Sex differences in renal hemodynamics, autoregulation, and hypertensive injury in rats

Abstract

There is limited data on sex differences in renal hemodynamics and autoregulation (AR). We assessed renal vascular resistance (RVR) and renal AR in conscious male (M) and female (F) rats with intact kidneys, uninephrectomy (UNX), and UNX administered deoxycorticosterone acetate (DOCA)+salt. The susceptibility to hypertension-induced renal damage (HIRD) was also assessed in rats with UNX administered DOCA+salt. We hypothesized that M rats exhibit a lower RVR, weaker renal AR responses, and an increased susceptibility to HIRD.Sprague-Dawley rats (8-11-week-old) administered a 0.4% NaCl chow diet and water ad libitum were used. Blood pressure (BP, DSI) and renal blood flow (RBF, Transonic) were assessed in conscious rats with intact kidneys (n=12M,13F) and in rats with UNX (n=7M,8F) before and during 1 week of DOCA (3.3 mg/day s.c.) + salt (1% NaCl in drinking water). RVR was calculated as BP/RBF. Renal AR responses (fractional Δ in RBF / fractional Δ in BP) at 2.5 seconds and 20 seconds following spontaneous BP fluctuations ≥ ±5 mmHg were calculated as recently described (PMID 31792155). A 2-way ANOVA with Sidak post hoc analysis was used to assess differences among groups. Data are mean±SE, and P<0.05 was considered statistically significant.RVR was 20% (P<0.05) and 30% (P<0.05) lower in M vs. F rats with intact kidneys and UNX. DOCA+salt administration led to similar decreases in RVR (~ -20%) in both sexes (P<0.05). No sex difference in renal AR indices (~0.45) were observed at 2.5 seconds following a BP change in rats with intact kidneys, and both groups achieved complete AR compensation by 20 seconds. Renal AR indices at 2.5 seconds were slower (P<0.05) in both M and F rats with UNX (~0.75) vs. intact kidneys. Both UNX groups achieved complete renal AR compensation by 20 seconds. DOCA+salt did not impair renal AR responses in either sex.Susceptibility to HIRD was assessed in rats (n=13M,14F) with UNX administered DOCA (3.3 mg/day) + salt for 4 weeks. To produce similar BP’s, all F rats were given 1% NaCl in drinking water while different groups of M rats were given 1% NaCl (n=4), 0.5% NaCl (n=5), or 0.1% NaCl (n=4). Proteinuria and HIRD (combination of glomerular, tubulointerstitial, and vascular injury) were assessed. There were no significant differences in systolic BP between M and F rats at baseline (124±2 vs. 130±2 mmHg) or during DOCA+salt administration (173±4 vs. 166±4 mmHg). M had a greater proteinuria at 4 weeks post DOCA+salt (152±30 vs. 70±13 mg/day, P<0.01), a greater HIRD score (9±3 vs. 2±1, P<0.05), and slope of relationship between HIRD and systolic BP (0.5±0.2 vs. 0.1±0.03 HIRD/mmHg, P<0.05) as compared to F rats.These data indicate that M rats exhibit an increased susceptibility to renal injury for any given level of BP in this model of hypertension. While no sex differences in renal AR were observed, the relatively dilated renal vascular bed in M may contribute to sex differences in susceptiblity to HIRD. NIH (HL154067) and East Tennessee State University This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.