Abstract: SA-PO1075

Renal Oxygenation during Chronic Nitric Oxide Synthase Inhibition as Recorded by Telemetry

Session Information

Category: Hypertension

  • 1102 Hypertension: Basic and Experimental - Renal Causes and Consequences

Authors

  • Emans, Tonja, AMC-UvA, Amsterdam, Netherlands
  • Joles, Jaap A., UMC Utrecht, Utrecht, Netherlands
  • Krediet, C.T.P. (Paul), AMC-UvA, Amsterdam, Netherlands
Background

Renal hypoxia has been advanced as a crucial factor in the vicious circle of disease progression leading to kidney failure. Nitric oxide (NO) is involved in renal vascular regulation. NO synthase (NOS)-inhibition leads to hypertension while decreasing renal blood flow and thus oxygen delivery. Furthermore, NO inhibits mitochondrial oxygen consumption. Therefore, we hypothesized that NOS inhibition would induce renal hypoxia. We now report telemetrically monitored mean arterial pressure and oxygen pressure (pO2) in renal cortex and medulla in conscious rats during chronic NOS inhibition.

Methods

Oxygen sensitive electrodes were implanted in either renal cortex (n=6) or medulla (n=7) in healthy rats. After recovery and stabilization, baseline pO2 was recorded for one week. Then, to inhibit NOS, L-NNA (40mg/kg/day) was administered via drinking water for two weeks. A separate group of rats (n=6), instrumented with blood pressure recording telemeters, followed the same protocol. Terminal glomerular filtration rate (GFR), renal blood flow (RBF), renal oxygen extraction and natriuresis were assessed under isoflurane anesthesia in all L-NNA rats (n=19) and in untreated controls (n=6).

Results

NOS inhibition rapidly induced hypertension (164 ± 6 vs. 108 ± 3 mmHg, p<0.001) and progressive proteinuria (82 ± 13 vs. 17 ± 2 mg/day, p<0.01). After an initial dip, cortical oxygenation returned to baseline. In contrast, medullary oxygenation decreased progressively (up to -23 ± 8% vs. baseline; p<0.05). Terminal GFR (1334 ± 74 vs. 2036 ± 166 µl/min) and RBF (4840 ± 343 vs. 8986 ± 938 µl/min) were reduced vs. control (both p<0.01). Terminal sodium reabsorption efficiency (TNa/QO2) also decreased (12.7 ± 1.1 vs. 22.8 ± 2.2 µmol/µmol, p<0.01).

Conclusion

Chronic NOS inhibition induced temporal changes in renal pO2. Cortical pO2 was not persistently altered, despite reduced RBF and therefore oxygen supply. In contrast, medullary pO2 decreased progressively. Chronic NO deficiency leads to decreased renal perfusion and reabsorption efficiency (possibly of mitochondria) resulting in progressive medullary hypoxia. This suggests that juxtamedullary nephrons are particularly sensitive to chronic NO depletion.

Supported by: Netherlands Organisation for Health Research (ZonMW, 40007039712461)

Funding

  • Government Support - Non-U.S.