Temporary treatment of prepubescent rats with angiotensin inhibitors suppresses the development of hypertensive nephrosclerosis.
Hypertensive nephrosclerosis is a leading cause of end-stage renal disease; therefore, strategies to prevent the development of renal disease require close study. Here it is demonstrated that transient treatment of prepubescent rats with angiotensin inhibitors attenuated their susceptibility to the development of hypertensive nephrosclerosis after maturation. Stroke-prone spontaneously hypertensive Izumo strain rats were divided into four groups, treated with vehicle, the angiotensin-converting enzyme inhibitor (ACEI) delapril (40 mg/kg per d), the angiotensin receptor antagonist (AT1R-Ant) candesartan cilexetil (1 mg/kg per d), or the vasodilator hydralazine (25 mg/kg per d) from weaning to puberty (3 to 10 wk of age), and then monitored without treatment for 6 mo. BP in the ACEI- and AT1R-Ant-treated groups remained significantly decreased, compared with the untreated and hydralazine-treated groups. Moreover, marked proteinuria and nephrosclerosis developed in the untreated and hydralazine-treated groups at 30 wk but were suppressed in the ACEI- and AT1R-Ant-treated groups. Of interest, plasma renin activity, plasma angiotensin II concentrations, and renal renin mRNA levels were reduced by >50% in the ACEI- and AT1R-Ant-treated rats, suggesting that the treatments may have attenuated the development of nephrosclerosis by overcoming the susceptibility of stroke-prone spontaneously hypertensive rats to overactivation of the renin-angiotensin system.
Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.
Hideaki
H
Nakaya
Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.
Hiroyuki
H
Sasamura
Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.
Matsuhiko
M
Hayashi
Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.
Takao
T
Saruta
D000804:Angiotensin II / Q000097:blood; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D000809:Angiotensins / Q000037:antagonists & inhibitors*; D000818:Animals; D001562:Benzimidazoles / Q000627:therapeutic use*; D001713:Biphenyl Compounds / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D006332:Cardiomegaly / Q000473:pathology; D015870:Gene Expression / Q000187:drug effects; D020022:Genetic Predisposition to Disease; D006830:Hydralazine / Q000627:therapeutic use; D006973:Hypertension / Q000188:drug therapy* / Q000652:urine; D007189:Indans / Q000627:therapeutic use; D007668:Kidney / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D008297:Male; D009400:Nephrosclerosis / Q000517:prevention & control*; D011507:Proteinuria / Q000652:urine; D051381:Rats; D011918:Rats, Inbred SHR / Q000235:genetics; D012083:Renin / Q000097:blood; D020521:Stroke / Q000235:genetics; D013777:Tetrazoles; D013997:Time Factors; D014665:Vasodilator Agents / Q000627:therapeutic use
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000809:Angiotensins; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D007189:Indans; D013777:Tetrazoles; D014665:Vasodilator Agents; D000804:Angiotensin II; D006830:Hydralazine; D012083:Renin; C077793:candesartan cilexetil; C047759:delapril