Nicotine Exposure, Mimicked Smoking, Directly and Indirectly Enhanced Protein Kinase C Activity in Isolated Canine Basilar Artery, Resulting in Enhancement of Arterial Contraction

Abstract

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 À6 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 0 -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 endotheliumdependent vasodilatation and NO synthesis in VECs. Because PKC activity was increased by deendothelialization 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.

Structural and Functional Alteration of Blood Vessels Caused by Cigarette Smoking: An Overview of Molecular Mechanisms

“…Nicotine exposure potentiates norepinephrine-induced vasoconstriction in hamster cheek pouch arterioles [46], while the contractility of canine cerebral arteries is increased by nicotine through impairment of endothelial function and activation of PKC activity [47]. Chronic nicotine exposure blunts NO-induced vasodilation [40], suggesting vascular smooth muscle dysfunction as an additional component.…”

“…Cigarette smoking causes an upregulation of voltage-gated Ca 2+ channels and a downregulation of Ca 2+ -activated K + (BK) channels in rat cerebral arteries, effects that will attenuate NO-mediated dilation [40]. In canine basilar arteries nicotine potentiates contractile response through PKC activation [47].…”

Nicotine Replacement Therapy After Subarachnoid Hemorrhage Is Not Associated With Increased Vasospasm

“…11 Koide and colleagues studied canine basilar arterial rings that were exposed to nicotine for 1 hour with endotheliumintact and de-endothelialized samples and no contractile responses were seen on isometric tension studies using uridine triphosphate in either group. 12 They also measured protein kinase C activity, measured substance P-induced vasodilation and NO synthesis, and concluded that nicotine attenuated endothelium-dependent vasodilation by substance P, decreased NO synthesis, and increased protein kinase C activity but that ultimately nicotine does not cause vasoconstriction in canine basilar arteries; however, it may impair endothelial function and enhance protein kinase C activity resulting in an artery prone to vasoconstriction.…”

The clinical significance and reliability of self-reported smoking status in patients with intracranial aneurysms: A review

“…Tobacco smoke has been found to increase both blood viscosity and blood volume [23][24][25]. Tobacco smoke also causes vasoconstriction via the inhibition of eNOS and impaired nitric oxide signaling [26][27][28][29]. Therefore, as the viscosity, volume (and flow) increase and as the diameter of the vessel decreases, wall shear stress increases.…”