Mechanical stretch stimuli alter the morphology and function of cultured endothelial cells; however, little is known about the effects of daily muscle stretching on adaptations of endothelial function and muscle blood flow. The present study aimed to determine the effects of daily muscle stretching on endothelium-dependent vasodilatation and muscle blood flow in aged rats. The lower hindlimb muscles of aged Fischer rats were passively stretched by placing an ankle dorsiflexion splint for 30 min day , 5 days week , for 4 weeks. Blood flow to the stretched limb and the non-stretched contralateral limb was determined at rest and during treadmill exercise. Endothelium-dependent/independent vasodilatation was evaluated in soleus muscle arterioles. Levels of hypoxia-induced factor-1α, vascular endothelial growth factor A and neuronal nitric oxide synthase were determined in soleus muscle fibres. Levels of endothelial nitric oxide synthase and superoxide dismutase were determined in soleus muscle arterioles, and microvascular volume and capillarity were evaluated by microcomputed tomography and lectin staining, respectively. During exercise, blood flow to plantar flexor muscles was significantly higher in the stretched limb. Endothelium-dependent vasodilatation was enhanced in arterioles from the soleus muscle from the stretched limb. Microvascular volume, number of capillaries per muscle fibre, and levels of hypoxia-induced factor-1α, vascular endothelial growth factor and endothelial nitric oxide synthase were significantly higher in the stretched limb. These results indicate that daily passive stretching of muscle enhances endothelium-dependent vasodilatation and induces angiogenesis. These microvascular adaptations may contribute to increased muscle blood flow during exercise in muscles that have undergone daily passive stretch.

The risk for diastolic dysfunction increases with advancing age. Regular exercise training ameliorates age-related diastolic dysfunction; however, the underlying mechanisms have not been identified. We investigated whether (1) microvascular dysfunction contributes to the development of age-related diastolic dysfunction, and (2) initiation of late-life exercise training reverses age-related diastolic and microvascular dysfunction. Young and old rats underwent 10 weeks of exercise training or remained as sedentary, cage-controls. Isovolumic relaxation time (IVRT), early diastolic filling (E/A), myocardial performance index (MPI) and aortic stiffness (pulse wave velocity; PWV) were evaluated before and after exercise training or cage confinement. Coronary blood flow and vasodilatory responses of coronary arterioles were evaluated in all groups at the end of training. In aged sedentary rats, compared to young sedentary rats, a 42% increase in IVRT, a 64% decrease in E/A, and increased aortic stiffness (PWV: 6.36 ± 0.47 vs.4.89 ± 0.41, OSED vs. YSED, P < 0.05) was accompanied by impaired coronary blood flow at rest and during exercise. Endothelium-dependent vasodilatation was impaired in coronary arterioles from aged rats (maximal relaxation to bradykinin: 56.4 ± 5.1% vs. 75.3 ± 5.2%, OSED vs. YSED, P < 0.05). After exercise training, IVRT, a measure of active ventricular relaxation, did not differ between old and young rats. In old rats, exercise training reversed the reduction in E/A, reduced aortic stiffness, and eliminated impairment of coronary blood flow responses and endothelium-dependent vasodilatation. Thus, age-related diastolic and microvascular dysfunction are reversed by late-life exercise training. The restorative effect of exercise training on coronary microvascular function may result from improved endothelial function.

No abstract

We have previously reported that in old rats, reversal of age‐related vascular dysfunction by exercise training correlates with an increase in circulating adiponectin and its signaling within coronary vascular smooth muscle. In the current study, we investigated the effect of deletion of adiponectin on exercise training‐induced vascular adiponectin. C57BL/6 wild‐type (WT) or homozygous adiponectin knockout (AdipoKO) mice were obtained at 10–12 wks of age and underwent treadmill exercise training (EX) (12 m/min, 5° incline, 1 hr/day, 5 days/wk for 8 wks) or remained sedentary (SED) in cages. Arterioles isolated from cardiac and soleus muscle were assessed for contractile and vasodilatory function, and capillarity of the soleus muscle was evaluated. Exercise training increased flow‐induced dilation significantly in coronary arterioles of WT mice (P<0.01 EX vs. SED), but decreased flow‐induced dilation in coronary arterioles from AdipoKO mice. ACh‐induced dilation was reduced in coronary arterioles from AdipoKO mice as compared to those from WT mice (P<0.05 AdipoKO vs. WT). Exercise training reduced ACh‐induced dilation in arterioles from WT mice, but increased ACh‐induced dilation in arterioles from AdipoKO mice. Baseline capillarity increased in the soleus muscle of AdipoKO mice as compared to WT mice, but an exercise training‐induced increase in capillarity, detected in WT mice, was absent in AdipoKO mice. Contractile responsiveness to phenylephrine was increased in arterioles from the soleus muscle of both WT and AdipoKO mice (P<0.01 EX vs. SED in both WT and AdipoKO). These data indicate that adiponectin is a critical contributor to exercise training‐induced vascular adaptations; however, locally produced adiponectin may be more critical than circulating adiponectin in mediating these adaptations.Support or Funding InformationFlorida State University College of MedicineThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Circulating adiponectin levels have been shown to correlate with microvascular coronary function, suggesting a cardioprotective effect. Our previous work has shown that adiponectin deficiency decreases coronary smooth muscle contractile function and physiological cardiac hypertrophy that is not reversed with exercise training. However, it is unknown if adiponectin deficiency adversely affects endothelial‐dependent coronary vasodilation, leading to cardiac abnormalities. We tested the hypotheses that adiponectin is necessary for acetylcholine (ACh) and flow‐induced vasodilation in coronary arterioles. It was also hypothesized that exercise training would improve cardiac function in exercise trained wild‐type, but not adiponectin knock‐out (AdipoKO) mice.MethodsC57BL/6 wild‐type (WT) or homozygous AdipoKO mice were obtained at 10 weeks of age and underwent treadmill exercise (12 m/min, 5° incline, 1 hour/day, 5 days/week for 8 weeks) or remained sedentary in cages. At the end of the training/sedentary period, coronary resistance arterioles (intraluminal diameter <150 mm) were isolated, cannulated, and placed under an inverted microscope equipped with a video camera and caliper to record luminal diameter. Vasodilatory responses to ACh (1e‐9 to 1e–4M) and changes in flow (Pressure differences = 2–60 cm H2O) were then assessed. Pre/post cardiac function was measured with a high‐resolution imaging system (Vevo 2100), with M‐mode, and was used to assess ejection fraction, fractional shortening, and left ventricular (LV) mass. Pulsed‐wave Doppler was used to calculate isovolumic relaxation (IVRT)/contraction (IVCT) time.Resultsexercise‐trained WT mice demonstrated physiological cardiac hypertrophy, indicated by a significant increase in LV mass (P<0.05). Exercise‐trained WT mice also had a significantly greater ejection fraction and fractional shortening (both; p<0.05). In contrast, cardiac hypertrophy was absent in exercise‐trained AdipoKO mice and a significant decrease in ejection fraction and fractional shortening was found (both; p>0.05). Further, both sedentary groups were shown to have significant declines in fractional shortening and ejection fraction (p<0.05). Exercise‐training maintained both IVRT/IVCT in the WT mice; however, a significant (p<0.05) lengthening of the IVRT/IVCT was shown in exercise‐trained AdipoKO and WT sedentary mice (p<0.05). The sedentary AdipoKO was shown to have an increase in IVRT only (p<0.05). Sedentary WT mice had significantly greater mean vasodilation to ACh compared to sedentary AdipoKO (p<0.01). Exercise‐training led to increased flow‐induced dilation in the WT (p<0.05), but not the AdipoKO mice (p>0.05).Conclusionthese results indicate that adiponectin is necessary for improvements in cardiac function during exercise training in young adult mice. Additionally, adiponectin may help with preserved cardiac function and that flow‐induced coronary arteriolar vasodilation may have contributed to this response.Support or Funding InformationFSU Research FundsThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.