EFFECT OF CHRONIC INFUSION OF CORTISOL ON RENIN GENE-EXPRESSION AND RENIN RESPONSE TO HEMORRHAGE IN FETAL LAMBS

In the ovine fetus, plasma renin levels increase close to term, and renin responses to various stimuli are enhanced when compared with responses earlier in gestation. These changes are accompanied by increases in renal renin gene expression and renin content, and they occur in conjunction with elevations in fetal plasma cortisol. Thus, the purpose of this study was to test the hypothesis that a chronic, physiologic elevation in fetal plasma cortisol in early gestation would increase activity in the renin-angiotensin system prematurely. We studied fetuses (control, n = 8; cortisol infused, n = 11) at 94 +/- 2 d of gestation. Fetal vessels were catheterized, and cortisol or saline solution was infused for 6 d. At the end of infusion, fetuses were hemorrhaged approximately 30% of estimated blood volume. Blood samples were collected to measure plasma renin concentration. Then the animals were killed, and kidneys were removed to measure renin mRNA and renin content. Plasma cortisol concentrations in the control and cortisol-treated animals were 7.2 +/- 0.8 and 57.7 +/- 8.6 nmol/L (p < 0.01), respectively. Basal plasma renin concentrations were similar in the two groups 3.2 +/- 0.4 versus 4.4 +/- 1.8 ng of angiotensin I/mL/h, and there was a significant increase after hemorrhage in the cortisol-treated group only. Renal renin content and mRNA levels were similar in the two groups. These data indicate that chronic increases in cortisol in fetal lambs at 0.65 gestation significantly enhance the renin response to hemorrhage but do not alter renal renin gene expression.