Morphological studies demonstrate the presence of close apposition between sympathetic and parasympathetic nerve terminals in cerebral arteries in several species, suggesting an interaction between nerve terminals in regulating cerebral circulation. In vitro studies using isolated cerebral arteries have shown that norepinephrine (NE), released from cerebral perivascular sympathetic nerve terminals upon application of nicotine, diffuses to act on b2-adrenoceptors located on neighboring nitrergic nerves to release nitric oxide (NO) leading to vasodilation. This axo-axonal interaction hypothesis is supported by results of present in vivo studies in anesthetized rats. Electrical stimulation of superior cervical ganglion (SCG) and topical application of nicotine (10–30 mM) on basilar arteries caused dilation with increased blood flow (BF) in basilar arteries in normotensive Wistar-Kyoto rats (WKY) of different ages. The increased BF was blocked by 7-nitroindazole (a NO synthesis inhibitor) and ICI 118,551 (a b2-adrenoceptor antagonist) but was not affected by atenolol (a b1-adrenoceptor antagonist). These inhibitors did not affect vasodilation or increased BF induced by acetylcholine (1 mM, topical application). In 6-week-old spontaneously hypertensive rats (SHRs), electrical stimulation of SCG and topical applications of nicotine induced similar nitrergic dilation and increased BF of basilar arteries as found in WKY. These increases in both dilation and BF, however, were significantly diminished in 12-week and 24-week old SHRs. In summary, activation of cerebral perivascular sympathetic neurons in vivo causes predominantly NO-mediated vasodilation with increased BF via axo-axonal interaction mechanism. This unique mechanism is altered in established hypertension (supported by Taiwan NSC, Tzu Chi University & Tzu Chi Foundation).