141887-34-5

Angiotensin AT ₁ receptor

A81988 (A-81988) is labeled with tritium to high specific activity (16 Ci/mmol) and radioligand binding assays performed in rat liver membranes. [ ³ H]A81988 binds with high affinity (K _D =0.57 nM) and the K _D determined from kinetics assays is similar. Non-specific binding (defined with 1 μM angiotensin-II) is very low (< 6% at the K _D ). The binding of [ ³ H]A81988 is competitive and exhibits appropriate pharmacological specificity for compounds acting at angiotensin AT ₁ receptors.

To verify this hypothesis, B ₂ ^-/- or wild-type mice (B ₂ ^+/+ ) are administered a nonpeptide antagonist of Ang II type 1 (AT ₁ ) receptors (A81988) from conception through 180 days of age. Untreated B ₂ ^+/+ and B ₂ ^-/- served as controls. Blood pressure (BP) and heart rate are monitored with the use of tail-cuff plethysmography at regular intervals. Ventricular weights, diameters, wall thickness, chamber volume, and myocardial fibrosis are measured at 40 and 180 days. No differences are observed in BP, heart rate, and cardiac weight and dimensions between treated and untreated B ₂ ^+/+ . The BP of AT ₁ antagonist-treated B ₂ ^-/- is reduced until 70 days; then, it increases to the levels found in untreated B ₂ ^-/- . AT ₁ receptor blockade results in a reduction in left ventricular mass, chamber volume, and wall thickness and abrogated myocardial fibrosis in B ₂ ^-/- . A81988 (A-81988) decreases the BP of Bk2r ^-/- either in normosodic conditions or after sodium deprivation, whereas in Bk2r ^+/+ it produces a modest decrease under hyposodic conditions only.