Korean J Physiol Pharmacol.  2020 Jan;24(1):53-68. 10.4196/kjpp.2020.24.1.53.

Interaction of genetic background and exercise training intensity on endothelial function in mouse aorta

• Kim SK
• Avila JJ
• Massett MP

• KMID: 2466570
• DOI: http://doi.org/10.4196/kjpp.2020.24.1.53

Abstract

The purpose of this study was to characterize the genetic contribution to endothelial adaptation to exercise training. Vasoreactivity was assessed in aortas from four inbred mouse strains (129S1, B6, NON, and SJL) after 4 weeks of moderate intensity continuous exercise training (MOD), high intensity interval training (HIT) or in sedentary controls (SED). Intrinsic variations in endothelium-dependent vasorelaxation (EDR) to acetylcholine (ACh) as well as vasocontractile responses were observed across SED groups. For responses to exercise training, there was a significant interaction between mouse strain and training intensity on EDR. Exercise training had no effect on EDR in aortas from 129S1 and B6 mice. In NON, EDR was improved in aortas from MOD and HIT compared with respective SED, accompanied by diminished responses to PE in those groups. Interestingly, EDR was impaired in aorta from SJL HIT compared with SED. The transcriptional activation of endothelial genes was also influenced by the interaction between mouse strain and training intensity. The number of genes altered by HIT was greater than MOD, and there was little overlap between genes altered by HIT and MOD. HIT was associated with gene pathways for inflammatory responses. NON MOD genes showed enrichment for vessel growth pathways. These findings indicate that exercise training has non-uniform effects on endothelial function and transcriptional activation of endothelial genes depending on the interaction between genetic background and training intensity.

Keyword

Endothelium; Exercise; Gene expression profiling; Inbred mouse strain

MeSH Terms

Acetylcholine
Animals
Aorta*
Endothelium
Gene Expression Profiling
Genetic Background*
Mice*
Mice, Inbred Strains
Transcriptional Activation
Vasodilation
Acetylcholine

Figure

• 

  Fig. 1 Effect of moderate-intensity continuous (MOD) and high-intensity interval training (HIT) on oxidative enzyme activity in gastrocnemius muscle from four inbred mouse strains. Eight-week old male mice (B6, 129S1, SJL, and NON) were trained with MOD or HIT for 4 weeks. (A) Responses of citrate synthase (CS) activity (nmol · min−1 · mg−1) to two training intensities. (B) Responses of succinate dehydrogenase (SDH) activity (nmol · min−1 · mg−1) to two exercise training intensities. Values are expressed as mean ± SE. n = 6 mice per group per strain. *p < 0.05 significantly different from sedentary controls (SED) within the same strain. †p < 0.05 significantly different from SED of B6.

• 

  Fig. 2 Differences in intrinsic vascular reactivity among sedentary mice from four inbred strains. Intrinsic vascular reactivity was assessed using cumulative concentration-response curves to four different vasoactive agents in aortas from sedentary mice (13-week old) of four inbred strains. (A) acetylcholine (ACh), (B) sodium nitroprusside (SNP), (C) phenylephrine (PE), and (D) potassium chloride (KCl). Cumulative concentration-response curves are expressed by percent relaxation or change in tension (%). Values are expressed as mean ± SE. n = 6 mice per strain. †p < 0.05 significantly different from sedentary controls (SED) of B6.

• 

  Fig. 3 Effect of moderate-intensity continuous (MOD) and high-intensity interval training (HIT) on acetylcholine-induced endothelium-dependent relaxation in aortas from four inbred mouse strains. After exercise training with moderate intensity continuous running training (MOD) or high intensity interval training (HIT) for 4 weeks, cumulative concentration-response curves to acetylcholine (ACh, 10−9 to 10−5 M) were assessed in isolated thoracic aortas from four inbred strains, (A) B6, (B) 129S1, (C) SJL, and (D) NON. Cumulative concentration-response curves are expressed by percent relaxation (%). Values are expressed as mean ± SE. n = 6 mice per group per strain. *p < 0.05 significantly different from sedentary controls (SED) within the same strain.

• 

  Fig. 4 Effect of moderate-intensity continuous (MOD) and high-intensity interval training (HIT) on sodium nitroprusside-induced endothelium-independent vasorelaxation in aortas from four inbred mouse strains. After exercise training with moderate intensity continuous running training (MOD) or high intensity interval training (HIT) for 4 weeks, cumulative concentration-response curves to sodium nitroprusside (SNP, 10−9 to 10−5 M) were assessed in isolated thoracic aortas from 4 inbred strains, (A) B6, (B) 129S1, (C) SJL, and (D) NON. Cumulative concentration-response curves are expressed by percent relaxation (%). Values are expressed as mean ± SE. n = 6 mice per group per strain. SNP-induced endothelium-independent vasorelaxation was not different among groups within any of strains.

• 

  Fig. 5 Effect of moderate-intensity continuous (MOD) and high-intensity interval training (HIT) on phenylephrine-induced contraction in aortas from four inbred mouse strains. After exercise training with moderate intensity continuous running training (MOD) or high intensity interval training (HIT) for 4 weeks, cumulative concentration-response curves to phenylephrine (PE, 10−9 to 10−5 M) were assessed in isolated thoracic aortas from four inbred strains, (A) B6, (B) 129S1, (C) SJL, and (D) NON. Cumulative concentration-response curves are expressed by change in tension (%). Values are expressed as mean ± SE. n = 6 mice per group per strain. *p < 0.05 significantly different from sedentary controls (SED) within the same strain.

• 

  Fig. 6 Effect of moderate-intensity continuous (MOD) and high-intensity interval training (HIT) on potassium chloride-induced contraction in aortas from four inbred mouse strains. After exercise training with moderate intensity continuous running training (MOD) or high intensity interval training (HIT) for 4 weeks, cumulative concentration-response curves to potassium chloride (KCl, 5–100 mM) were assessed in isolated thoracic aortas from four inbred strains, (A) B6, (B) 129S1, (C) SJL, and (D) NON. Cumulative concentration-response curves are expressed by change in tension (%). Values are expressed as mean ± SE. n = 6 mice per group per strain. KCl-induced contraction was not different among groups within any of strains.

• 

  Fig. 7 Effect of moderate-intensity continuous (MOD) and highintensity interval training (HIT) on nitrotyrosine level in gastrocnemius muscle from four inbred mouse strains. 8-week old male mice were trained with moderate intensity continuous running training (MOD) or high intensity interval training (HIT) for 4 weeks. Values are expressed as mean ± SE. n = 6 mice per group per strain. *p < 0.05 significantly different from sedentary controls (SED) within the same strain. †p < 0.05 significantly different from SED of B6.

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