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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.