Baroreflex Control of Renal Sympathetic Nerve Activity and Renal Responses to Volume Expansion Following Intermittent Hypoxia in Rats
Authors: AlMarabeh Sara , O’Neill Julie , Cavers Jeremy , Lucking Eric F. , O’Halloran Ken D. , Abdulla Mohammed H. 
Published: April 2020

The baroreceptor reflex provides negative‐feedback control to reduce blood pressure fluctuations. Dysfunction of the baroreflex was reported in hypertension disease models that involve kidney injury. This study investigated the high‐ and low‐pressure baroreflex control of renal sympathetic nerve activity (RSNA), in addition to renal diuretic and natriuretic responses to volume expansion (VE) in rats exposed to intermittent hypoxia (IH). Wistar rats were exposed to IH (210 sec at 21% O2 and 90 sec at 6% O2, 12 cycles/hr, n=9) or to normoxia (sham, 21% O2, n=8) for 14 days. On day 15, rats were anaesthetized (induction: urethane, α‐chloralose and sodium pentobarbitone mixture i.p. (416, 27 and 33mg/kg), maintenance: urethane and α‐chloralose mixture i.v.) and prepared to record cardiovascular parameters and RSNA, and measure renal sodium and water excretory function. High‐pressure baroreflex was assessed using i.v. injections of phenylephrine and sodium nitroprusside (50μg/kg/min) to induce blood pressure changes. RSNA was calculated as a percentage of baseline values and plotted against mean arterial blood pressure. Low‐pressure baroreflex was studied using two successive VE challenges (0.25ml saline/100g body weight/min for 30min i.v.) during which saline or capsaizepine (CPZ, 5μg/ml/hr), a TRPV1 blocker were infused intra‐renally and the RSNA sympatho‐inhibitory response was recorded. Urine samples were collected to measure urine flow rate (UFR) and absolute Na + excretion (UNa+). Data are expressed as mean±SD and analyzed using t‐test or ANOVA where relevant. IH rats had higher blood pressure (97±11 vs. 84±9 mmHg) and RSNA to maximum RSNA ratio (0.36±0.15 vs. 0.17±0.07, all p<0.05), compared with sham. The slope (sensitivity) of the baroreflex gain curve of RSNA was smaller (0.09±0.05 vs. 0.29±0.27 a.u./mmHg, p=0.016) while the operating pressure was greater (129±14 vs. 109±6 mmHg, p=0.005) in IH rats compared with sham. VE decreased RSNA during the 30 min period from baseline to an equivalent extent (−35%) in sham and IH groups. However, VE‐induced increase in UFR (p=0.015) and UNa+ (p=0.02) was blunted after 30 min of VE challenge in IH rats compared with sham. This was revealed by a decrease in the area under UFR (5875±1574 vs. 9785±2714 ml/kg, p=0.002) and UNa+ (467±120 vs. 655±249 μmol, p=0.062) curves of IH rats compared with sham. Intra‐renal CPZ increased UFR (AUC; IH, 9868±4098 vs. sham, 10157±4081 ml/kg) and UNa+ (AUC, IH, 612±217 vs. sham, 721±223 μmol) in the IH group to comparable levels of sham. This was associated with potentiation of RSNA sympatho‐inhibition response to VE by 54% (p<0.05) in both groups. There was no evidence of oxidative stress or inflammation in IH kidneys. These findings suggest that moderate IH exposure blunts baroreflex regulation of RSNA. Renal diuretic and natriuretic responses to VE were perturbed by IH exposure although low‐pressure baroreflex control of RSNA was preserved. TRPV1 blockade restored the blunted excretory response to VE in IH rats.