Abstract 180: Downregulation of GRK2 by Long-Term Exercise Improves Vascular Insulin Sensitivity and Delays the Development of Hypertension in SHRs
Aims: Exercise training, a recommended nonpharmacological strategy for hypertensive patients, exerts beneficial effect on blood pressure modulation, but the underlying mechanisms remain elusive. Vascular insulin resistance is an early pathologic alteration in hypertensive vascular injury and plays a critical role in the development of hypertension. This study aimed to investigate whether long-term physical exercise starting at prehypertensive period prevents the development of hypertension via improving vascular insulin sensitivity.
Methods: Young (4-week-old) prehypertensive spontaneously hypertensive rats (SHRs) and their normotensive Wistar-Kyoto controls (WKY) were subjected to a 10-week free-of-loading swim training session (60 min/day, 5 days/week). Insulin-induced mesenteric arteriolar vasorelaxation were determined.
Results: SHRs showed higher systolic blood pressure (SBP) and decreased insulin sensitivity of the whole body and resistance vessels compared with those of WKY rats. SBP in the exercised SHRs was significantly lower than that in sedentary ones (180.2±5.1 vs. 205.7±3.7 mmHg, n=6, P<0.05). Vascular insulin sensitivity in mesenteric arteries was improved after exercise training as evidenced by increased vasodilation response to insulin (29.0%±2.5% vs. 18.4%±5.9% to 1 μmol/L insulin, n=6, P<0.05). In addition, exercise downregulated vascular GRK2 expression and activity, which further increased insulin-stimulated vascular Akt/eNOS activation in exercised SHRs. More importantly, suppression of GRK2 with siRNA mimicked the effect of exercise-enhanced vascular insulin sensitivity, while upregulation of GRK2 by Chariot-mediated delivery reversed the exercise-induced vascular insulin sensitization.
Conclusions: Long-term regular physical exercise beginning at prehypertensive stage improves vascular insulin sensitivity via downregulating GRK2 and consequently delays the development of hypertension.
Author Disclosures: H. Zhang: None. W. Xing: None. F. Gao: None.
- © 2014 by American Heart Association, Inc.