Dual A1/A2B Receptor Blockade Improves Cardiac and Renal Outcomes in a @entity35 Model of XXXX with Preserved Ejection Fraction.

@entity407 @entity1 @entity2011 @entity712 @entity859 @entity35 @entity28 @entity6 @entity384 @entity1674 @entity628 @entity2299 @entity4683 @entity194 @entity299 @entity209 @entity413 @entity165 @entity72447
UNASSIGNED: @entity712 with preserved ejection fraction (HFpEF) is prevalent and often accompanied by the @entity209 . Current treatment options are limited. Here we test the hypothesis that combined A1/A2B @entity859 receptor blockade is beneficial in obese ZSF1 @entity35 , an animal model of HFpEF with the @entity209 . @entity72447 , a combined A1/A2B receptor antagonist, was administered orally (10 mg/kg/day) to obese ZSF1 @entity35 (n=10) for 24 weeks (from 20 to 44 weeks-of-age). Untreated ZSF1 @entity35 (n=9) served as controls. After 24 weeks of administration, @entity72447 significantly lowered plasma @entity1674 (mg/dL: Control Group, 4351    550; @entity72447 Group, 2900    551) without adversely affecting plasma @entity165 or activating renin release. @entity72447 significantly decreased 24-hour urinary @entity413 excretion (mg/kg/day: Control Group, 823    179; @entity72447 Group, 196    80) and improved oral @entity413 tolerance, @entity4683 , and @entity2011 . @entity72447 significantly augmented left ventricular diastolic function in association with a @entity299 and @entity299 . @entity72447 significantly reduced 24-hour urinary protein excretion (mg/kg/day: Control Group, 1702    263; @entity72447 Group, 1076    238), and this was associated with a reduction in @entity628 , @entity194 , @entity384 , and deposition of proteinaceous material in the tubules. These findings show that in a model of HFpEF with the @entity209 , A1/A2B receptor inhibition improves @entity407 , exerts antidiabetic actions, reduces HFpEF, improves cardiac histopathology, and affords renal protection. We conclude that chronic administration of combined A1/A2B receptor antagonists could be beneficial in @entity1 with HFpEF, particularly those with comorbidities such as @entity28 , @entity6 , and @entity2299 .
