05). Impaired endothelial function was also observed in the aorta of diabetic animals. The maximal aortic relaxation with 10 micromol/l acetylcholine was reduced by 40% in diabetic rats 2 weeks after onset and by 41% after 4 weeks when compared to controls (n = 8, p < 0.05). Two weeks following diabetes induction, the cardiac output index decreased by 16% and after 4 weeks by 30% (n = 4, p < 0.05). Systolic blood pressure increased from 116 +/- 12 mm Hg before diabetes to 158 +/- 4 mm Hg (p < 0.05) after 2 weeks and to 182 +/- 5 mm Hg after 4 weeks (p < 0.05). Together, these results suggest that a local renin-angiotensin system plays an important role in the genesis of vascular dysfunction and cardiac deterioration within the first stages of diabetes. A high vascular ACE activity may promote progressive deterioration of the cardiovascular system in streptozotocin-diabetic rats from the earliest stages by increasing peripheral resistance, blood pressure, preload, afterload, and cardiac work.
Crespo
María J
MJ
Department of Physiology, University of Puerto Rico School of Medicine, San Juan, P.R., USA. mcrespo@rcm.upr.edu
Moreta
Sovietsky
S
González
Juan
J
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001012:Aorta, Abdominal / Q000201:enzymology / Q000503:physiopathology; D001794:Blood Pressure; D002302:Cardiac Output; D002319:Cardiovascular System / Q000503:physiopathology*; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000201:enzymology / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000503:physiopathology; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000201:enzymology / Q000503:physiopathology; D007703:Peptidyl-Dipeptidase A / Q000097:blood / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012084:Renin-Angiotensin System; D014665:Vasodilator Agents / Q000494:pharmacology
D014665:Vasodilator Agents; D007703:Peptidyl-Dipeptidase A; D000109:Acetylcholine