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 tubulointersti tial nephropathy seen in the obstructed kidney (OK) of 72 hours duration th rough a further increase in the activity of endogenous angiotensin II in th e OK. Also, it is known that the vasoconstrictors angiotensin II and endoth elin (ET)-1 may be implicated in the deterioration of glomerular hemodynami cs 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 immunohi stochemistry, the expression of preproET-1 mRNA and ET-1 was examined in gl omeruli of the contralateral, non-obstructed control kidney (CLK) and the O K 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 i n 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 incr eased in the OK of the Zn-deficient diet group relative to the OK of the st andard 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. Admini stration 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 di et groups. Enalapril produced no effects on the expression of prepro-ET-1 m RNA 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 biol ogical action of endogenous angiotensin II in the OK. Moreover, Zn deficien cy 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 a ngiotensin II in the OK. Zn deficiency appears to be a factor to worsen glo merular hemodynamics in the OK of the UUO setting of 72 hours duration thro ugh an increment in the biological action of the vasoconstrictors angiotens in II and ET-1.