Effect of angiotensin II blockade on renal injury in mineralocorticoid-salt hypertension.
Kidney function and structure were compared in control rats (group 1) and in 3 groups of rats made hypertensive by administration of aldosterone and saline for 8 weeks (groups 2, 3, and 4). Group 2 rats received only aldosterone and saline, while group 3 also received losartan and group 4 also received enalapril. Rats in all groups were subjected to uninephrectomy before beginning the experiment. Hypertension and proteinuria in rats given aldosterone and saline were not affected by losartan or enalapril (8-week values for blood pressure in mm Hg: 135+/-3 group 1, 193+/-4 group 2, 189+/-4 group 3, 189+/-5 group 4; P<0.05 groups 2, 3, and 4 versus 1; 8-week values for proteinuria in mg/d: 44+/-8 group 1, 278+/-34 group 2, 267+/-37 group 3, 289+/-36 group 4; P<0.05 groups 2, 3, and 4 versus 1). Vascular, glomerular, and tubulointerstitial injury accompanied hypertension and proteinuria at 8 weeks. Losartan and enalapril did not prevent vascular injury, which was characterized by thickening of arterial and arteriolar walls and by fibrinoid necrosis and thrombotic microangiopathy. Likewise, losartan and enalapril did not reduce the prevalence of glomerular segmental sclerosis (1+/-1% group 1, 10+/-2% group 2, 11+/-2% group 3, 13+/-2% group 4; P<0.05 groups 2, 3, and 4 versus 1) or limit tubulointerstitial injury as reflected by the volume fraction of the cortical interstitium (15+/-1% group 1, 20+/-1% group 2, 21+/-1% group 3, 21+/-1% group 4; P<0.05 groups 2, 3, and 4 versus 1). These findings suggest that local angiotensin II activity does not contribute to the development of renal injury in mineralocorticoid-salt hypertension.
Sorooshian
M
M
Division of Nephrology, VA Palo Alto Health Care System and Stanford University, Palo Alto, California, USA.
Olson
J L
JL
Meyer
T W
TW
D000284:Administration, Oral; D000450:Aldosterone; D000804:Angiotensin II / Q000037:antagonists & inhibitors*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D004195:Disease Models, Animal; D004656:Enalapril / Q000008:administration & dosage*; D006977:Hypertension, Renal / Q000139:chemically induced / Q000188:drug therapy*; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D007677:Kidney Function Tests; D019808:Losartan / Q000008:administration & dosage*; D008297:Male; D009392:Nephrectomy; D011507:Proteinuria / Q000139:chemically induced; D051381:Rats; D017208:Rats, Wistar; D051437:Renal Insufficiency / Q000139:chemically induced / Q000188:drug therapy*; D012965:Sodium Chloride
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D000804:Angiotensin II; D012965:Sodium Chloride; D000450:Aldosterone; D004656:Enalapril; D019808:Losartan