High-fat diet alters K+-currents in porcine coronary arteries and adenosine sensitivity during metabolic inhibition.
Coronary arteries from animals on normal diets (ND) exhibit well-maintained responses to dilators under ischemic conditions. The reported altered metabolic requirements and K+-currents in blood vessels from hypercholesterolemic animals fed high-fat diets (HF) led us to hypothesize that under metabolically depressed conditions (N2/2-deoxyglucose) coronary arteries from pigs would exhibit significantly decreased responses to adenosine (ADO) as compared with pigs given ND. Diet had no major effect on responses of coronary rings to ET-1, nor on the sensitivity to ADO or 2-chloroadenosine (2-CAD) relaxation under metabolically supported conditions. During metabolic inhibition the response curves for both ADO and 2-CAD were shifted to the right (P < 0.05), with the HF group shifted about 4-fold more than ND (P < 0.05). To determine the involvement of K+-channels, ADO responses were measured in the presence of 4-aminopyridine (4-AP, 1 mM) or glybenclamide (GLYB, 10 microM). The larger shift in the HF group during metabolic inhibition was not affected by GLYB, but disappeared in the presence of 4-AP with ND now behaving similarly to HF. These results indicate that HF diet may have a 4-AP-like effect on voltage-dependent K+-channels (KV). Patch-clamp measures of whole cell K- currents showed the HF cells to have reduced 4-AP sensitive currents (P < 0.02). The 4-AP insensitive currents were similar in both groups. Thus, reduced KV channel activity may play a role in the depressed ADO relaxation associated with metabolic inhibition of HF coronary arteries. These factors may place the coronary circulation of HF at increased risk during an ischemic episode.
Franke
R
R
Department of Medical Pharmacology and Physiology, School of Medicine, University of Missouri, Columbia, Missouri 65212, USA.
Yang
Y
Y
Rubin
L J
LJ
Magliola
L
L
Jones
A W
AW
D000241:Adenosine / Q000494:pharmacology*; D000818:Animals; D003331:Coronary Vessels / Q000187:drug effects* / Q000378:metabolism; D004041:Dietary Fats / Q000378:metabolism / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004734:Energy Metabolism / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000378:metabolism*; D013556:Swine, Miniature; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
D004041:Dietary Fats; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D000241:Adenosine