ASN's Mission

ASN leads the fight to prevent, treat, and cure kidney diseases throughout the world by educating health professionals and scientists, advancing research and innovation, communicating new knowledge, and advocating for the highest quality care for patients.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005

email@asn-online.org

202-640-4660

The Latest on Twitter

Kidney Week

Abstract: PO2486

Circadian Cycle Exaggerates Sympathoexcitatory Responses to Activation of Chemosensitive Renal Sensory Nerves

Session Information

Category: CKD (Non-Dialysis)

  • 2103 CKD (Non-Dialysis): Mechanisms

Authors

  • DeLalio, Leon J., University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States
  • Stocker, Sean D., University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States
Background

Renal sensory nerves contribute to renovascular hypertension and renal dysfunction in chronic kidney disease. These sensory nerves are activated by chemokines (e.g., bradykinin and capsaicin) and produce reflexive changes in efferent sympathetic nerve activity (SNA) and arterial blood pressure (ABP). SNA, renal function, and ABP exhibit clear circadian patterns. Yet, it is unknown whether the circadian cycle alters renal-reflex responses to chemosensitive stimuli. We hypothesized renal sensory nerve activation would elicit larger SNA and hemodynamic responses during the dark versus the light periods.

Methods

To test this hypothesis, male and female Sprague-Dawley rats (250-400g) were anesthetized with Inactin and prepared for simultaneous nerve recordings of renal and splanchnic SNA and ABP at dark (D; 20:00-04:00; n= 12M, 10F) and light (L; 09:00-16:00; n= 8M, 8F) periods.

Results

Intrarenal capsaicin infusion (0.1μM – 30.0μM; 50μl over 15s) produced concentration-dependent increases in renal and splanchnic SNA in both the dark and light periods. Interestingly, a greater increase in renal SNA in dark versus light groups occured with 10 μM (D: 723±136 vs L: 409±79 %; p=0.03) and 30 μM (D: 826±181 vs L: 509±80 %; p=0.03) capsaicin. Intrarenal capsaicin produced greater increases in splanchnic SNA between dark versus light periods at 10 μM (D: 501±117 vs L: 204±53 %, p=0.03) and 30 μM (D: 537±101 vs L: 295±68 %; p=0.03). ABP was similarly increased during the dark (7±1 mmHg; 30 μM) and light (6±1 mmHg; 30 μM) periods.

Intrarenal bradykinin infusion (0.1μM – 30.0μM; 50μl over 15s) produced concentration-dependent increases in renal and splanchnic SNA in both the dark and light periods. A greater increase in renal SNA during the dark versus light periods occured at 10 μM (D: 1773±216 vs L: 1249±112 %; p=0.01) and 30uM (D: 2605±263 vs L: 1783±163 %; p=0.001). Splanchnic SNA responses were also greater during the dark versus light periods at 0.1 μM (D: 163±65 vs L: 0±0 %; p=0.02), 1.0 μM (D: 566±114 vs L: 184±52 %; p=0.005), 10 μM (D: 1110±193 vs L: 583±87 %; p=0.006) and 30 μM (D: 2008±193 vs L: 1044±162 %; p<0.001). ABP was similarly increased between the dark (10±2 mmHg; 30 μM) and light (6±1 mmHg; 30 μM) periods.

Conclusion

Thus, the circadian cycle exaggerates sympathoexcitatory responses produced by activation of chemosensitive renal sensory nerves.

Funding

  • NIDDK Support