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2016 ; 67
(6
): 1291-7
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Impact of Angiotensin Type 1A Receptors in Principal Cells of the Collecting Duct
on Blood Pressure and Hypertension
#MMPMID27141055
Chen D
; Stegbauer J
; Sparks MA
; Kohan D
; Griffiths R
; Herrera M
; Gurley SB
; Coffman TM
Hypertension
2016[Jun]; 67
(6
): 1291-7
PMID27141055
show ga
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.