Abstract 180: Downregulation of GRK2 by Long-Term Exercise Improves Vascular Insulin Sensitivity and Delays the Development of Hypertension in SHRs
Arteriosclerosis, Thrombosis, and Vascular Biology
Abstract
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.
Information & Authors
Information
Published In
Copyright
© 2014 by American Heart Association, Inc.
History
Published in print: May 2014
Published online: 17 March 2018
Key Words:
Authors
Metrics & Citations
Metrics
Citations
Download Citations
If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Select your manager software from the list below and click Download.
View Options
View options
PDF and All Supplements
Download PDF and All SupplementsLogin options
Check if you have access through your login credentials or your institution to get full access on this article.
Personal login Institutional LoginPurchase Options
Purchase this article to access the full text.
eLetters(0)
eLetters should relate to an article recently published in the journal and are not a forum for providing unpublished data. Comments are reviewed for appropriate use of tone and language. Comments are not peer-reviewed. Acceptable comments are posted to the journal website only. Comments are not published in an issue and are not indexed in PubMed. Comments should be no longer than 500 words and will only be posted online. References are limited to 10. Authors of the article cited in the comment will be invited to reply, as appropriate.
Comments and feedback on AHA/ASA Scientific Statements and Guidelines should be directed to the AHA/ASA Manuscript Oversight Committee via its Correspondence page.