English abstract
Background: Inactive lifestyle leads to a number of cardiovascular disorders many of which can be reversed by exercise training (ET). However, the underlying mechanisms are not fully understood. Important mechanisms reported in metabolically active
vasculatures such as coronary arteries during exercise involve increased function of vascular K+ channels and of endothelium dependent relaxations. However, data available on effect of ET on vasculature that constricts to acute exercise is scarce and
not conclusive. This study hypothesized that moderate intensity ET will result in adaptations of mesenteric arteries towards more vasoconstrive or/and less vasodilative abilities and large-conductance calcium-activated potassium channels (BKCa) would
play a role in these adaptations.
Objectives: To study the effect of ten weeks moderate intensity ET on the vasoreactivity of small and large mesenteric arteries and the functional contribution of BKCa channels on its arterial tone. Additionally, to compare the level of protein
expression of BKCa channels (α) and (β) subunits and of endothelial nitric oxide synthase (eNOS) in arteries isolated from sedentary (SED) and exercise (EXE) rats.
Methods: Young Fischer 344 rats (12 weeks old) were randomly assigned to sedentary (SED, n=24) or exercise trained group (EXE, n=28). The EXE rats underwent a progressive treadmill ET programme for 60 min/day, 5 days/ week for 10 weeks. Small
(diameter = 250.5±5.1μm) and large (diameter = 417.5±13.7μm) mesenteric arteries were mounted on a wire myograph, and tensions were recorded in response to cumulative phenylephrine (PE) concentrations (0.01-30μM) in the presence and absence
of BKCa channel blocker Iberiotoxin (IbTx, 100nM). In another set of experiments, tensions in response to cumulative concentration of acetylcholine (ACh) or sodium nitroprusside (SNP) were recorded. EC50s and IC50s were compared. Western immunoblotting was performed to measure expression levels of the pore forming (α) and the auxiliary (β) subunits of BKCa channels and of eNOS proteins.
Results: ET did not alter the basal tone nor the response of small and large mesenteric arteries to PE. The endothelial dependent relaxations induced by ACh, were significantly reduced in small arteries (IC50= SED; 7.52±1.44nM vs EXE; 26.7±1.23nM, P=0.00) but not in large arteries. The endothelium independent relaxations induced by SNP were also significantly reduced in both small (IC50= SED; 14.1±2.14nM vs EXE; 87.4±1.26nM, P=0.01) and in large (IC50= SED; 14.6±1.58nM vs EXE; 125.4±1.26nM, P=0.00) mesenteric arteries. IbTx did not alter the basal tone but shifted the PE-response curves to the left in the two sedentary groups namely SED(S) (P=0.01) and SED(L) (P=0.01) but not in the two exercised groups. There was no significant change in the level of protein expression of both BKCa channels' subunits and of eNOS.
Conclusion: Moderate intensity ET of ten weeks was sufficient to elicit functional adaptations which involved reduced endothelium-dependent and - independent relaxations, and reduced functional contribution of BKCa channels in opposing the
contractile responses. However, these functional adaptations were not associated with alterations in protein expression of eNOS or BKCa subunits. Taken together these results indicate an increased tendency of vasoconstriction in both small and large
mesenteric arteries after ET.
