Cardiac hypertrophy in diabetic spontaneously hypertensive rats: role of angiotensin II?
1. In the present study the role of angiotensin II (AngII) in the development of cardiac hypertrophy in diabetes combined with hypertension was investigated. 2. Diabetes was induced in 8-week-old male spontaneously hypertensive rats (SHR) by intravenous injection of streptozotocin (45 mg/kg bodyweight). Diabetic SHR were treated with the angiotensin-converting enzyme (ACE) inhibitor ramipril at a dose of 0.4 mg/kg per day. 3. Twelve weeks following the onset of diabetes, hearts were arrested in diastole and were perfusion-fixed. The right ventricle and left ventricle plus septum were weighted and the volume of the ventricular walls was determined using the Cavalieri principle. 4. Induction of diabetes in SHR led to a significant reduction in bodyweight compared with non-diabetic control SHR and this was not affected by ramipril treatment. The development of hypertension was not as great in diabetic SHR compared with controls, such that at 12 weeks following the onset of diabetes systolic blood pressure (SBP) averaged 191 +/- 3 and 230 +/- 4 mmHg in diabetic SHR and controls, respectively. Ramipril treatment significantly lowered SBP in diabetic SHR. 5. The left ventricle plus septum volume:bodyweight ratio (LV vol:BW) was significantly higher in diabetic SHR compared with controls (3.83 +/- 0.19 and 3.26 +/- 0.16 mm3/g, respectively). Ramipril treatment did not affect growth of the left ventricle in diabetic SHR with the LV vol:BW ratio averaging 3.95 +/- 0.14 mm3/g. Similar trends on growth were observed in the right ventricle. 6. In conclusion, the development of cardiac hypertrophy in diabetic SHR appears to occur by mechanisms independent of AngII and the elevation of blood pressure.
Black
M J
MJ
Department of Medicine, University of Melbourne, Austin & Repatriation Medical Centre, Heidelberg, Victoria, Australia.
Briscoe
T
T
Bertram
J F
JF
Jackson
B
B
Johnston
C I
CI
D000804:Angiotensin II / Q000502:physiology*; D000818:Animals; D001794:Blood Pressure; D001835:Body Weight; D002306:Cardiac Volume; D006332:Cardiomegaly / Q000503:physiopathology*; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000503:physiopathology*; D006346:Heart Septum / Q000503:physiopathology; D006973:Hypertension / Q000503:physiopathology*; D017379:Hypertrophy, Left Ventricular / Q000503:physiopathology; D008297:Male; D009929:Organ Size; D051381:Rats; D011918:Rats, Inbred SHR
D000804:Angiotensin II