A high-salt diet enhances leukocyte adhesion in association with kidney injury in young Dahl salt-sensitive rats

• Published in: Hypertension research 2017-11, Vol.40 (11), p.912-920
• Main Authors: Takahashi, Hidenori, Nakagawa, Suguru, Wu, Yaqiong, Kawabata, Yukari, Numabe, Atsushi, Yanagi, Yasuo, Tamaki, Yasuhiro, Uehara, Yoshio, Araie, Makoto
• Format: Article
• Language: English
• Subjects: Animals; Biosynthesis; Blood Pressure - drug effects; Cell Adhesion - drug effects; Cell Adhesion - physiology; Chemokine CCL2 - metabolism; Hypertension; Intercellular Adhesion Molecule-1 - metabolism; Kidney - drug effects; Kidney - metabolism; Kidney Diseases - metabolism; Leukocytes - drug effects; Leukocytes - metabolism; Original; Rats; Rats, Inbred Dahl; Rodents; Salt; Sodium, Dietary - pharmacology
• ISSN: 0916-9636; 1348-4214
• DOI: 10.1038/hr.2017.31

Salt-sensitive hypertension is associated with severe organ damage. Generating oxygen radicals is an integral component of salt-induced kidney damage, and activated leukocytes are important in oxygen radical biosynthesis. We hypothesized that a high-salt diet causes the upregulation of immune-related mechanisms, thereby contributing to the susceptibility of Dahl salt-sensitive rats to hypertensive kidney damage. For verifying the hypothesis, we investigated leukocytes adhering to retinal vessels when Dahl salt-sensitive rats were challenged with a high-salt (8% NaCl) diet using acridine orange fluoroscopy and a scanning laser ophthalmoscope. The high-salt diet increased leukocyte adhesion after 3 days and was associated with a significant increase in mRNA biosynthesis of monocyte chemotactic protein-1 and intercellular adhesion molecule-1 (ICAM-1) -related molecules in the kidney. Losartan treatment did not affect increased leukocyte adhesion during the early, pre-hypertensive phase of high salt loading; however, losartan attenuated the adhesion of leukocytes during the hypertensive stage. Moreover, the inhibition of leukocyte adhesion in the pre-hypertensive stage by anti-CD18 antibodies decreased tethering of leukocytes and was associated with the attenuation of functional and morphological kidney damage without affecting blood pressure elevation. In conclusion, a high-salt challenge rapidly increased leukocyte adhesion through the over-expression of ICAM-1. Increased leukocyte adhesion in the pre-hypertensive stage is responsible for subsequent kidney damage in Dahl salt-sensitive rats. Immune system involvement may be a key component that initiates kidney damage in a genetic model of salt-induced hypertension.