Effects of phorbol ester on vasodilation induced by endothelium-dependent or endothelium-independent vasodilators in the mesenteric arterial bed.
The effects of phorbol ester, phorbol 12-myristate 13-acetate (PMA), on vasodilation induced by endothelium-dependent or independent vasodilators in the mesenteric arterial bed were examined. In mesentery precontracted with methoxamine, acetylcholine (ACh) produced a concentration-dependent vasodilation, but ACh-induced vasodilation was significantly reduced when the tonus of the mesentery was raised by an equieffective concentration of PMA. Sodium nitroprusside (SNP) and forskolin also caused a concentration-dependent relaxation in the mesenteric arterial bed pre-contracted with methoxamine, but could not induce relaxation in mesentery precontracted with PMA. In mesentery precontracted with PMA or methoxamine, ACh-induced vasodilation was significantly inhibited by tetraethylammonium (TEA), but not by ouabain, glibenclamide, or apamin. ACh-induced vasodilation was significantly inhibited by NG-nitro-L-arginine (L-NNA), whereas L-NNA was not capable of effectively inhibiting the ACh-induced vasodilation of the mesentery precontracted with PMA. These results suggest that stimulation of protein kinase C (PKC) by phorbol ester (PMA) in the mesenteric arterial bed inhibits the relaxation of vascular smooth muscle (VSM) in response to cyclic nucleotides. Furthermore, the endothelium of the mesenteric arterial bed may release endothelium-derived hyperpolarizing factor (EDHF), in addition to nitric oxide (NO), into the mesentery.
Kamata
K
K
Department of Physiology and Morphology, Hoshi University, Tokyo, Japan.
Chikada
S
S
Umeda
F
F
Kasuya
Y
Y
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D001685:Biological Factors / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects*; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D051381:Rats; D017208:Rats, Wistar; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects*
D000889:Anti-Arrhythmia Agents; D001685:Biological Factors; D014662:Vasoconstrictor Agents; C067410:endothelium-dependent hyperpolarization factor; D019001:Nitric Oxide Synthase; D000109:Acetylcholine; D013755:Tetradecanoylphorbol Acetate