Exercise training activates large-conductance calcium-activated K(+) channels and enhances nitric oxide production in rat mesenteric artery and thoracic aorta.
Exercise training has reversible beneficial effects on cardiovascular diseases, e.g. hypertension, which may result from a decrease in systemic vascular resistance. The purpose of this study was to investigate possible mechanisms associated with the changes in vascular reactivity in large and small arteries with vasoconstrictors and vasodilators in rats after exercise. Wistar-Kyoto rats were trained for 8 weeks (Ex group) on a treadmill and compared with sedentary counterparts (Sed group). After the measurement of blood pressure and heart rate at 8 weeks, rat mesenteric arteries and thoracic aortas were excised and prepared as rings for this study. In addition, special care was taken not to damage the endothelium of the preparations. Our results showed that exercise training for 8 weeks (1) not only prevented an increase in blood pressure but also caused a fall in heart rate, (2) attenuated the contractions induced by both prostaglandin F(2alpha) (PGF(2alpha)) and high K(+) in the mesenteric artery, but reduced the PGF(2alpha)-induced contraction in the aorta only, (3) enhanced the relaxation elicited by acetylcholine (ACh) in both mesenteric arteries and aortas, and (4) increased nitrate [an indicator of nitric oxide (NO) formation] in plasma. The enhancement of ACh-induced relaxation in the mesenteric arteries in the Ex group was suppressed by pretreatment with N(omega) -nitro-L-arginine methyl ester (L-NAME), tetraethylammonium (TEA; a nonselective inhibitor of K(+) channels) or charybdotoxin [CTX; a selective inhibitor of large-conductance calcium-activated K(+) (BK(Ca)) channels], whereas in the aorta that response was attenuated by TEA or CTX and almost completely abolished by L-NAME. However, with a combination of L-NAME plus CTX in the mesenteric artery, ACh-induced relaxation was completely abolished in the Sed group, but not in the Ex group. These results suggest that in addition to NO, activation of BK(Ca) channels in the vascular beds, at least in part, also contributes to vasodilatation in animals with exercise training.
Chen
S J
SJ
Department of Pharmacology, National Defense Medical Center, Taipei, Taiwan, ROC.
Wu
C C
CC
Yen
M H
MH
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism*; D001794:Blood Pressure; D002318:Cardiovascular Diseases / Q000378:metabolism / Q000517:prevention & control / Q000628:therapy; D018999:Charybdotoxin / Q000494:pharmacology; D015237:Dinoprost / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D006339:Heart Rate; D051036:Large-Conductance Calcium-Activated Potassium Channels; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000378:metabolism*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D010805:Physical Conditioning, Animal / Q000502:physiology*; D015221:Potassium Channels / Q000378:metabolism*; D024681:Potassium Channels, Calcium-Activated; D051381:Rats; D011921:Rats, Inbred WKY; D019789:Tetraethylammonium / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
D051036:Large-Conductance Calcium-Activated Potassium Channels; D015221:Potassium Channels; D024681:Potassium Channels, Calcium-Activated; D014665:Vasodilator Agents; D018999:Charybdotoxin; D009569:Nitric Oxide; D019789:Tetraethylammonium; D015237:Dinoprost; D019001:Nitric Oxide Synthase; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester