Low-Salt Diet and Circadian Dysfunction Synergize to Induce Angiotensin II-Dependent Hypertension in Mice

Paramita Pati, David J Fulton, Zsolt Bagi, Feng Chen, Yusi Wang, Julia Kitchens, Lisa A. Cassis, David W Stepp, Radu Daniel Rudic

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Blood pressure exhibits a robust circadian rhythm in health. In hypertension, sleep apnea, and even shift work, this balanced rhythm is perturbed via elevations in night-time blood pressure, inflicting silent damage to the vasculature and body organs. Herein, we examined the influence of circadian dysfunction during experimental hypertension in mice. Using radiotelemetry to measure ambulatory blood pressure and activity, the effects of angiotensin II administration were studied in wild-type (WT) and period isoform knockout (KO) mice (Per2-KO, Per2, 3-KO, and Per1, 2, 3-KO/Per triple KO [TKO] mice). On a normal diet, administration of angiotensin II caused nondipping blood pressure and exacerbated vascular hypertrophy in the Period isoform KO mice relative to WT mice. To study the endogenous effects of angiotensin II stimulation, we then administered a low-salt diet to the mice, which does stimulate endogenous angiotensin II in addition to lowering blood pressure. A low-salt diet decreased blood pressure in wild-type mice. In contrast, Period isoform KO mice lost their circadian rhythm in blood pressure on a low-salt diet, because of an increase in resting blood pressure, which was restorable to rhythmicity by the angiotensin receptor blocker losartan. Chronic administration of low salt caused vascular hypertrophy in Period isoform KO mice, which also exhibited increased renin levels and altered angiotensin 1 receptor expression. These data suggest that circadian clock genes may act to inhibit or control renin/angiotensin signaling. Moreover, circadian disorders such as sleep apnea and shift work may alter the homeostatic responses to sodium restriction to potentially influence nocturnal hypertension.

Original languageEnglish (US)
Pages (from-to)661-668
Number of pages8
JournalHypertension
Volume67
Issue number3
DOIs
StatePublished - Mar 1 2016

Fingerprint

Sodium-Restricted Diet
Angiotensin II
Blood Pressure
Hypertension
Knockout Mice
Protein Isoforms
Sleep Apnea Syndromes
Circadian Rhythm
Renin
Hypertrophy
Blood Vessels
Circadian Clocks
Angiotensin Receptors
Losartan
Angiotensin Receptor Antagonists
Angiotensins
Periodicity
Salts
Sodium
Diet

Keywords

  • aging
  • angiotensin
  • circadian
  • hypertension
  • hypertrophy
  • renin
  • sodium

ASJC Scopus subject areas

  • Internal Medicine

Cite this

Low-Salt Diet and Circadian Dysfunction Synergize to Induce Angiotensin II-Dependent Hypertension in Mice. / Pati, Paramita; Fulton, David J; Bagi, Zsolt; Chen, Feng; Wang, Yusi; Kitchens, Julia; Cassis, Lisa A.; Stepp, David W; Rudic, Radu Daniel.

In: Hypertension, Vol. 67, No. 3, 01.03.2016, p. 661-668.

Research output: Contribution to journalArticle

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