Renal nerves and hypertension contribute to impaired proximal tubule megalin-mediated albumin uptake in renovascular hypertensive rats

Author(s)

Veiga, A. C. ; Silva-Aguiar, R. P. ; Milanez, M. I. O. ; Aires, R. S. ; Moraes, Y. A. C. ; Campos, R. R. ; Bergamaschi, C. T. ; Caruso-Neves, C. ; Nishi, E. E.

• Document type: Journal article
• Source: HYPERTENSION RESEARCH; v. N/A, p. 12-pg., 2025-01-17.

Abstract

Proteinuria, especially albuminuria, serves as an independent risk factor for progression in cardiovascular and renal diseases. Clinical and experimental studies have demonstrated that renal nerves contribute to renal dysfunction in arterial hypertension (AH). This study hypothesizes that renal nerves mediate the mechanisms of protein endocytosis by proximal tubule epithelial cells (PTEC) and glomerular function; with dysregulation of the renal nerves contributing to proteinuria in Wistar rats with renovascular hypertension (2-kidney, 1-clip model, 2K-1C). Reduced albumin uptake and increased internalization of endocytic receptor megalin in PTEC were found in both the clipped and contralateral kidneys of 2K-1C rats. Renal denervation (DNx) or hydralazine treatment restored these parameters. Moreover, DNx, but not hydralazine, reduced serum creatinine and recovered podocyte numbers in the contralateral kidney of 2K-1C rats. Thus, our data suggest that renal nerves and high arterial pressure contribute to decreased albumin reabsorption by cellular redistribution of megalin in PTEC, while renal nerves remarkably drive glomerular dysfunction in renovascular hypertension, independently of their effect on blood pressure.Created with BioRender.com (AU)

• FAPESP's process: 19/25295-0 - Communication between the central nervous system and kidneys: cardiovascular, renal and autonomic influences in physiological and physiopathological conditions
• Grantee: Ruy Ribeiro de Campos Junior
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 22/11063-2 - Effects of bone marrow with high myeloid ACE expression on the metabolism of adipose tissue and cardiovascular parameters in obese mice
• Grantee: Erika Emy Nishi
• Support Opportunities: Scholarships abroad - Research
• FAPESP's process: 20/02617-9 - Mechanisms involved in renal protein reabsorption in Renovascular Hypertension: a role for the renal nerve
• Grantee: Amanda Costa Veiga
• Support Opportunities: Scholarships in Brazil - Doctorate