Effect of db‐cAMP on Renal Interstitial Hydrostatic Pressure (RIHP) Response to Renal Medullary Direct Interstitial Volume Expansion (DIVE) in rats

Abstract

Renal medullary (rm) DIVE (100 μl infusion in 30 s) with either 0.9% saline solution (SS) or 2% albumin in SS rises slow, progressive and indistinctly the RIHP (FASEB J 27:1110.2,2013). Given the sui generis conformation and architecture of renal medullary interstitium, we assessed if dibutyryl‐cAMP (db‐cAMP, a collagen gel contraction inhibitor) modifies the time curse of RIHP response to rm DIVE with SS. Subcapsular RIHP was continuously measured in anesthetized rats with right nephrectomy, acute left renal denervation, hormonal clamp and control of renal perfusion pressure (100 mmHg) before (Pre: 30 min), during (30 s) and after (Post: 60 min) sham rm DIVE (time CTR group n = 9) and real rm DIVE with either SS (SS group, n = 8) or SS + 5mM db‐cAMP (db‐cAMP group, n = 8). There were no differences among groups in body weight, hematocrit nor plasma protein concentration at any time. The table below shows the absolute values of RIHP (mean ± SEM) before rm DIVE, in the last 10 s of rm DIVE and 20, 40 and 60 min after rm DIVE. 1WANOVA + Tukey test: ¨ P<0.05 vs. CTR group at any time point. 1WRMANOVA: · P<0.008 vs. Before. ANCOVA: there were effect of both RIHP before rm DIVE (as covariate) at any time point (P<0.001) and of group (P<0.02 in the last 10 s of rm DIVE and P<0.0001 60 min after rm DIVE). MANOVA of overall ΔRIHP (after RIHP − before RIHP) data showed time (P<0.0001), group (P<0.0023) and time * group interaction effects (P<0.0013). Continuous measurements of renal medullary blood flow (RMBF, L‐D) in two groups (SS and db‐cAMP) of an independent series showed that for the 60 min after rm DIVE the %ΔRMBF had fallen 34 ± 9 % in SS group while this variable did not change in db‐cAMP group (10 ± 9 %).CONCLUSIONSThe results suggest that db‐cAMP abolished the RIHP response to rm DIVE with SS by maintaining the baseline RMBF and/or by inhibiting the renal interstitial reactive response to rm DIVE with SS.Support or Funding InformationC13‐FAI‐03‐36.36/UASLP Subcapsular RIHP (mmHg) Group Before last 10 s 20'After 40'After 60'After CTR 1.8 ± 0.1 1.4 ± 0.1 1.8 ± 0.3 1.9 ± 0.3 2.1 ± 0.4 SS 1.5 ± 0.2 2.4 ± 0.6 3.7 ± 0.9• 5.3 ± 1.1◆• 5.7 ± 1.2◆• db‐cAMP 2.2 ± 0.4 2.5 ± 0.6 2.7 ± 0.5 3.0 ± 0.6♦ 2.8 ± 0.5