title: Comparison of effects of ACE inhibition with calcium channel blockade on renal disease in a model combining genetic hypertension and diabetes.
abstract: The aim of this study was to compare the renal effects of angiotensin converting enzyme (ACE) inhibition with calcium channel blockade in a model combining genetic hypertension with diabetes. Streptozotocin diabetes was induced in spontaneously hypertensive rats (SHR). The animals were then randomized to receive no treatment, the ACE inhibitor, perindopril, or the dihydropyridine calcium antagonist lacidipine. Body weight, systolic blood pressure, glycemic control, renal function, and albumin excretion rate (AER) were assessed serially over the 32-week study period. At week 32 the animals were killed and glomerular volume was measured. Both antihypertensive regimens significantly reduced systolic blood pressure in diabetic SHR. There was no significant difference in glycemic control, serum creatinine, or glomerular filtration rate among the three groups at week 32. The ACE inhibitor perindopril significantly reduced AER and glomerular hypertrophy over the 32 weeks, whereas the calcium antagonist lacidipine failed to reduce AER or glomerular hypertrophy. Thus, in contrast to the effects of ACE inhibition, calcium channel blockade with lacidipine, despite significantly reducing blood pressure, failed to reduce renal injury in this model. These results support the hypothesis that antihypertensive regimens may differ in their capacity to protect the diabetic kidney, despite similar effects on systemic blood pressure.
authors.affiliation: Department of Medicine, University of Melbourne, Heidelberg Repatriation/Austin Hospitals, Australia.
authors.forename: J R
authors.initials: JR
authors.lastname: Rumble
authors.forename: A E
authors.initials: AE
authors.lastname: Doyle
authors.forename: M E
authors.initials: ME
authors.lastname: Cooper
mesh_terms: D000419:Albuminuria / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D004095:Dihydropyridines / Q000494:pharmacology*; D004195:Disease Models, Animal; D006973:Hypertension / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D007211:Indoles / Q000494:pharmacology*; D007674:Kidney Diseases / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D008297:Male; D020913:Perindopril; D011897:Random Allocation; D051381:Rats; D011918:Rats, Inbred SHR; D012083:Renin / Q000097:blood / Q000187:drug effects
chemical_list: D001786:Blood Glucose; D004095:Dihydropyridines; D007211:Indoles; C060285:lacidipine; D012083:Renin; D020913:Perindopril