Effects of exercise training and hypercholesterolemia on adenosine-activation of voltage-dependent K+ channels in coronary arterioles. Journal of applied physiology (Bethesda, Md. : 1985) [J Appl Physiol] Journal article | | Title | Effects of exercise training and hypercholesterolemia on adenosine-activation of voltage-dependent K+ channels in coronary arterioles. | | Author(s) | Heaps CL, Jeffery EC, Laine GA, Price EM, Bowles DK | | Institution | Texas A&M University. | | Source | J Appl Physiol 2008 Oct 2. | | Abstract | Coronary arterioles from hypercholesterolemic swine display attenuated adenosine-mediated vasodilatation which is attributable to the elimination of voltage-dependent K(+) (Kv) channel stimulation. For the present study, we tested the hypotheses that exercise training would correct impaired adenosine-induced dilatation in coronary arterioles from hypercholesterolemic pigs through restoration of adenosine-activation of Kv channels and that vasodilatation to the receptor-independent adenylyl cyclase activator, forskolin, would also be attenuated in arterioles from hypercholesterolemic pigs. Pigs were randomly assigned to a control (NC) or high fat/high cholesterol (HC) diet for 20 weeks. Four weeks after the diet was initiated, pigs from both groups were assigned to exercise training (Ex; 5 days/week for 16 weeks) or sedentary (Sed) protocols, resulting in four groups of pigs: NC-Sed, NC-Ex, HC-Sed and HC-Ex. Arterioles (~150 microm) from both HC-Sed and HC-Ex pigs displayed impaired adenosine-mediated dilatation that was attributable to the elimination of 4-aminopyridine (4-AP; 1 mM)-sensitive Kv channel activation compared with NC counterparts. Arteriolar smooth muscle whole-cell Kv currents were significantly reduced in HC-Sed compared with NC-Sed, although HC-Ex and NC-Ex did not differ. Forskolin-mediated dilatation was attenuated by 4-AP (1 mM) and in a concentration-dependent manner by tetraethylammonium (TEA; 0.1-1 mM) in NC-Sed but not HC-Sed. Further, TEA-sensitive Kv currents were diminished in cells of HC-Sed compared with NC-Sed pigs. Quantitative RT-PCR revealed similar expression levels of Kv3.1 and 3.3 in arterioles of NC-Sed and HC-Sed swine with undetectable expression of Kv1.1, 3.2 and 3.4. Taken together, these results suggest that hypercholesterolemia-mediated attenuation of adenosine-induced vasodilatation in coronary arterioles is not corrected by exercise training and is likely attributable to an impairment in the pathway coupling adenylyl cyclase with a highly TEA-sensitive Kv channel isoform(s). Key words: electrophysiology, forskolin, coronary vasodilatation, vascular smooth muscle. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 18832757 |
|
|
| |
Advertise on this site.
| | |
|
