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.

Epidemiological and experimental evidence recognize a relationship between sleep-wake cycles and adiposity levels, but the mechanisms that link both are not entirely understood. Adipose tissue secretes adiponectin and leptin hormones, mainly involved as indicators of adiposity levels and recently associated to sleep. To understand how two of the main adipose tissue hormones could influence sleep-wake regulation, we evaluated in male rats, the effect of direct administration of adiponectin or leptin in the ventrolateral preoptic nuclei (VLPO), a major area for sleep promotion. The presence of adiponectin (AdipoR1 and AdipoR2) and leptin receptors in VLPO were confirmed by immunohistochemistry. Adiponectin administration increased wakefulness during the rest phase, reduced delta power, and activated wake-promoting neurons, such as the locus coeruleus (LC), tuberomammillary nucleus (TMN) and hypocretin/orexin neurons (OX) within the lateral hypothalamus (LH) and perifornical area (PeF). Conversely, leptin promoted REM and NREM sleep, including increase of delta power during NREM sleep, and induced c-Fos expression in VLPO and melanin concentrating hormone expressing neurons (MCH). In addition, a reduction in wake-promoting neurons activity was found in the TMN, lateral hypothalamus (LH) and perifornical area (PeF), including in the OX neurons. Moreover, leptin administration reduced tyrosine hydroxylase (TH) immunoreactivity in the LC. Our data suggest that adiponectin and leptin act as hormonal mediators between the status of body energy and the regulation of the sleep-wake cycle.

We recently provided highly suggestive preliminary evidence that the renal interstitium contracts reactively in vivo. We demonstrated that renal medullary direct interstitial volume expansion (rmDIVE = 100 μl bolus infusion of 0.9% saline (SS)/30 s) brought about a biphasic renal interstitial hydrostatic pressure (RIHP) response which was abolished when dibutyryl-cAMP was concomitant and interstitially infused. To assess more deeply the feasibility of the concept that the renal interstitium contracts in vivo, two experimental series (S1, S2) were performed in hydropenic rats subjected to acute left renal-denervation, hormonal clamping, and control of renal arterial pressure. In S1, RIHP and renal outer medullary blood flow (RoMBF) were continuously measured before and after a sudden micro-bolus (5μl) injection, into the renal medullary interstitium, of SS containing α-trinositol (α-TNS, anti-inflammatory drug) to either two doses 2 or 4 mM (SS + 2 α-TNS and SS + 4 α-TNS groups). No overall differences between groups in either ΔRIHP or %ΔRoMBF time courses were found; however, in the SS + 2 α-TNS group the data were less scattered and the ΔRIHP time course tended to peak faster and then persisted there, so that, this α-TNS dose was selected for S2. In S2, RIHP and RoMBF were similarly measured in rats randomly assigned to three groups: the CTR group (sham time-control), SS group (SS alone), and SS + α-TNS group. The micro-bolus injection of SS alone (SS group) was unable to increase ΔRIHP. The group with no micro-bolus injection (CTR group) experienced a decrease in ΔRIHP. The micro-bolus injection of SS + 2 α-TNS was accompanied by a differential increase in ΔRIHP (vs. CTR and SS groups). These responses were not associated with differential changes among groups in %ΔRoMBF or hemodilution parameters. These results provide additional evidence that the renal interstitium contracts in vivo.

One of the hallmarks of the metabolic syndrome (MS) is the increase of renal sympathetic nerve activity (RSNA), which leads to the upregulation of the renin‐angiotensin system (RAS). Interestingly, the sympathetic hyperactivity in the kidney of obese humans often occurs in absence of overt systemic hypertension. The stimulation of RSNA contributes to the glomerular lesions and the progressive loss of nephron functionality, resulting in acute renal injury (AKI) and, in the long term, chronic kidney disease (CKD), which represent the most common complication of MS. Clinical evidence and animal models of MS have shown that renal sympathetic denervation (RSDN) induces a transient attenuation of the hypertensive symptoms, while the markers of kidney damage continue worsening. Therefore, it is likely that the renal derangement in MS might also depend on the metabolic impairment, such as the upregulation of plasma leptin and insulin, independently from the RSNA. To investigate this issue, we explored the effect of MS over blood pressure and kidney functionality, in intact and renal denervated rats. For that, animals were either fed with a standard diet (SD) or a high‐fat diet for 12 weeks (HFD), with or without bilateral renal denervation performed at the beginning of protocol (n = 6). Results indicate that, as expected, HFD in intact animals promotes fat accumulation, glucose intolerance and hypertension, but also decreases water consumption and induces marked proteinuria from week 7, slight hematuria from week 9, with respect to SD rats. Remarkably, the renal denervation prevents the changes that HFD triggered in blood pressure and renal parameters only in the short and medium term, but it is ineffective in the long term. On the bases of these results, we suggest that the hypertension associated to MS is not only due to hyperactivation of RSNA, but it could involve hormonal/hemodynamic factors, typical of metabolic impairment, which could contribute to renal injury.Support or Funding InformationCONACYT‐CB‐243298This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

RIHP increases after renal interstitial medullary injection (RIMI) of a 5μ bolus of saline solution (SS) + 2 μM α‐Trinositol (α –T, drug that increases collagen fiber network contraction, FASEB J 31:701.4: 2017). To assess whether this increase is induced by changes in the frequency and/or amplitude of oscillatory pattern of RIHP we evaluate in hydropenic rats the time course of RIHP before and after either an acute sham (CTR group, n = 9) or an acute (1s) real RIMI of a 5μ bolus of either vehicle (0.9% SS, SS group, n = 9) or SS + 2 μM α ‐ T (α – T group, n = 9). Left subcapsular RIHP (RIHP) was continuously measured (1 Hz) in anesthetized rats with right nephrectomy, acute left renal denervation, hormonal clamp and renal perfusion pressure control (100 mmHg), before (baseline phase = BL = 30 min) and 30 min after (experimental phase = EXP) sham or real RIMI of 5 μl bolus of either SS or SS + α‐T. The table shows the 30 min average BL RIHP (1800 s, s = samples or seconds), ΔRIHP (EXP RIHP – BL RIHP) values (mean ± SEM) obtained 30 min after sham or real RIMI during 300 s. It also shows the RIHP frequency (F) of major oscillations (cycles/min = cpm) and the standard deviation (SD, an oscillatory amplitude index) of global RIHP oscillation before and 30 min after RIMI. Three were no differences among groups in BL RIHP, F or SD. For ΔRIHP data there were time * group interaction effect (P < 0.009); * P = 0.05, ** P < 0.001 vs. BL; • P < 0.04 vs. SS group, ¨P < 0.001 vs. CTR group. For SD data ° P <0.001 between phases. CONCLUSIONS The results show that RIHP oscillates at an equally low frequency (≈ 0.03 Hz) before and after sham or real RIMI but with lower amplitude after sham or real RIMI in any of the groups. This suggests that α‐T increases RIHP but not through modify the frequency or amplitude of its low frequency oscillatory pattern. Support or Funding Information Own financial resources of Integrative Physiology Lab. RIHP RIHP RIHP (mmHg) Frequency SD Delta cpm (mmHg) BL EXP‐BL BL EXP BL EXP 30 min at min 30 last 5 min at min 30 30 min at min 30 Group 1800 s 300 s 300 s 300 s 1800 s 300 s CTR 3.0 ± 0.10 −1.1 ± 0.16 2.2 ± 0.26** 2.1 ± 0.26 0.54 ± 0.07 0.20 ± 0.04° SS 3.1 ± 0.03 −0.15 ± 0.36 2.1 ± 0.44 2.2 ± 0.46 0.50 ± 0.06 0.18 ± 0.03° a‐T 3.1 ± 0.06 1.26 ± 0.51 2.2 ± 0.32*•♦ 2.2 ± 0.25 0.35 ± 0.04 0.19 ± 0.04°