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(R)-(-)-Phenylephrine is a selective α ₁ -adrenoceptor agonist with pK _i values of 5.86, 4.87 and 4.70 for α _1D , α _1B and α _1A receptors respectively. Phenylephrine promotes cardiac fibroblast proliferation. Phenylephrine activates CaN and evokes NFAT3 nuclear translocation. It suggests that the Ca( ²⁺ )/CaN/NFAT pathway mediates phenylephrine -induced cardiac fibroblast proliferation, and this pathway might be a possible therapeutic target in cardiac fibrosis.

Perfusion of hearts with 100 μM phenylephrine causes a rapid (maximal at 10 min) 12-fold activation of two p38-MAPK isoforms. α ₁ -adrenoceptor agonists such as phenylephrine increase the contractility of the heart. Phenylephrine also activates SAPKs/JNKs in neonatal ventricular myocytes. Phenylephrine could increase the alveolar fluid clearance in high tidal volume-ventilated rats and accelerate the absorption of pulmonary edema.