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Figure 5 Hypothetical mechanism of action of AT1-ant in heart failure: 1) AT1-ant prevent the effect of angiotensin II on the AT1 receptor, leading to cardioprotection (preventing cardiac hypertrophy, fibrosis, and remodeling and improving function); 2) angiotensin II activates the AT2 receptors, which act via release of kinins, and B2 and/or B1 receptors, which act via release of nitric oxide, thereby leading to anticardiac fibrosis, preventing remodeling and improving function; a) in BN rats with HF, B2-ant only blocks the B2 receptor; the B1 receptors may be activated and prevent cardiac hypertrophy; and b) in BNK rats neither B1 nor B2 receptors are activated; as circulating kinins are absent in this strain, and AT2 receptors may act directly via nitric oxide to prevent cardiac hypertrophy. Rectangular callouts (AT1-ant, AT2-ant or B2-ant) point to the receptor blockade site, and oval callouts point to two strains (BN and BNK). Abbreviations as in Figure 1.
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