Angiotensin II Type 1 Receptor Blocker Prevents Atrial Structural Remodeling in Rats with Hypertension Induced by Chronic Nitric Oxide Inhibition

Abstract

The prevalence of atrial fibrillation (AF) increases in patients with hypertension. Angiotensin II is involved in structural atrial remodeling, which contributes to the onset and maintenance of AF in paced animal models. We investigated the role of angiotensin II in atrial structural remodeling in rats with hypertension. Ten-week-old male Wistar-Kyoto rats were randomly divided into 4 groups: a control group (no treatment), an Nω-nitro-L-arginine methyl ester (L-NAME) group (administered L-NAME, an inhibitor of nitric oxide synthase, 1 g/l in drinking water), an L-NAME+candesartan group (L-NAME plus candesartan—an angiotensin II receptor blocker (ARB)—at 0.1 mg/kg/day), and an L-NAME+hydralazine group (L-NAME plus hydralazine at 120 mg/l in drinking water). Eight weeks after treatment, the L-NAME group showed significantly higher systolic blood pressure than the control group (197±12 vs.138±5 mmHg, p<0.05). Candesartan or hydralazine with L-NAME reduced systolic blood pressure to baseline. Chronic inhibition of NO synthesis increased the extent of fibrosis and transforming growth factor-β expression in atrial tissue, and both of these effects were prevented by candesartan, but not by hydralazine. Cardiac hypertrophy and dysfunction were induced in the L-NAME group, and these effects were also prevented by candesartan, but not by hydralazine. In contrast, the decrease in thrombomodulin expression in the atrial endocardium in hypertensive rats was restored by candesartan and hydralazine. The ARB prevented atrial structural remodeling, a possible contributing factor for the development of AF, in the hearts of rats with hypertension induced by long-term inhibition of NO synthesis.

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Correspondence to Tetsuo Minamino.

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Okazaki, H., Minamino, T., Tsukamoto, O. et al. Angiotensin II Type 1 Receptor Blocker Prevents Atrial Structural Remodeling in Rats with Hypertension Induced by Chronic Nitric Oxide Inhibition. Hypertens Res 29, 277–284 (2006). https://doi.org/10.1291/hypres.29.277

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Keywords

  • angiotensin II type 1 receptor blocker
  • atrial fibrillation
  • nitric oxide
  • hypertension
  • atrial remodeling

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