Early blood pressure-independent cardiac changes in diabetic rats.
Cardiac remodeling is a key event in both diabetic and hypertensive heart diseases. In the present study, we investigated early myocardial changes in an animal model, the male Sabra rat model (SBH/y) of salt-induced hypertension-rendered diabetic with streptozotocin. Control non-diabetic (C), diabetic (D), and D or C rats made hypertensive by salt loading (DS or CS) were studied after 6 weeks. M-mode echocardiography revealed that left ventricular internal dimension during diastole and systole were significantly increased in D and DS, but not in C or CS. Concurrently, we found in D and DS an increase in cardiac beta-myosin heavy chain, atrial natriuretic peptide, skeletal alpha-actin mRNA, type III collagen, and transforming growth factor-beta. Myocardial angiotensin-converting enzyme (ACE) mRNA levels were increased while ACE2 mRNA levels were decreased in both D and DS groups. Cardiac angiotensin-1 (AT1) receptor protein levels were unchanged but the levels of phosphorylated (p) ERK and Jun-NH(2)-protein kinase (JNK) were increased in D and DS. In conclusion, we detected early cardiac changes in diabetic rats that were unrelated to hypertension. The increase in ACE, the decrease in ACE2, and the increase in cardiac pERK and pJNK suggest an increase in free angiotensin II and AT1R signaling in the diabetic myocardium as a possible mechanism contributing to cardiac remodeling in diabetes.
Landau
Daniel
D
Department of Pediatrics A, Faculty of Health Sciences, Soroka University Medical Center, Ben Gurion University, PO Box 151, Beer Sheva 84101, Israel.
Chayat
Chen
C
Zucker
Nili
N
Golomb
Eli
E
Yagil
Channa
C
Yagil
Yoram
Y
Segev
Yael
Y
D000818:Animals; D017209:Apoptosis; D001786:Blood Glucose / Q000032:analysis; D001794:Blood Pressure; D001835:Body Weight; D003921:Diabetes Mellitus, Experimental / Q000473:pathology* / Q000503:physiopathology; D004452:Echocardiography; D020935:MAP Kinase Signaling System; D008297:Male; D009929:Organ Size; D051381:Rats; D012084:Renin-Angiotensin System / Q000502:physiology; D013311:Streptozocin; D024723:Ventricular Myosins / Q000235:genetics; D020257:Ventricular Remodeling
D001786:Blood Glucose; D013311:Streptozocin; D024723:Ventricular Myosins