Sex-Specific Differences in β-Adrenoceptor Signal Transduction in Heart Failure Due to Volume-Overload

Volume-overload upon inducing arteriovenous shunt was found to produce sex-dependent changes in cardiac hypertrophy and heart failure. These alterations are accompanied by sex-dependent changes in β-adrenoceptor (AR)—guanine protein—adenylyl cyclase complex in the heart. Unlike females, prolonged exposure of animals to volume-overload resulted in heart failure in males. Protein content of β1-AR and β2-AR as well as their mRNA levels in the heart were lower in males and higher in females upon inducing volume-overload. Hearts from females also showed higher adenylyl cyclase protein content as well as epinephrine stimulated adenylyl cyclase activity in comparison to male hearts subjected to volume-overload. Marked increase in β1-AR, β2-AR and adenylyl cyclase content and depression in epinephrine-stimulated adenylyl cyclase activity as well as plasma catecholamines, were seen due to ovariectomy. All these changes except those in plasma catecholamines were fully or partially prevented upon treatment of ovariectomized animals with estrogen. These sex-specific alterations in β-AR signal transduction system may explain the reduced risk of heart failure in females, unlike males, under stressful conditions.