Zinc deficiency further increases the enhanced expression of endothelin-1 in glomeruli of the obstructed kidney.
BACKGROUND
Zinc (Zn) is an essential trace element in humans and animals. We have recently documented that Zn deficiency may aggravate tubulointerstitial nephropathy seen in the obstructed kidney (OK) of 72 hours duration through a further increase in the activity of endogenous angiotensin II in the OK. Also, it is known that the vasoconstrictors angiotensin II and endothelin (ET)-1 may be implicated in the deterioration of glomerular hemodynamics caused in the OK. We therefore designed the present study to examine the effect of Zn deficiency on the expression of ET-1 and a potential role of endogenous angiotensin II in the expression of ET-1 in glomeruli of the OK of 72 hours duration.


METHODS
Using reverse transcription-polymerase chain reaction and immunohistochemistry, the expression of prepro-ET-1 mRNA and ET-1 was examined in glomeruli of the contralateral, non-obstructed control kidney (CLK) and the OK from rats with unilateral ureteral obstruction (UUO) of 72 hours duration fed a standard or a Zn-deficient diet for approximately 50 days. The rats in each group were treated with saline alone or the angiotensin-converting enzyme inhibitor enalapril before and after ureteral obstruction.


RESULTS
The expression of prepro-ET-1 mRNA and ET-1 was markedly greater in the OK than in the CLK in the standard and the Zn-deficient diet groups. However, the expression of prepro-ET-1 mRNA and ET-1 was substantially increased in the OK of the Zn-deficient diet group relative to the OK of the standard diet group. There were no significant differences in the expression of prepro-ET-1 mRNA and ET-1 between the CLK of the two diet groups. Administration of enalapril restored the expression of prepro-ET-1 mRNA and ET-1 in the OK to levels seen in the CLK in the standard and the Zn-deficient diet groups. Enalapril produced no effects on the expression of prepro-ET-1 mRNA and ET-1 in the CLK of the two diet groups.


CONCLUSIONS
UUO of 72 hours duration may increase the expression of prepro-ET-1 mRNA and ET-1 in glomeruli of the OK through an increment in the biological action of endogenous angiotensin II in the OK. Moreover, Zn deficiency may enhance the expression of prepro-ET-1 mRNA and ET-1 in glomeruli of the OK through a further increment in the biological action of endogenous angiotensin II in the OK. Zn deficiency appears to be a factor to worsen glomerular hemodynamics in the OK of the UUO setting of 72 hours duration through an increment in the biological action of the vasoconstrictors angiotensin II and ET-1.
Department of Hygiene & Preventive Medicine, Faculty of Medicine, Saitama Medical School, Japan. hiro@ns2.saitama-med.ac.jp
H
H
Yanagisawa
K
K
Moridaira
O
O
Wada
D000804:Angiotensin II / Q000378:metabolism; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D015415:Biomarkers; D003300:Copper / Q000032:analysis; D004656:Enalapril / Q000494:pharmacology; D019332:Endothelin-1 / Q000032:analysis / Q000235:genetics*; D016232:Endothelins / Q000235:genetics; D005260:Female; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007678:Kidney Glomerulus / Q000737:chemistry / Q000201:enzymology*; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D011498:Protein Precursors / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012083:Renin / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012871:Skin Diseases / Q000378:metabolism / Q000503:physiopathology; D014517:Ureteral Obstruction / Q000378:metabolism* / Q000503:physiopathology; D015032:Zinc / Q000172:deficiency*
D000806:Angiotensin-Converting Enzyme Inhibitors; D015415:Biomarkers; D019332:Endothelin-1; D016232:Endothelins; D011498:Protein Precursors; D012333:RNA, Messenger; D000804:Angiotensin II; D004656:Enalapril; D003300:Copper; D007703:Peptidyl-Dipeptidase A; D012083:Renin; D015032:Zinc