PMID- 30624974
OWN - NLM
STAT- MEDLINE
DCOM- 20191119
LR  - 20210811
IS  - 1522-1490 (Electronic)
IS  - 0363-6119 (Print)
IS  - 0363-6119 (Linking)
VI  - 316
IP  - 2
DP  - 2019 Feb 1
TI  - AT(1) receptors in the subfornical organ modulate arterial pressure and the 
      baroreflex in two-kidney, one-clip hypertensive rats.
PG  - R172-R185
LID - 10.1152/ajpregu.00289.2018 [doi]
AB  - The subfornical organ (SFO), a forebrain circumventricular organ that lies 
      outside the blood-brain barrier, has been implicated in arterial pressure and 
      baroreflex responses to angiotensin II (ANG II). We tested whether 
      pharmacological inhibition or selective silencing of SFO ANG II type 1 receptors 
      (AT(1)R) of two-kidney, one-clip rats with elevated plasma ANG II decreases 
      resting arterial pressure and renal sympathetic nerve activity (RSNA) and/or 
      modulates arterial baroreflex responses of heart rate (HR) and RSNA. Male 
      Sprague-Dawley rats underwent renal artery clipping [2-kidney, 1-clip (2K,1C)] or 
      sham clipping (sham). After 6 wk, conscious rats instrumented with vascular 
      catheters, renal nerve electrodes, and a cannula directed to the SFO were 
      studied. In another set of experiments, rats were instrumented with hemodynamic 
      and nerve radio transmitters and injected with scrambled RNA or silencing RNA 
      targeted against AT(1)R. Mean arterial pressure (MAP) was significantly higher in 
      2K,1C rats. Acute SFO injection with the AT(1)R inhibitor losartan did not change 
      MAP in sham or 2K,1C rats. Baroreflex curves of HR and RSNA were shifted 
      rightward in 2K,1C rats. Losartan exerted no effect. SFO AT(1)R knockdown did not 
      influence MAP in sham rats but decreased MAP in 2K,1C rats, despite no change in 
      plasma ANG II or resting RSNA. AT(1)R knockdown prevented the reduction in 
      maximum gain and slope of baroreflex responses of HR and RSNA; the reduced RSNA 
      response to baroreceptor unloading was partially restored in 2K,1C rats. These 
      findings show that AT(1)R activation within the SFO contributes to hypertension 
      and baroreflex dysfunction in 2K,1C rats and highlight the temporal requirement 
      for reversal of these effects.
FAU - Rossi, Noreen F
AU  - Rossi NF
AUID- ORCID: 0000-0002-5886-427X
AD  - Departments of Internal Medicine and Physiology, Wayne State University School of 
      Medicine , Detroit, Michigan.
AD  - John D. Dingell Veterans Administration Medical Center , Detroit, Michigan.
FAU - Zenner, Zachary
AU  - Zenner Z
AD  - Departments of Internal Medicine and Physiology, Wayne State University School of 
      Medicine , Detroit, Michigan.
FAU - Rishi, Arun K
AU  - Rishi AK
AD  - Department of Oncology, Wayne State University School of Medicine , Detroit, 
      Michigan.
AD  - John D. Dingell Veterans Administration Medical Center , Detroit, Michigan.
FAU - Levi, Edi
AU  - Levi E
AD  - Department of Pathology, Wayne State University School of Medicine , Detroit, 
      Michigan.
AD  - John D. Dingell Veterans Administration Medical Center , Detroit, Michigan.
FAU - Maliszewska-Scislo, Maria
AU  - Maliszewska-Scislo M
AD  - Departments of Internal Medicine and Physiology, Wayne State University School of 
      Medicine , Detroit, Michigan.
LA  - eng
GR  - I01 BX001164/BX/BLRD VA/United States
GR  - I01 RX000851/RX/RRD VA/United States
GR  - IK6 BX004015/BX/BLRD VA/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20190109
PL  - United States
TA  - Am J Physiol Regul Integr Comp Physiol
JT  - American journal of physiology. Regulatory, integrative and comparative 
      physiology
JID - 100901230
RN  - 0 (Receptor, Angiotensin, Type 1)
RN  - 11128-99-7 (Angiotensin II)
RN  - JMS50MPO89 (Losartan)
SB  - IM
MH  - Angiotensin II/pharmacology
MH  - Animals
MH  - Arterial Pressure/*drug effects
MH  - Baroreflex/*drug effects
MH  - Blood Pressure/physiology
MH  - Hemodynamics/drug effects
MH  - Hypertension/physiopathology
MH  - Losartan/*pharmacology
MH  - Male
MH  - Rats, Sprague-Dawley
MH  - Receptor, Angiotensin, Type 1/*drug effects
MH  - Renal Artery/physiopathology
MH  - Subfornical Organ/*drug effects
MH  - Surgical Instruments
PMC - PMC6397354
OTO - NOTNLM
OT  - Goldblatt kidney
OT  - angiotensin II
OT  - renal sympathetic nerve activity
COIS- No conflicts of interest, financial or otherwise, are declared by the authors.
EDAT- 2019/01/10 06:00
MHDA- 2019/11/20 06:00
PMCR- 2020/02/01
CRDT- 2019/01/10 06:00
PHST- 2019/01/10 06:00 [pubmed]
PHST- 2019/11/20 06:00 [medline]
PHST- 2019/01/10 06:00 [entrez]
PHST- 2020/02/01 00:00 [pmc-release]
AID - R-00289-2018 [pii]
AID - 10.1152/ajpregu.00289.2018 [doi]
PST - ppublish
SO  - Am J Physiol Regul Integr Comp Physiol. 2019 Feb 1;316(2):R172-R185. doi: 
      10.1152/ajpregu.00289.2018. Epub 2019 Jan 9.