title: Healthy older humans exhibit augmented carotid-cardiac baroreflex sensitivity with aspirin during muscle mechanoreflex and metaboreflex activation.
abstract: Low-dose aspirin inhibits thromboxane production and augments the sensitivity of carotid baroreflex (CBR) control of heart rate (HR) during concurrent muscle mechanoreflex and metaboreflex activation in healthy young humans. However, it is unknown how aging affects this response. Therefore, the effect of low-dose aspirin on carotid-cardiac baroreflex sensitivity during muscle mechanoreflex with and without metaboreflex activation in healthy older humans was examined. Twelve older subjects (6 men and 6 women, mean age: 62 ± 1 yr) performed two trials during two visits preceded by 7 days of low-dose aspirin (81 mg) or placebo. One trial involved 3 min of passive calf stretch (mechanoreflex) during 7.5 min of limb circulatory occlusion (CO). In another trial, CO was preceded by 1.5 min of 70% maximal voluntary contraction isometric calf exercise (mechanoreflex and metaboreflex). HR (ECG) and mean arterial blood pressure (MAP; Finometer) were recorded. CBR function was assessed using rapid neck pressure application (+40 to -80 mmHg). Aspirin significantly decreased baseline thromboxane B2 production by 83 ± 4% (P < 0.05) but did not affect 6-keto-PGF1α. After aspirin, CBR-HR maximal gain and operating point gain were significantly higher during stretch with metabolite accumulation compared with placebo (maximal gain: -0.23 ± 0.03 vs. -0.14 ± 0.02 and operating point gain: -0.11 ± 0.03 vs. -0.04 ± 0.01 beats·min(-1)·mmHg(-1) for aspirin and placebo, respectively, P < 0.05). In conclusion, these findings suggest that low-dose aspirin augments CBR-HR sensitivity during concurrent muscle mechanoreflex and metaboreflex activation in healthy older humans. This increased sensitivity appears linked to reduced thromboxane sensitization of muscle mechanoreceptors, which consequently improves CBR-HR control.
authors.affiliation: Penn State Hershey Heart and Vascular Institute, Pennsylvania State University College of Medicine and Milton S. Hershey Medical Center, Hershey, Pennsylvania; and rdrew1@hmc.psu.edu.
authors.forename: Rachel C
authors.identifier: http://orcid.org/0000-0001-8001-1946
authors.initials: RC
authors.lastname: Drew
authors.affiliation: Penn State Hershey Heart and Vascular Institute, Pennsylvania State University College of Medicine and Milton S. Hershey Medical Center, Hershey, Pennsylvania; and.
authors.forename: Cheryl A
authors.initials: CA
authors.lastname: Blaha
authors.affiliation: Penn State Hershey Heart and Vascular Institute, Pennsylvania State University College of Medicine and Milton S. Hershey Medical Center, Hershey, Pennsylvania; and.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Herr
authors.affiliation: Penn State Hershey Cellular and Molecular Physiology, Pennsylvania State University College of Medicine and Milton S. Hershey Medical Center, Hershey, Pennsylvania.
authors.forename: Sean D
authors.initials: SD
authors.lastname: Stocker
authors.affiliation: Penn State Hershey Heart and Vascular Institute, Pennsylvania State University College of Medicine and Milton S. Hershey Medical Center, Hershey, Pennsylvania; and.
authors.forename: Lawrence I
authors.initials: LI
authors.lastname: Sinoway
mesh_terms: D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D000367:Age Factors; D001241:Aspirin / Q000008:administration & dosage*; D017704:Baroreflex / Q000187:drug effects*; D001794:Blood Pressure / Q000187:drug effects; D002628:Chemoreceptor Cells / Q000187:drug effects* / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage*; D005260:Female; D064368:Healthy Volunteers; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D035002:Lower Extremity; D008297:Male; D008465:Mechanoreceptors / Q000187:drug effects* / Q000378:metabolism; D040542:Mechanotransduction, Cellular / Q000187:drug effects*; D008875:Middle Aged; D009119:Muscle Contraction; D018482:Muscle, Skeletal / Q000294:innervation* / Q000378:metabolism; D013929:Thromboxane B2 / Q000097:blood
chemical_list: D016861:Cyclooxygenase Inhibitors; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D001241:Aspirin
keywords: age; aspirin; baroreflex; mechanoreflex; thromboxane