PURPOSE: Inflammation may contribute to the pathogenesis of specific @entity65 , but it is uncertain if mediators released during the inflammatory process will affect the continued efficacy of drugs used to treat clinical signs of the @entity299 . We investigated the role of the complement 5a receptor 1 ( @entity47513 / @entity47513 ) in the cardiac response to @entity32 or @entity2165 , and the effect of @entity47513 deletion in control of baseline heart rate in an anesthetized @entity19 model. METHODS: An initial study showed that @entity54483 , an antagonist of @entity47513 in normal C57BL6/J (wild type, @entity7097 ) @entity19 reduced heart rate (HR) and appeared to have a protective effect on the heart following induced @entity295 . @entity47513 knockout ( @entity47513 -/-) @entity19 had a lower HR than wild type @entity19 , even during sham surgery. A model to assess heart rate variability (HRV) in anesthetized @entity19 was developed to assess the effects of inhibiting the b1-adrenoreceptor (b1-AR) in a randomized crossover study design. RESULTS: HR and LF Norm were constitutively lower and SDNN and HF Norm constitutively higher in the @entity47513 -/- compared with @entity7097 @entity19 (P< 0.001 for all outcomes). Administration of @entity2165 (2.5 mg/kg) reduced the HR and increased HRV (P< 0.05, respectively) in the wild type but not in the @entity47513 -/- @entity19 . There was no shift of the sympathovagal balance post- @entity2165 in either strains of @entity19 (P> 0.05), except for the reduced LF/HF (Lower frequency/High frequency) ratio (P< 0.05) at 60 min post- @entity2165 , suggesting increased parasympathetic tone of the heart due to the effect of @entity2165 administration. The HR of the @entity7097 @entity19 were lower post @entity2165 compared to the @entity47513 -/- @entity19 (P = 0.001) but the HRV of @entity47513 -/- @entity19 were significantly increased (P< 0.05), compared with @entity7097 @entity19 . CONCLUSION: Knockout of the @entity47513 attenuated the effect of b1-AR in the heart, suggesting an association between the b1-AR and @entity47513 , although further investigation is required to determine if this is a direct or causal association.

A Potential Link between the C5a Receptor 1 and the b1-Adrenoreceptor in the XXXX Heart.

@entity32 :: ('MESH:D007249', 'Disease') :: ['inflammation'] @entity54483 :: ('MESH:C438957', 'Chemical') :: ['PMX53'] @entity295 :: ('MESH:D018805', 'Disease') :: ['sepsis'] @entity47513 :: ('12273(Tax:10090)', 'Gene') :: ['C5aR1', 'CD88'] @entity19 :: ('10090', 'Species') :: ['mice', 'mouse'] @entity7097 :: ('MESH:C536751', 'Disease') :: ['WT'] @entity299 :: ('MESH:D006331', 'Disease') :: ['cardiac disease'] @entity2165 :: ('MESH:D001262', 'Chemical') :: ['atenolol'] @entity65 :: ('MESH:D002318', 'Disease') :: ['cardiovascular diseases']
@entity19 :: (10090,Species) :: ['Mouse']
