Abstract P267: Sex Differences in Cyp450 Activity and the Development of Hypertension and Renal Injury in the Dahl S Rat

Abstract

It is well documented that a sexual dimorphism exists in the regulation of blood pressure in both the human population as well as experimental animal models, however evidence of a sex difference is lacking in the Dahl S rat. Thus, we hypothesize that alterations in CYP450 expression and 20-HETE production contribute to the progression of renal injury in Dahl S rats. Consistent with what we have previously reported, no difference was noted in the blood pressure of male or female Dahl SSJr rat (213.8±12 vs 196.8±13 mmHg, ns) following 4 weeks of a high salt diet (8%NaCl). However, proteinuria (148±25 vs 355±22 mg/day, p<0.05) and renal injury (1.9±0.01 vs 2.5±0.2) were lower in female relative to male rats. In addition, GFR was significantly reduced in male vs female rats (392.4±89 vs 829.5±98 μl/min/g, p<0.05) following at high salt challenge. Renal cortical (11.3.8±16 vs 20.99±2.8 pmol/min/mg, p<0.05) and outer medullary (19.4±3 vs 6.9±1.8 pmol/min/mg, p<0.05) 20-HETE production was elevated in female versus male rats. Furthermore, renal vascular 20-HETE production was elevated in the renal vessels compared to males (0.53±0.23 vs 3.2±1.2 pmol/min/mg, p<0.05). Thus, alterations in the production of renal eicosanoids may contribute to the delay in renal injury in females relative to male Dahl SSJr rats. AHA 14SDG20160020