Intrarenal Dopaminergic System Is Dysregulated in SS- Rats

Authors

Usman M. Ashraf, Department of Physiology and Pharmacology, University of Toledo College of Medicine and Life Sciences, Toledo, OH 43614, USA.
Ealla Atari, Department of Physiology and Pharmacology, University of Toledo College of Medicine and Life Sciences, Toledo, OH 43614, USA.
Fawaz Alasmari, Department of Pharmacology and Experimental Therapeutics, University of Toledo College of Pharmacy & Pharmaceutical Sciences, Toledo, OH 43614, USA.
Harshal Waghulde, Department of Physiology and Pharmacology, University of Toledo College of Medicine and Life Sciences, Toledo, OH 43614, USA.
Vikash Kumar, Department of Physiology, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
Youssef Sari, Department of Pharmacology and Experimental Therapeutics, University of Toledo College of Pharmacy & Pharmaceutical Sciences, Toledo, OH 43614, USA.
Sonia M. Najjar, Department of Biomedical Sciences, Heritage College of Osteopathic Medicine, Ohio University, Athens, OH 45701, USA.
Pedro A. Jose, Department of Medicine, Division of Kidney Diseases & Hypertension, The George Washington University School of Medicine & Health Sciences, Washington, DC 20052, USA.
Sivarajan Kumarasamy, Department of Physiology and Pharmacology, University of Toledo College of Medicine and Life Sciences, Toledo, OH 43614, USA.

Document Type

Journal Article

Publication Date

1-1-2023

Journal

Biomedicines

Volume

11

Issue

1

DOI

10.3390/biomedicines11010111

Keywords

Dahl salt-sensitive rats; Resp18; blood pressure; dopamine; kidney

Abstract

The genetic and molecular basis of developing high blood pressure and renal disease are not well known. Dahl salt-sensitive (SS-) rats fed a 2% NaCl diet for six weeks have high blood pressure, increased renal fibrosis, and decreased mean survival time. Impairment of the dopaminergic system also leads to hypertension that involves renal and non-renal mechanisms. Deletion of any of the five dopamine receptors may lead to salt-sensitive hypertension. Therefore, we investigated the interaction between and renal dopamine in SS- and Dahl salt-sensitive (SS) rats. We found that SS- rats had vascular dysfunction, as evidenced by a decrease in vasorelaxation in response to sodium nitroprusside. The pressure-natriuresis curve in SS- rats was shifted down and to the right of SS rats. SS- rats had decreased glomerular filtration rate and dopamine receptor subtypes, D1R and D5R. Renal dopamine levels were decreased, but urinary dopamine levels were increased, which may be the consequence of increased renal dopamine production, followed by secretion into the tubular lumen. The increased renal dopamine production in SS- rats in vivo was substantiated by the increased dopamine production in renal proximal tubule cells treated with L-DOPA. Overall, our study provides evidence that targeted disruption of the locus in the SS rat dysregulates the renal dopaminergic system.

APA Citation

Ashraf, Usman M.; Atari, Ealla; Alasmari, Fawaz; Waghulde, Harshal; Kumar, Vikash; Sari, Youssef; Najjar, Sonia M.; Jose, Pedro A.; and Kumarasamy, Sivarajan, "Intrarenal Dopaminergic System Is Dysregulated in SS- Rats" (2023). GW Authored Works. Paper 2316.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/2316

Department

Medicine