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Impact of Angiotensin Type 1A Receptors in Principal Cells of the Collecting Duct on Blood Pressure and Hypertension.

Publication ,  Journal Article
Chen, D; Stegbauer, J; Sparks, MA; Kohan, D; Griffiths, R; Herrera, M; Gurley, SB; Coffman, TM
Published in: Hypertension
June 2016

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.

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Published In

Hypertension

DOI

EISSN

1524-4563

Publication Date

June 2016

Volume

67

Issue

6

Start / End Page

1291 / 1297

Location

United States

Related Subject Headings

  • Renin-Angiotensin System
  • Reference Values
  • Receptor, Angiotensin, Type 1
  • Random Allocation
  • Mice
  • Kidney Tubules, Collecting
  • Hypertension
  • Disease Models, Animal
  • Cells, Cultured
  • Cardiovascular System & Hematology
 

Citation

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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
Chen, Daian, Johannes Stegbauer, Matthew A. Sparks, Donald Kohan, Robert Griffiths, Marcela Herrera, Susan B. Gurley, and Thomas M. Coffman. “Impact of Angiotensin Type 1A Receptors in Principal Cells of the Collecting Duct on Blood Pressure and Hypertension.Hypertension 67, no. 6 (June 2016): 1291–97. https://doi.org/10.1161/HYPERTENSIONAHA.115.06987.
Chen D, Stegbauer J, Sparks MA, Kohan D, Griffiths R, Herrera M, et al. Impact of Angiotensin Type 1A Receptors in Principal Cells of the Collecting Duct on Blood Pressure and Hypertension. Hypertension. 2016 Jun;67(6):1291–7.
Chen, Daian, et al. “Impact of Angiotensin Type 1A Receptors in Principal Cells of the Collecting Duct on Blood Pressure and Hypertension.Hypertension, vol. 67, no. 6, June 2016, pp. 1291–97. Pubmed, doi:10.1161/HYPERTENSIONAHA.115.06987.
Chen D, Stegbauer J, Sparks MA, Kohan D, Griffiths R, Herrera M, Gurley SB, Coffman TM. Impact of Angiotensin Type 1A Receptors in Principal Cells of the Collecting Duct on Blood Pressure and Hypertension. Hypertension. 2016 Jun;67(6):1291–1297.

Published In

Hypertension

DOI

EISSN

1524-4563

Publication Date

June 2016

Volume

67

Issue

6

Start / End Page

1291 / 1297

Location

United States

Related Subject Headings

  • Renin-Angiotensin System
  • Reference Values
  • Receptor, Angiotensin, Type 1
  • Random Allocation
  • Mice
  • Kidney Tubules, Collecting
  • Hypertension
  • Disease Models, Animal
  • Cells, Cultured
  • Cardiovascular System & Hematology