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 (3 × 10 − 5 to 10 − 2 M) induced the concentration-dependent contraction in the rat basilar artery, and the maximal contraction was obtained at 3 × 10 − 3 M. The contraction induced by nicotine (3 × 10 − 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.