Abstract P420: Sexual Difference of Tubular Renin Angiotensin System (RAS) in 2 Kidney 1 Clip Rats

Abstract

Background: Premenopausal female manifests lower blood pressure compared with age-matched male. Intrarenal RAS is thought to be an important role in hypertension and hypertensive renal disease, while there is rare information about sexual difference in intrarenal RAS. This study was performed to evaluate sexual difference of tubular RAS in 2 kidney 1 clip(2K1C) rat model. Methods: A 2.5-mm clip was inserted into the left renal artery of male and female Spargue-Dawley rats and they were euthanized at 5 week following the operation. Systolic blood pressure(SBP) was measured via the tail-cuff method at 10 day interval. Medullary area for tubular RAS and cardiac tissue was collected for analysis of local RAS expression. Results: At 30 days after clipping operation, SBP and albuminuria was significantly increased in 2K1C male rats (SBP: male 176.75±5.58 vs. female 106.71±8.68 mmHg, p 0.004, albumin/Cr ratio: male 116.93±33.96 vs. female 56.40±13.94 mg/g, p 0.029). Also, left ventricular hypertrophy was observed only in male rats, however cardiac ACE2 and MasR mRNA did not show sexual difference. The clipped kidney(CK) of 2K1C male rat presented worse glomerulosclerosis and more macrophage infiltration. Renin mRNA was more expressed in female CK, but protein expression was rather decreased in female CK and non-clipped kidney(NCK). 2K1C female rats exhibited highly augmented ACE2 and Mas receptor(MasR) in mRNA and protein, but ACE was augmented in mRNA and reduced in protein. Immunohistochemistry showed that tubular renin and ACE was increased in 2K1C male rats, in contrast ACE2 and MasR were increased in 2K1C female rats. Medullary angiotensin II(AngII) was significantly lower in male CK, but angiotensin 1-7(Ang1-7) was higher in female CK but did not show significance (CK AngII: male 201.88±10.40 vs. female 137.01±19.33 fg/mg p 0.030, CK Ang1-7: male 22.21±4.51 vs. female 57.93±19.59 fg/mg p 0.190). Conclusions: Same insult of renal artery stenosis aroused different clinical outcome in 2K1C male and female. Differently activated tubular RAS might influence difference in clinical manifestation. Superiority of nonclassic tubular RAS in female rats could limit the adverse effect of classic RAS under renovascular hypertension.