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Jun, 2009

Blockade of angiotensin II type-1 receptor increases salt sensitivity in Sprague-Dawley rats

HYPERTENSION RESEARCH
  • Satoshi Endo
  • ,
  • Takefumi Mori
  • ,
  • Yoshimi Yoneki
  • ,
  • Takashi Nakamichi
  • ,
  • Takuma Hosoya
  • ,
  • Susumu Ogawa
  • ,
  • Goro Tokudome
  • ,
  • Tatsuo Hosoya
  • ,
  • Toshio Miyata
  • ,
  • Sadayoshi Ito

Volume
32
Number
6
First page
513
Last page
519
Language
English
Publishing type
DOI
10.1038/hr.2009.40
Publisher
NATURE PUBLISHING GROUP

This study determined the role of angiotensin II type-1 (AT1) receptor in the salt sensitivity of blood pressure. The mean arterial blood pressure (MAP) of Sprague-Dawley rats was monitored by radio telemetry and, after baseline measurements, rats were treated either with (1) vehicle, (2) AT1 receptor blocker (ARB) olmesartan (OLM, 100 nmol kg(-1) h(-1), subcutaneously), (3) OLM with hydrochlorothiazide (HCTZ, 40 mg kg(-1) day(-1), orally), (4) angiotensin II (AngII, 100 ng kg(-1) min(-1), subcutaneously) or with (5) AngII with OLM. Rats were fed a 0.5% salt diet during the baseline and first 7 days of treatment period, and the diet was then switched to one containing 8% salt for another 7 days. Urinary samples were collected in a metabolic cage at the end of each period. MAP of the vehicle group did not change throughout the study. In AngII-infused rats, BP increased only when rats were fed an 8% salt diet. OLM and OLM with AngII significantly reduced MAP when rats were on a 0.5% salt diet, but not on an 8% salt diet, indicating an enhanced salt sensitivity by OLM. Co-treatment with HCTZ reduced the salt sensitivity of OLM. The urinary level of the oxidative stress marker was increased by an 8% salt diet and was not altered by either OLM alone or in combination with HCTZ. However, OLM attenuated the salt-induced renal NAD(P) H (nicotinamide adenine dinucleotide phosphate) oxidase activity. These results indicate that AT1 receptor blockade increases salt sensitivity, which is reversed by diuretics. We conclude that OLM and HCTZ could be a useful combination for reduction of blood pressure even under high salt intake without changes in urinary oxidative stress levels. Hypertension Research (2009) 32, 513-519; doi: 10.1038/hr.2009.40; published online 1 May 2009

Link information
DOI
https://doi.org/10.1038/hr.2009.40
CiNii Articles
http://ci.nii.ac.jp/naid/10024831346
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000266628200016&DestApp=WOS_CPL
ID information
  • DOI : 10.1038/hr.2009.40
  • ISSN : 0916-9636
  • CiNii Articles ID : 10024831346
  • Web of Science ID : WOS:000266628200016

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