Exercise Training Increases Beta Adrenergic Responsiveness In Hypertension

Abstract

Cardiac responses to beta-adrenergic receptor (BAR) stimulation are depressed in chronic hypertension. We tested whether exercise training (ET) could improve BAR responsiveness in spontaneous hypertensive rats (SHR) and whether BAR kinase (GRK2) plays a role after exercise in SHR. Methods Female, SHR (age: 4mo) were placed into a treadmill running (SHR-TRD, n=12; 20m/min, 1hr/day, 5d/wk, 12 wks) or sedentary group (SHR-SED, n=12). Age-matched WKY rats (n=12) were controls. Tail cuff systolic and diastolic blood pressures were determined. Isovolumic, Langendorff performance was measured (4.5 Hz, LVEDP = 12mmHg, coronary flow=16 ml/min, 2mM Ca2+). Following baseline, 5-minute infusions of isoproterenol (ISO) were administered (10−10 - 10−7 mol/L). Western blot analysis, myocardial morphometry, and histomorphometry were performed. Results Mean blood pressure was higher in SHR vs. WKY (P < 0.05) and unaltered with ET. Myocardial wall thickness and cell surface area were greater in SHR than WKY (P < 0.05) and augmented with exercise training (P < 0.05). At baseline, LV developed pressure (LVDevP) was greater in SHR vs. WKY (WKY: 154 ± 23; SHR-SED: 173 ± 10; SHR-TRD: 175 ± 5 mmHg). The peak response to ISO was shifted rightward 100-fold in both SHR groups relative to WKY. The peak ISO LVDevP response was similar between WKY and SHR-TRD, while the peak response of SHR-SED was blunted (WKY: 38 ± 11%; SHR-SED: 19 ± 9%; SHR-TRD: 49 ± 7%, P < 0.05) (Figure 1A). L type Ca2+ channel (LTCC) and the Na+/Ca2+ exchanger (NCX) abundance were increased in both SHR groups. Training increased ryanodine phosphorylation (RyRp) with no difference in ryanodine receptor density (RyRt) among groups. GRK2 levels were increased in SHR-SED vs. SHR-TRD relative to WKY (SED: 97.65 ± 38%; TRD: 17.53 ± 19%, P < 0.05) (Figure 1B.).Figure 1AFigure 1BConclusion BAR responsiveness is improved with exercise training in SHR, an effect at least in part, secondary to a downregulation of GRK2. Supported by the American Heart Association, Mid-Atlantic Affiliate (JRL), and the National Institute of Health SRH (HL33921) and WJK (HL61690 and HL56205).