Pharmacological nature of nicotine-induced contraction in the rat basilar artery: involvement of arachidonic acid metabolites.
The pharmacological nature of nicotine-induced contraction in the rat basilar artery is poorly understood. The purpose of this study was to investigate the endothelium dependency and involvement of arachidonic acid metabolites in nicotine-induced contraction in the rat basilar artery. The rat basilar artery was removed from the brain and cut into a spiral preparation. Nicotine (3x10(-5) to 10(-2) M) induced the concentration-dependent contraction in the rat basilar artery, and the maximal contraction was obtained at 3x10(-3) M. The contraction induced by nicotine (3x10(-3) M) was significantly attenuated by the presence of saponin (0.05 mg/ml, 15 min). Phospholipase C (PLC) inhibitors (NCDC and U-73122), calcium-independent phospholipase A(2) (iPLA(2)) inhibitor (BEL), cyclooxygenase-2 (COX-2) inhibitors (nimesulide, L-745,337 and celecoxib), and a 5-lipoxygenase (5-LOX) inhibitor (ZM-230487) concentration-dependently attenuated the nicotine-induced contraction. A cytosolic phospholipase A(2) (cPLA(2)) inhibitor (AACOCF3), secretory phospholipase A(2) (sPLA(2)) inhibitor (indoxam), and cyclooxygenase-1 (COX-1) inhibitors (flurbiprofen and ketoprofen) did not affect the nicotine-induced contraction. From these results, it was suggested that nicotine-induced contraction in the rat basilar artery is endothelium-dependent and is due to arachidonic acid metabolites.
Ji
Xu
X
Pharmacology Division, Radioisotope Research Center, Kyoto University, Kyoto 606-8501, Japan.
Nishihashi
Tsuyoshi
T
Trandafir
Cristina C
CC
Wang
Aimin
A
Shimizu
Yoshiharu
Y
Kurahashi
Kazuyoshi
K
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism / Q000502:physiology*; D001488:Basilar Artery / Q000187:drug effects*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D016859:Lipoxygenase Inhibitors; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D064801:Phospholipase A2 Inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D012503:Saponins / Q000494:pharmacology; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D016859:Lipoxygenase Inhibitors; D018722:Nicotinic Agonists; D064801:Phospholipase A2 Inhibitors; D012503:Saponins; D016718:Arachidonic Acid; D009538:Nicotine; D010738:Type C Phospholipases