Role of Phenylethanolamine‐N‐methyltransferase on Nicotine‐Induced Vasodilation in Rat Cerebral Arteries

Objective The sympathetic–parasympathetic (or axo–axonal) interaction mechanism mediated that neurogenic relaxation, which was dependent on norepinephrine (NE) releases from sympathetic nerve terminal and acts on β 2 ‐adrenoceptor of parasympathetic nerve terminal, has been reported. As NE is a weak β 2 ‐adrenoceptor agonist, there is a possibility that synaptic NE is converted to epinephrine by phenylethanolamine‐ N ‐methyltransferase (PNMT) and then acts on the β 2 ‐adrenoceptors to induce neurogenic vasodilation. Methods Blood vessel myography technique was used to measure relaxation and contraction responses of isolated basilar arterial rings of rats. Results Nicotine‐induced relaxation was sensitive to propranolol, guanethidine (an adrenergic neuronal blocker), and N ω ‐nitro‐ l ‐arginine. Nicotine‐ and exogenous NE‐induced vasorelaxation was partially inhibited by LY‐78335 (a PNMT inhibitor), and transmural nerve stimulation depolarized the nitrergic nerve terminal directly and was not inhibited by LY‐78335; it then induced the release of nitric oxide (NO). Epinephrine‐induced vasorelaxation was not affected by LY‐78335. However, these vasorelaxations were completely inhibited by atenolol (a β 1 ‐adrenoceptor antagonist) combined with ICI‐118,551 (a β 2 ‐adrenoceptor antagonist). Conclusions These results suggest that NE may be methylated by PNMT to form epinephrine and cause the release of NO and vasodilation. These results provide further evidence supporting the physiological significance of the axo–axonal interaction mechanism in regulating brainstem vascular tone.