Impact of angiotensin type 1A receptors in principal cells of the collecting duct on blood pressure and hypertension

Daian Chen, Johannes Stegbauer, Matthew A. Sparks, Donald Kohan, Robert Griffiths, Marcela Herrera, Susan Gurley, Thomas M. Coffman

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

The main actions of the renin-angiotensin system to control blood pressure (BP) are mediated by the angiotensin type 1 receptors (AT1Rs). The major murine AT1R isoform, AT1AR, is expressed throughout the nephron, including the collecting duct in both principal and intercalated cells. Principal cells play the major role in sodium and water reabsorption. Although aldosterone is considered to be the dominant regulator of sodium reabsorption by principal cells, recent studies suggest a role for direct actions of AT1R. To specifically examine the contributions of AT1AR in principal cells to BP regulation and the development of hypertension in vivo, we generated inbred 129/SvEv mice with deletion of AT1AR from principal cells (PCKO). At baseline, we found that BPs measured by radiotelemetry were similar between PCKOs and controls. During 1-week of low-salt diet (<0.02% NaCl), BPs fell significantly (P<0.05) and to a similar extent in both groups. On a high-salt (6% NaCl) diet, BP increased but was not different between groups. During the initial phase of angiotensin II-dependent hypertension, there was a modest but significant attenuation of hypertension in PCKOs (163±6 mm Hg) compared with controls (178±2 mm Hg; P<0.05) that was associated with enhanced natriuresis and decreased alpha epithelial sodium channel activation in the medulla of PCKOs. However, from day 9 onward, BPs were indistinguishable between groups. Although effects of AT1AR on baseline BP and adaptation to changes in dietary salt are negligible, our studies suggest that direct actions of AT1AR contribute to the initiation of hypertension and epithelial sodium channel activation.

Original languageEnglish (US)
Pages (from-to)1291-1297
Number of pages7
JournalHypertension
Volume67
Issue number6
DOIs
StatePublished - Jun 1 2016
Externally publishedYes

Fingerprint

Angiotensin Type 1 Receptor
Blood Pressure
Hypertension
Epithelial Sodium Channels
Salts
Sodium
129 Strain Mouse
Sodium-Restricted Diet
Natriuresis
Nephrons
Renin-Angiotensin System
Aldosterone
Angiotensin II
Protein Isoforms
Diet
Water

Keywords

  • angiotensin AT receptor
  • angiotensin II
  • blood pressure
  • epithelial sodium channel blockers
  • hypertension

ASJC Scopus subject areas

  • Internal Medicine

Cite this

Chen, D., Stegbauer, J., Sparks, M. A., Kohan, D., Griffiths, R., Herrera, M., ... Coffman, T. M. (2016). Impact of angiotensin type 1A receptors in principal cells of the collecting duct on blood pressure and hypertension. Hypertension, 67(6), 1291-1297. https://doi.org/10.1161/HYPERTENSIONAHA.115.06987

Impact of angiotensin type 1A receptors in principal cells of the collecting duct on blood pressure and hypertension. / Chen, Daian; Stegbauer, Johannes; Sparks, Matthew A.; Kohan, Donald; Griffiths, Robert; Herrera, Marcela; Gurley, Susan; Coffman, Thomas M.

In: Hypertension, Vol. 67, No. 6, 01.06.2016, p. 1291-1297.

Research output: Contribution to journalArticle

Chen, D, Stegbauer, J, Sparks, MA, Kohan, D, Griffiths, R, Herrera, M, Gurley, S & Coffman, TM 2016, 'Impact of angiotensin type 1A receptors in principal cells of the collecting duct on blood pressure and hypertension', Hypertension, vol. 67, no. 6, pp. 1291-1297. https://doi.org/10.1161/HYPERTENSIONAHA.115.06987
Chen, Daian ; Stegbauer, Johannes ; Sparks, Matthew A. ; Kohan, Donald ; Griffiths, Robert ; Herrera, Marcela ; Gurley, Susan ; Coffman, Thomas M. / Impact of angiotensin type 1A receptors in principal cells of the collecting duct on blood pressure and hypertension. In: Hypertension. 2016 ; Vol. 67, No. 6. pp. 1291-1297.
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