Developmental activity of the renin-angiotensin system during the "critical period" modulates later L-NAME-induced hypertension and renal injury

Kimiko Ishiguro, Hiroyuki Sasamura, Yusuke Sakamaki, Hiroshi Itoh, Takao Saruta

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

The incidence of hypertension and hypertensive renal disease is increasing worldwide, and new strategies to prevent these diseases need to be investigated. The aims of this study were 1) to examine if transient exposure to an angiotensin receptor blocker (ARB) during an early period in hypertension development confers protection against subsequent worsening of hypertension and renal injury induced by the NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME), and 2) conversely, to examine the effects of transient exposure to angiotensin II (Ang II) during the same period. First, spontaneously hypertensive rats (SHR) were treated transiently from age 3 to 10 weeks with ah ARB (candesartan cilexetil), a calcium channel antagonist or a vasodilator, then taken off treatment for 2 months. Administration of L-NAME at age 18 weeks caused severe hypertension and renal injury. However, the rats that had been exposed to the ARB not only had a lower blood pressure, but also failed to show signs of renal injury or increase of oxidetive stress. Furthermore, the elevation of components of the renin-angiotensin-aldosterone system was also suppressed in these rats. In the second study, Wistar-Kyoto rats (WKY) and SHR were exposed to Ang II from age 4 to 8 weeks. The follow-up showed that the blood pressures in the WKY remained elevated compared to controls, while the SHR had heightened increases in blood pressure, renal renin mRNA, and urinary 8-hyroxydeoxyguanosine after L-NAME administration. Together, these experiments demonstrate that transient treatment of rats during an early phase in the development of hypertension with an ARB suppresses the renin-angiotensin-aldosterone system and confere long-term protection against subsequent L-NAME-induced renal injury and increases in renal oxidative stress. Conversely, developmental exposure to Ang II during this "criticar" period had the opposite effect, predisposing rats to higher blood pressure, renal Injury, and oxidative stress after L-NAME administration.

Original languageEnglish
Pages (from-to)63-75
Number of pages13
JournalHypertension Research
Volume30
Issue number1
DOIs
Publication statusPublished - 2007 Jan

Fingerprint

Renal Hypertension
NG-Nitroarginine Methyl Ester
Renin-Angiotensin System
Angiotensin Receptor Antagonists
Kidney
Wounds and Injuries
Inbred SHR Rats
Inbred WKY Rats
Blood Pressure
Hypertension
Angiotensin II
Oxidative Stress
Calcium Channel Blockers
Vasodilator Agents
Renin
Nitric Oxide Synthase
Messenger RNA
Incidence

Keywords

  • Angiotensin
  • Hypertension
  • Oxidative stress
  • Renal injury
  • Renin-angiotensin-aldosterone system

ASJC Scopus subject areas

  • Internal Medicine

Cite this

Developmental activity of the renin-angiotensin system during the "critical period" modulates later L-NAME-induced hypertension and renal injury. / Ishiguro, Kimiko; Sasamura, Hiroyuki; Sakamaki, Yusuke; Itoh, Hiroshi; Saruta, Takao.

In: Hypertension Research, Vol. 30, No. 1, 01.2007, p. 63-75.

Research output: Contribution to journalArticle

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