Renal and metabolic disorders depend on the renin-angiotensin system in Lyon hypertensive rats associated with diabetes.
BACKGROUND
In Lyon genetically hypertensive (LH) rats with diabetes, the effects of angiotensin converting enzyme (ACE) inhibition with perindopril on the prevention of dyslipidemia and proteinuria were evaluated by comparison with a nonspecific antihypertensive treatment.


METHODS
Diabetes was induced in 2-day-old male LH rats by intraperitoneal injection of streptozotocin (75 mg/kg). Glucose tolerance (glucose 2 g/kg by gavage), blood pressure (BP), plasma lipids, and urinary protein excretion were studied in: (i) untreated diabetic LH rats, (ii) diabetic LH rats treated from 8 to 16 weeks of age with oral perindopril at a low dose (0.01 mg/kg/day), (iii) similar rats treated with oral perindopril for the same duration at a high dose (1 mg/kg/day), and (iv) similar rats treated for the same duration with a triple therapy regimen consisting of hydralazine, hydrochlorothiazide, and reserpine (75, 15, and 0.75 mg/kg/day, respectively).


RESULTS
The neonatal administration of streptozotocin in LH rats increased nonfasting glycemia and induced a marked glucose intolerance which was accompanied by further increases in BP, plasma cholesterol, and urinary protein excretion. None of the treatments was able to modify glucose tolerance in diabetic LH rats. The low dose of perindopril was ineffective in the prevention of hypertension, dyslipidemia, and proteinuria in diabetic LH rats, while the high dose of perindopril normalized the BP, reduced the plasma lipids, and lowered the proteinuria. However, in spite of significant reduction in BP, the triple therapy failed to improve dyslipidemia and proteinuria; on the contrary, the therapy worsened these two conditions.


CONCLUSIONS
In diabetic LH rats, only ACE inhibition is of benefit to the kidney and lipidemia, thereby demonstrating that antihypertensive regimens may differ in their capacity to protect the target organs and lipid metabolism in a diabetic setting.
Emonnot
Léa
L
Centre National de la Recherche Scientifique FRE 3075, Interactions Neurovasculaires, Université de Lyon 1, Université de Lyon, Lyon, France.
Cohen
Richard
R
Lo
Ming
M
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000150:complications*; D006949:Hyperlipidemias / Q000517:prevention & control*; D006973:Hypertension / Q000150:complications*; D007674:Kidney Diseases / Q000517:prevention & control*; D008297:Male; D020913:Perindopril / Q000494:pharmacology; D011507:Proteinuria / Q000517:prevention & control; D051381:Rats; D012084:Renin-Angiotensin System / Q000502:physiology*
D000806:Angiotensin-Converting Enzyme Inhibitors; D020913:Perindopril