Atrophy of mesenteric sympathetic innervation may contribute to splanchnic vasodilation in rat portal hypertension

Abstract

Portal hypertension is associated with sympathetic nerve atrophy/regression in the mesenteric arterial vasculature that could contribute to the splanchnic vasodilation associated with portal hypertension.

Dysbalance in sympathetic neurotransmitter release and action in cirrhotic rats: Impact of exogenous neuropeptide Y

“…However, recent reports suggest splanchnic sympathetic atrophy in portal hypertension. In detail, marked reduction of sympathetic nerves and decreased protein expression of tyrosine-hydroxylase key enzyme for NA synthesis have been demonstrated in portal hypertensive mesenteric arteries [10][11][12]. Applying a model of repetitive electric PNS resembling sustained splanchnic vascular SNS activity, we report that cirrhotic rats display almost doubled and about 30% increased NA release caused by first and subsequent PNS, respectively.…”

“…Significant increases in PNS-induced NPY release were detected only in healthy rats, demonstrating a diminished ability of sympathetic nerves to release NPY in portal hypertensive splanchnic arteries. This could represent the functional correlate for reported downregulation and regression of sympathetic innervation in the mesenteric arterial tree in cirrhosis [10,11]. Besides local SNS downregulation, other potential mechanisms could explain NPY deficiency: unquestionably, systemic NA levels are increased in cirrhosis [3,[6][7][8][9].…”

“…Es gibt deutliche Evidenz dafür, dass bei portaler Hypertension die systemischen NA-Plasmakonzentrationen hauptsächlich von der mesenterialen NA-Produktion abhängen [5]. Aber anders als bei systemischen NAKonzentrationen sind Daten zu lokaler splanchnischer Neurotransmitter-Produktion und -Sekretion sehr spärlich vorhanden und zudem kontrovers [6][7][8][9][10][11][12].…”

“…In case of portal hypertension, systemic plasma NA levels could mainly depend on splanchnic NA production [5]. Besides systemic NA levels, data in terms of actual splanchnic synthesis/release of neurotransmitters are scarce and controversial [6][7][8][9][10][11][12]. Neuropeptide Y (NPY) is co-stored and co-released with NA from secretory vesicles of sympathetic nerve terminals, inducing potentiation of a 1 -adrenergic vasoconstriction via G-proteinassociated postsynaptic Y 1 receptors [13].…”

Pathophysiological mechanisms of portal hypertension syndrome development

“…Можливим поясненням цього може бути локальне зниження функції таких нейротропінів, як фактор росту нервів і нейротропін-3 [7,10]. До того ж підвищена експресія нейрональної NOS за участю Hsp90 у периваскулярних нейронах брижових артерій може бути додатковим чинником релаксації гладеньких м'язів судин брижі при ПГ [10,25].…”