Early blood pressure normalization independent of the class of antihypertensive agent prevents augmented renal fibronectin and albuminuria in experimental diabetic nephropathy.
OBJECTIVE
This study tested the hypothesis that prevention of the development of hypertension, and not the class of antihypertensive agent, inhibits the increase in renal fibronectin and albuminuria in experimental diabetes.


METHODS
Four-week-old spontaneously hypertensive rats (SHR), with diabetes induced by streptozotocin, were randomized for no treatment, or treatment with captopril, amlodipine, an association of captopril and amlodipine (Cap+A) or an association of captopril and verapamil (Cap+V) for 12 weeks.


RESULTS
Systolic blood pressure increased similarly in control (187 +/- 5 mm Hg, mean +/- SE) and diabetic (186 +/- 4) SHR and was kept within the normal range by amlodipine (131 +/- 3), captopril (127 +/- 3), Cap+A (134 +/- 4) and Cap+V (134 +/- 9, p < 0.0001). In diabetic rats, albuminuria was higher than in control SHR [geometric mean (variance), 1,213 (953-1,708) vs. 512 (213-850), p < 0.0001] and was reduced to a similar extent by amlodipine [573 (353-744), p < 0.0001], captopril [562 (238-771), p < 0.0001], Cap+A [679 (442-971), p < 0.0001] and Cap+V [748 (581-848) microg/24 h, p = 0.0002]. Renal fibronectin increased in diabetic rats (24.0 +/- 3.3 densitometric units, mean +/- SE) compared to control rats (9.6 +/- 1.8, p = 0.0005) and was normalized by amlodipine (9.9 +/- 1.0, p = 0.0001), captopril (11.2 +/- 0.4, p = 0.0016), Cap+A (9.9 +/- 2.0, p = 0.0004) and Cap+V (14.7 +/- 4.9, p = 0.0159).


CONCLUSIONS
In this model, tight blood pressure control rather than the class of antihypertensive agent was the main determinant factor in attenuating of nephropathy.
Lehfeld
Leandro S
LS
Division of Nephrology, Faculty of Medical Sciences, State University of Campinas (UNICAMP), Campinas, SP, Brazil.
Silveira
Lilia A
LA
Ghini
Bruno
B
Lopes de Faria
José B
JB
D000419:Albuminuria / Q000517:prevention & control*; D017311:Amlodipine / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001786:Blood Glucose / Q000032:analysis; D001794:Blood Pressure / Q000187:drug effects*; D001835:Body Weight; D002216:Captopril / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000150:complications; D003928:Diabetic Nephropathies / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*; D004357:Drug Synergism; D005353:Fibronectins / Q000037:antagonists & inhibitors*; D005919:Glomerular Filtration Rate; D006973:Hypertension / Q000517:prevention & control*; D007668:Kidney / Q000378:metabolism*; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D014700:Verapamil / Q000494:pharmacology
D000959:Antihypertensive Agents; D001786:Blood Glucose; D005353:Fibronectins; D017311:Amlodipine; D002216:Captopril; D014700:Verapamil