Abstract: PO1819
The Role of Histaminergic System Components in Renal Function During Salt-Sensitive Hypertension
Session Information
- Hypertension and CVD: Mechanisms
November 04, 2021 | Location: On-Demand, Virtual Only
Abstract Time: 10:00 AM - 12:00 PM
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