Highly suggestive preliminary evidence that the renal interstitium contracts in vivo

Abstract

To learn more about controlling renal interstitial hydrostatic pressure (RIHP), we assessed its response to renal medullary direct interstitial volume expansion (rmDIVE = 100 μL bolus infusion/30 sec). Three experimental series (S) were performed in hydropenic, anesthetized, right‐nephrectomized, acute left renal‐denervated and renal perfusion pressure‐controlled rats randomly assigned to groups in each S. S1: Rats without hormonal clamp were contrasted before and after rmDIVE induced via 0.9% saline solution bolus (SS group) or 2% albumin in SS bolus (2% ALB + SS group). Subcapsular ΔRIHP rose slowly, progressively and similarly in both groups by ~3 mmHg. S2: Rats under hormonal clamp were contrasted before and after sham rmDIVE (time CTR group) and real rmDIVE induced via either SS bolus (SS group) or SS bolus containing the subcutaneous tissue fibroblast relaxant dibutyryl‐cAMP (SS + db‐cAMP group). ΔRIHP showed time, group, and time*group interaction effects with a biphasic response (early: ~1 mmHg; late: ~4 mmHg) in the SS group that was absent in the SS + db‐cAMP group. S3: Two groups of rats (SS and SS + db‐cAMP) under hormonal clamp were contrasted as in S2, producing similar ΔRIHP results to those of S2 but showing a slow, progressive, and indistinct decrease in renal outer medullary blood flow in both groups. These results provide highly suggestive preliminary evidence that the renal interstitium is capable of contracting reactively in vivo in response to rmDIVE with SS and demonstrate that such a response is abolished when db‐cAMP is interstitially and concomitantly infused.

Additional evidence that the rat renal interstitium contracts in vivo

“…Given the sui-generis architecture of the renal interstitium [1] and supported both in the well-known phenomenon of cellular subcutaneous tissue contraction [2] and in the fact that renal medullary interstitial cells in culture contract in response to endothelin and arginine vasopressin [3], we recently provided [4] highly suggestive preliminary evidence that the renal interstitium contracts reactively in vivo . We reported that, in hydropenic rats subjected to left renal denervation, hormonal clamping, and renal arterial pressure control, the renal medullary Direct Interstitial Volume Expansion ( rmDIVE ) induced by a 0.9% saline bolus infusion (100 μL / 30 s) into the left renal medullary interstitium brought about a biphasic renal interstitial hydrostatic pressure (RIHP) response (early: ~1 mmHg and late: ~ 4 mmHg).…”

“…The next step in the present study was to determine the ideal volume of the micro-bolus to be injected and the effective dose of α-TNS for a single local renal injection. To avoid inducing significant rmDIVE via a 100 μl bolus infusion of SS, which by itself increases RIHP [4], preliminary experiments suggested the use of a sudden 3–5 μl micro-bolus injection. We exploited the countercurrent drug-trapping mechanism present in the renal medullary interstitium, which enables drugs to be retained longer with very small quantities escaping into systemic circulation [15].…”

“…Considering the additional six pharmacokinetic elements described in the Material and Methods section of the present study, we decided to conduct preliminary testing on the effectiveness of two doses of α-trinositol (2 and 4 mM) integrated into the micro-boluses of SS (Series 1, SS + 2 mM and SS + 4 mM groups). On the basis of the positive association between BL RIHP and EXP RIHP [4] and the similarity of BL RIHP values among the groups, we focused more on the time course for ΔRIHP than the time course for absolute RIHP. A similar maximal increase of ΔRIHP and a similar maximal decrease of %ΔRoMBF were found with both α-TNS doses, with no overall differences observed in the time courses for ΔRIHP and %ΔRoMBF between groups.…”

“…Once in place, a fat pad placed at the probe insertion point sealed the renal capsule. Finally, a homemade, heparinized, unbevelled, PE-10 subcapsular catheter was implanted to measure RIHP [4, 8], and once in place, a micro-drop of cyanoacrylate was deposited between the catheter and the kidney capsule to avoid leaks. To be included in the analysis, an experiment had to show, after surgery and before finishing the experiment, a quick RIHP increase of at least 20 mmHg after ~ 5 s of renal vein occlusion, followed by a quick return to the baseline after renal vein disocclusion.…”

“…We reported that, in hydropenic rats subjected to left renal denervation, hormonal clamping, and renal arterial pressure control, the renal medullary Direct Interstitial Volume Expansion ( rmDIVE ) induced by a 0.9% saline bolus infusion (100 μL / 30 s) into the left renal medullary interstitium brought about a biphasic renal interstitial hydrostatic pressure (RIHP) response (early: ~1 mmHg and late: ~ 4 mmHg). When 5mM dibutyryl-cAMP (db-cAMP) was concomitant and interstitially infused, this response was abolished and was not accompanied by any differential changes among groups in the time course of the haematocrit, serum protein concentration, or renal outer medullary blood flow [4]…”