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: PO1819

The Role of Histaminergic System Components in Renal Function During Salt-Sensitive Hypertension

Session Information

Category: Hypertension and CVD

  • 1403 Hypertension and CVD: Mechanisms

Authors

  • Spires, Denisha R., Augusta University, Augusta, Georgia, United States
  • Domondon, Mark, Medical University of South Carolina, Charleston, South Carolina, United States
  • Schibalski, Ryan, Augusta University, Augusta, Georgia, United States
  • Perez, Samantha M., Medical University of South Carolina, Charleston, South Carolina, United States
  • Fomin, Mikhail, Augusta University, Augusta, Georgia, United States
  • Spicer, Morgan J., Augusta University, Augusta, Georgia, United States
  • Arkhipov, Sergey N., Henry Ford Health System, Detroit, Michigan, United States
  • Clarke, Callie A., Medical University of South Carolina, Charleston, South Carolina, United States
  • Amoah, Thelma, Medical University of South Carolina, Charleston, South Carolina, United States
  • Pavlov, Tengis S., Henry Ford Health System, Detroit, Michigan, United States
  • Ilatovskaya, Daria, Augusta University, Augusta, Georgia, United States
Background

Up to 50% of hypertensive patients have salt-sensitivity (SS), a condition characterized with an increase in blood pressure in response to salt intake. The abnormal activation of the immune response is a major contributor to SS hypertension and renal injury. Histamine and its receptors (HRs) are a complex system of immunoregulators that have been linked to renal disease development. It is known that the Dahl SS rat fed a high salt diet develops hypertension accompanied with elevated levels of inflammatory factors. We hypothesize that HRs and associated enzymes contribute to renal disease progression during SS hypertension.

Methods

Male Dahl SS rats at 8 weeks of age were placed on either a 0.4% (normal salt; NS, control) or 4% (high salt; HS, hypertensive group) NaCl diet for 21 days to induce SS hypertension. An additional group of animals received 3 injections of ranitidine (RAN; HR2 blocker; 25 mg/kg) or saline (VEH; 2.5 mL/kg) pre- and post- the HS challenge to test the effects of HR2 blockage on renal function.

Results

Using immunohistochemistry, we established the expression of all four HRs as well as histamine-metabolizing and catabolizing enzymes, along the nephron with a pronounced expression in the glomerulus, proximal tubule and the distal tubules. Interestingly, we observed a decrease in histidine decarboxylase, and an increase in histamine N-methyltransferase in the kidney of HS diet fed rats, suggesting a shift in renal histaminergic tone. RAN treatment pre-HS resulted in a significant decrease in urine volume (1.89 ± 0.20 vs 1.60 ± 0.18 mL/100g, p=0.012, in VEH vs RAN groups respectively) and water consumption (14.3 ± 2.25 vs 11.9 ± 1.69 mL), along with elevated Cl- excretion (728.4 ± 287.4 µM vs 1107.8 ± 416.6 uMol). Post-HS RAN treatment yielded a significant increase in urine osmolality (1313.2 ± 319.7 vs 1659.5 ± 359.2 mOsm).

Conclusion

Thus far, we report a shift in the histaminergic tone toward less histamine production in the Dahl SS rat fed a HS diet. Dahl SS rats acutely treated with H2R blocker exhibit lower water consumption, reduced diuresis, and increased urinary osmolality.

Funding

  • Other NIH Support