Interactions between nitric oxide and superoxide on the neural regulation of proximal fluid reabsorption in hypertensive rats

Abstract

This study investigated the role of nitric oxide (NO) and superoxide anions in modulating the renal nerve-dependent increases in proximal tubular fluid reabsorption (Jva). Renal nerve stimulation at 0.75 and 1.0 Hz (15 V, 0.2 ms) in anaesthetized Wistar rats had no effect on glomerular filtration rate but decreased urine flow and sodium excretion in a frequency-related manner, reaching 39 and 49% at 1.0 Hz, respectively (P < 0.01) and increased Jva by 11 and 31% (P < 0.01). In the stroke prone spontaneously hypertensive rats (SHRSP), basal mean blood pressure was higher (123 ± 2 versus 99 ± 2 mmHg, P < 0.001), glomerular filtration rate, urine flow, sodium excretion and proximal tubular fluid reabsorption (Jva) were lower (all P < 0.001) than in the Wistar rats. Renal nerve stimulation in the SHRSP did not change glomerular filtration rate but decreased urine flow, and sodium excretion by 18 and 34% (P < 0.05) at 1.0 Hz which was less (P < 0.05) than that in the Wistar rats. Under these conditions, Jva was increased at 0.75 Hz by 27%, and to a comparable extent at 1.0 Hz, which was a pattern very different from the frequency related rises reported in the Wistar rats. In the SHRSP, intratubular Nω-nitro-L-arginine methyl ester (L-NAME) had no effect on baseline Jva or the pattern of response to renal nerve stimulation which contrasted with earlier reports in the Wistar rat. Intraluminal superoxide dismutase (SOD) had no effect on basal Jva in the Wistar rats but increased it in the SHRSP (P < 0.05) while the pattern of change in Jva during nerve stimulation was unaltered in both rat strains. By contrast, in the SHRSP, intraluminal sodium nitroprusside (SNP) resulted in a frequency related increase in Jva comparable to that obtained in the vehicle treated Wistar rats. These data suggest that in the hypertensive rats, superoxide anion production is raised which depresses Jva and interacts with NO preventing a normal Jva response to renal nerve stimulation.

Renal Proximal Tubular Reabsorption Is Reduced In Adult Spontaneously Hypertensive Rats

“…J v was also lower in adult stroke-prone SHR4, compared to WKY. This may be related to increased reactive oxygen species (ROS), since direct microperfusion of reducing agents corrected this dysfunction4. The SHR is indeed an established model of oxidative stress, with elevated superoxide levels and NADPH oxidase expression in both vascular and renal tissue 5.…”

“…For example, in 7 and 12 week old SHR, at a time when hypertension was established, baseline J v in the proximal tubule was lower compared to WKY3. J v was also lower in adult stroke-prone SHR4, compared to WKY. This may be related to increased reactive oxygen species (ROS), since direct microperfusion of reducing agents corrected this dysfunction4.…”

Increased responsiveness to JNK1/2 mediates the enhanced H2O2-induced stimulation of Cl−/HCO3− exchanger activity in immortalized renal proximal tubular epithelial cells from the SHR

“…We previously showed that SHR PTE cells have an enhanced sensitivity to H 2 O 2 -induced stimulation of Cl -/HCO 3 -exchanger activity when compared with WKY PTE cells [20] while previous studies on the effect of ROS on proximal tubule transport involved superoxide [12,13]. In an attempt to determine the mechanisms responsible for differences in H 2 O 2 sensitivity between renal PTE cells from hypertensive and normotensive rats, the present study examined the role of the major mitogen-activated protein kinase (MAPK) signalling pathways.…”

“…The effect of ROS in renal proximal tubule is not well established. Indeed, superoxide has been reported to decrease renal proximal tubule transport by inhibiting NHE3 activity in the adult SHR [12,13].…”

Angiotensin II-mediated biphasic regulation of proximal tubular Na+/H+ exchanger 3 is impaired during oxidative stress

“…Although increased proximal tubular fluid and sodium reabsorption could contribute to sodium retention and development of hypertension in SHR, the overactive sodium transport is not seen in older SHR (4). Also, there are reports that either failed to show difference in sodium reabsorption between adult SHR and Wistar-Kyoto rats or observed reduced proximal tubular fluid reabsorption and NHE3 activity in SHR (4,23,31). The exact mechanisms for these discrepancies are not clear; however, it is possible that age or strain difference could play an important role in renal sodium regulation.…”