Exaggerated blood pressure variability superimposed on hypertension aggravates cardiac remodeling in rats via angiotensin II system-mediated chronic inflammation

Hiroshi Kudo, Hisashi Kai, Hidemi Kajimoto, Mitsuhisa Koga, Narimasa Takayama, Takahiro Mori, Ayami Ikeda, Suguru Yasuoka, Takahiro Anegawa, Hiroharu Mifune, Seiya Kato, Yoshitaka Hirooka, Tsutomu Imaizumi

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Abstract

Hypertensive patients with large blood pressure variability (BPV) have aggravated end-organ damage. However, the pathogenesis remains unknown. We investigated whether exaggerated BPV aggravates hypertensive cardiac remodeling and function by activating inflammation and angiotensin II-mediated mechanisms. A model of exaggerated BPV superimposed on chronic hypertension was created by performing bilateral sinoaortic denervation (SAD) in spontaneously hypertensive rats (SHRs). SAD increased BPV to a similar extent in Wistar Kyoto rats and SHRs without significant changes in mean blood pressure. SAD aggravated left ventricular and myocyte hypertrophy and myocardial fibrosis to a greater extent and impaired left ventricular systolic function in SHRs. SAD induced monocyte chemoattractant protein-1, transforming growth factor-β, and angiotensinogen mRNA upregulations and macrophage infiltration of the heart in SHRs. The effects of SAD on cardiac remodeling and inflammation were much smaller in Wistar Kyoto rats compared with SHRs. Circulating levels of norepinephrine, the active form of renin, and inflammatory cytokines were not affected by SAD in Wistar Kyoto rats and SHRs. A subdepressor dose of candesartan abolished the SAD-induced left ventricular/myocyte hypertrophy, myocardial fibrosis, macrophage infiltration, and inductions of monocyte chemoattractant protein-1, transforming growth factor-β, and angiotensinogen and subsequently prevented systolic dysfunction in SHRs with SAD. These findings suggest that exaggerated BPV induces chronic myocardial inflammation and thereby aggravates cardiac remodeling and systolic function in hypertensive hearts. The cardiac angiotensin II system may play a role in the pathogenesis of cardiac remodeling and dysfunction induced by a combination of hypertension and exaggerated BPV.

Original languageEnglish
Pages (from-to)832-838
Number of pages7
JournalHypertension
Volume54
Issue number4
DOIs
Publication statusPublished - Oct 1 2009

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Denervation
Angiotensin II
Inbred SHR Rats
Blood Pressure
Hypertension
Inflammation
Inbred WKY Rats
Angiotensinogen
Chemokine CCL2
Transforming Growth Factors
Left Ventricular Hypertrophy
Muscle Cells
Fibrosis
Macrophages
Left Ventricular Function
Renin
Norepinephrine
Up-Regulation
Cytokines
Messenger RNA

All Science Journal Classification (ASJC) codes

  • Internal Medicine

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Exaggerated blood pressure variability superimposed on hypertension aggravates cardiac remodeling in rats via angiotensin II system-mediated chronic inflammation. / Kudo, Hiroshi; Kai, Hisashi; Kajimoto, Hidemi; Koga, Mitsuhisa; Takayama, Narimasa; Mori, Takahiro; Ikeda, Ayami; Yasuoka, Suguru; Anegawa, Takahiro; Mifune, Hiroharu; Kato, Seiya; Hirooka, Yoshitaka; Imaizumi, Tsutomu.

In: Hypertension, Vol. 54, No. 4, 01.10.2009, p. 832-838.

Research output: Contribution to journalArticle

Kudo, H, Kai, H, Kajimoto, H, Koga, M, Takayama, N, Mori, T, Ikeda, A, Yasuoka, S, Anegawa, T, Mifune, H, Kato, S, Hirooka, Y & Imaizumi, T 2009, 'Exaggerated blood pressure variability superimposed on hypertension aggravates cardiac remodeling in rats via angiotensin II system-mediated chronic inflammation', Hypertension, vol. 54, no. 4, pp. 832-838. https://doi.org/10.1161/HYPERTENSIONAHA.109.135905
Kudo, Hiroshi ; Kai, Hisashi ; Kajimoto, Hidemi ; Koga, Mitsuhisa ; Takayama, Narimasa ; Mori, Takahiro ; Ikeda, Ayami ; Yasuoka, Suguru ; Anegawa, Takahiro ; Mifune, Hiroharu ; Kato, Seiya ; Hirooka, Yoshitaka ; Imaizumi, Tsutomu. / Exaggerated blood pressure variability superimposed on hypertension aggravates cardiac remodeling in rats via angiotensin II system-mediated chronic inflammation. In: Hypertension. 2009 ; Vol. 54, No. 4. pp. 832-838.
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AU - Kato, Seiya

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