Down-regulation of the intrarenal renin-angiotensin system in the aging rat

F. F. Jung, T. M. Kennefick, J. R. Ingelfinger, J. P. Vora, Sharon Anderson

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

Progressive deterioration of renal function occurs during normal aging. Previous studies on the aging kidney have demonstrated glomerular hemodynamic changes, specifically, glomerular capillary hypertension, as maladaptations that lead to proteinuria and glomerular sclerosis over time. Aging rats treated with angiotensin-converting enzyme inhibition have relatively less proteinuria and sclerosis, suggesting that age-related changes in renal function may be associated with alterations in the intrarenal renin-angiotensin system, which thus may play a major role in the pathogenesis of these maladaptations. To investigate this possibility, renal and systemic renin-angiotensin systems were examined at an early phase of the aging process (3 months) and at a later phase (12 months) in male Sprague-Dawley rats. Although plasma renin and serum angiotensin-converting enzyme concentrations did not differ significantly, the intrarenal system showed down-regulation of renin mRNA and angiotensin-converting enzyme levels with aging, whereas angiotensinogen levels remained stable. The decrease in renin mRNA appeared to precede the fall in plasma renin concentration in the aging process. Additional studies in 15-month-old rats confirmed that, by this time, both basal and stimulated renal renin release rates were impaired in older rats. Thus, both decreased renin synthesis and impaired renin release underlie the fall in plasma renin with normal aging. This decrease may act to lower intrarenal baseline levels of angiotensin II, an adaptation of likely importance in the modulation of intrarenal vascular tone and tubular function in the aging kidney.

Original languageEnglish (US)
Pages (from-to)1573-1580
Number of pages8
JournalJournal of the American Society of Nephrology
Volume5
Issue number8
StatePublished - 1995
Externally publishedYes

Fingerprint

Renin-Angiotensin System
Renin
Down-Regulation
Kidney
Peptidyl-Dipeptidase A
Sclerosis
Proteinuria
Angiotensinogen
Messenger RNA
Angiotensin II
Blood Vessels
Sprague Dawley Rats
Hemodynamics
Hypertension
Serum

Keywords

  • angiotensin-converting enzyme
  • elderly
  • kidney
  • renin release

ASJC Scopus subject areas

  • Nephrology

Cite this

Jung, F. F., Kennefick, T. M., Ingelfinger, J. R., Vora, J. P., & Anderson, S. (1995). Down-regulation of the intrarenal renin-angiotensin system in the aging rat. Journal of the American Society of Nephrology, 5(8), 1573-1580.

Down-regulation of the intrarenal renin-angiotensin system in the aging rat. / Jung, F. F.; Kennefick, T. M.; Ingelfinger, J. R.; Vora, J. P.; Anderson, Sharon.

In: Journal of the American Society of Nephrology, Vol. 5, No. 8, 1995, p. 1573-1580.

Research output: Contribution to journalArticle

Jung, FF, Kennefick, TM, Ingelfinger, JR, Vora, JP & Anderson, S 1995, 'Down-regulation of the intrarenal renin-angiotensin system in the aging rat', Journal of the American Society of Nephrology, vol. 5, no. 8, pp. 1573-1580.
Jung, F. F. ; Kennefick, T. M. ; Ingelfinger, J. R. ; Vora, J. P. ; Anderson, Sharon. / Down-regulation of the intrarenal renin-angiotensin system in the aging rat. In: Journal of the American Society of Nephrology. 1995 ; Vol. 5, No. 8. pp. 1573-1580.
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