Apoptosis of circulating lymphocyte in rats with unilateral ureteral obstruction: role of angiotensin II.
BACKGROUND
Unilateral ureteral obstruction (UUO) could induce increased renal angiotensin II (ANG II), which enhances apoptosis of renal tubular cells and renal tissue loss. Systemic ANG II is also increased in UUO. There are no data available about whether UUO can induce apoptosis of circulating lymphocytes or not.


METHODS
UUO or sham-operated male Wistar rats (n = 8 in each group) were fed a drinking solution containing water, angiotensin II receptor type 1 antagonist (ARA; losartan, 500 mg/L) or angiotensin-converting enzyme inhibitor (ACEI; enalapril: 200 mg/L) for 1 day or 7 days. Blood samples were collected and circulating lymphocyte cells were separated. The apoptotic cells were detected by in situ terminal deoxynucleotidyl transferase (TdT assay)-mediated digoxigenin/antidigoxigenin conjugated fluorescein method and counted under a fluorescence microscope. The apoptotic index was calculated.


RESULTS
UUO caused marked increases in the apoptotic index of circulating lymphocytes in UUO rats at both 1 day and 7 days when compared with the respective sham groups (P < 0.001). Neither ARA nor ACEI treatment had an effect on the apoptotic index values in the UUO rats at 1 day. In the UUO rats at 7 days, the apoptosis of circulating lymphocytes was markedly decreased from 29.2 +/- 2.7% to 11.9 +/- 2.7% (P < 0.01) in the ARA-treated rats and to 7.6 +/- 2.7% (P < 0.001) in the ACEI-treated rats.


CONCLUSIONS
UUO, via stimulation of ANG II, could promptly enhance apoptosis of circulating lymphocytes. The apoptosis persisted throughout the 7 days of the study. Prolonged UUO would impair lymphocyte cell immunity and the host defense mechanism. Continuous treatment with either ARA or ACEI could abrogate ANG II-stimulated circulating lymphocyte apoptosis.
Eiam-Ong
Somchit
S
Department of Physiology, Faculty of Medicine, Chulalongkorn University Hospital, Bangkok, Thailand.
Udom
Janpen
J
Sueblinvong
Tada
T
Eiam-Ong
Somchai
S
D000804:Angiotensin II / Q000097:blood*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology*; D004656:Enalapril / Q000494:pharmacology; D007958:Leukocyte Count; D019808:Losartan / Q000494:pharmacology; D008214:Lymphocytes / Q000166:cytology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D014517:Ureteral Obstruction / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology*
D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D000804:Angiotensin II; D004656:Enalapril; D019808:Losartan