Nicotine exposure, mimicked smoking, directly and indirectly enhanced protein kinase C activity in isolated canine basilar artery, resulting in enhancement of arterial contraction.
Cigarette smoking is a significant risk factor in the incidence of cerebrovascular disorders. Among the many compounds in cigarette smoke, nicotine is considered to most significantly affect cerebral arterial tone. The purpose of this study is to investigate precise pharmacological effects of nicotine on the regulation of cerebral arterial tone. To mimic smoking, a low concentration of nicotine (10(-6) mol/L), which is equivalent to the serum level of habitual smokers, was treated for 1 hour in an isometric tension study and for 24 hours in a study using cultured vascular endothelial cells (VECs). Using the canine basilar artery, the effect of nicotine on uridine 5'-triphosphate (UTP)-induced vasoconstriction was examined in the isometric tension study. Protein kinase C (PKC) activity in the canine basilar artery was measured by enzyme immunoassay. Endothelial function was assessed by endothelium-dependent vasodilatation and endogenous nitric oxide (NO) synthesis in VECs using a fluorescent indicator, diaminofluorescein-FM diacetate (DAF-FM/DA). Nicotine significantly enhanced UTP-induced contraction and PKC activity in the artery, and attenuated endothelium-dependent vasodilatation and NO synthesis in VECs. Because PKC activity was increased by de-endothelialization itself, endothelial dysfunction by nicotine enhances PKC activity. Because PKC was further activated by nicotine even in the de-endothelialized artery, nicotine directly affects PKC activities in smooth muscle. These results indicate that nicotine potentiates contractile response through direct and indirect PKC activation in the canine basilar artery.
Koide
Masayo
M
Department of Neurosurgery, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan.
Nishizawa
Shigeru
S
Yamamoto
Seiji
S
Yamaguchi
Mitsuo
M
Namba
Hiroki
H
Terakawa
Susumu
S
D000818:Animals; D001488:Basilar Artery / Q000187:drug effects* / Q000502:physiology*; D004285:Dogs; D004730:Endothelium, Vascular / Q000187:drug effects; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D009538:Nicotine / Q000494:pharmacology*; D009569:Nitric Oxide / Q000096:biosynthesis / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism* / Q000502:physiology; D012680:Sensitivity and Specificity; D012907:Smoking; D014544:Uridine Triphosphate / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology
D009569:Nitric Oxide; D009538:Nicotine; D011493:Protein Kinase C; D014544:Uridine Triphosphate