Comparison of Neurotransmitter Release from Perivascular Nerves in C57BL/6J Mice and Wistar Rats

Abstract

It is thought that sympathetic nerve activation stimulates arterial constriction predominately through the release of three neurotransmitters: norepinephrine (NE), adenosine triphosphate (ATP) and neuropeptide Y (NPY). The aim of the current study was to examine the composition of neurotransmitter released in response to sympathetic nerve stimulation in mesenteric arteries of two commonly used wild‐type animal models. Isolated mesenteric arteries from male C57BL/6J mice and Wistar rats were mounted in a Danish Myotechnology 2‐Channel Wire Myograph System and isometric force measurements were recorded. Electrical field stimulation (EFS) was used to stimulate sympathetic perivascular nerves (PVNs) to release neurotransmitters in the presence and absence of the adrenergic receptor blocker phentolamine and/or purinergic receptor blocker NF449. Phentolamine alone blocked a significant proportion of the contractile response evoked by EFS in both mice and rats, suggesting that NE is the main sympathetic neurotransmitter in both species. Treatment with NF449 alone blocked a small proportion of the contractile response evoked by EFS in mice but did not have a significant effect in rat, suggesting that ATP may play a more important role in mice. The application of both phentolamine and NF449 nearly completely blocked the contractile response to EFS in mouse mesenteric arteries; however, in rat, a proportion of the contractile response, roughly equivalent to the response obtained in the presence of phentolamine alone, was still observed. These data suggest that the neurotransmitter composition is different between mice and rats, in particular mouse mesenteric sympathetic PVNs release NE and ATP while rat mesenteric sympathetic PVNs release NE and another non‐purinergic neurotransmitter(s).