Voluntary Wheel Running and Pacing-Induced Dysfunction in Hypertension

PURPOSE: We examined how voluntary wheel running in the female, spontaneously hypertensive rat (SHR) impacts myocardial tolerance to pacing stress and determined whether direct adenylyl cyclase agonism via forskolin infusion improved myocardial performance during pacing. METHODS: Twenty-five 16-week-old female Wistar Kyoto (WKY, n = 8) and SHR (n = 17) were utilized. Animals within the SHR group were randomly assigned to a sedentary (SHR-SED, n = 8) or a voluntary wheel running (SHR-WHL, n = 9) group. The SHR-WHL had free access to a running wheel 24 h/day. Resting heart rates and blood pressures were collected immediately prior to sacrifice utilizing a tail cuff apparatus. Left ventricular (LV) function was measured in a Langendorff, isovolumic preparation during pacing stress (8.5 Hz) and during pacing stress + forskolin (5 micromol/L). RESULTS: SHR-WHL showed cardiac enlargement without alterations in heart rate, systolic blood pressure, or rate-pressure product. Pacing stress impaired inotropic and lusitropic performance to a similar extent in all groups (p < 0.05), while forskolin infusion improved LV function to a similar extent in all groups (p < 0.05). CONCLUSIONS: These data suggest that voluntary wheel running in SHR does not protect from pacing-induced myocardial dysfunction, and adenylyl cyclase agonism during pacing stress can functionally protect the heart. These data reiterate the importance of a competent myocardial beta-adrenergic signaling cascade.