Comparison of the effects of neuropeptide Y and noradrenaline on rat gastric mucosal blood flow and integrity

Abstract

The effects of neuropeptide Y (NPY) and noradrenaline on rat gastric mucosal blood flow, as estimated by laser Doppler flowmetry (LDF), have been examined. In addition, the ability of NPY and noradrenaline to induce acute mucosal haemorrhagic damage has also been assessed. Close‐arterial infusion of NPY (0.05–0.2 nmol kg−1 min−1) for 10 min in the anaesthetized rat induced a dose‐dependent fall in LDF, but had minimal effects on systemic arterial blood pressure. Higher doses of NPY did not produce any further reduction in LDF. Close‐arterial infusion (0.1–0.4 nmol kg−1 min−1) of the structurally related peptide YY (PYY) or pancreatic polypeptide (PP), had inconsistent actions in decreasing LDF. Close‐arterial infusion of noradrenaline (30–90 nmol kg−1 min−1) dose‐dependently reduced gastric LDF. Local infusion of NPY (0.1 and 0.2 nmol kg−1 min−1) or noradrenaline (45 and 60 nmol kg−1 min−1) resulted in dose‐related increases in the area of mucosal hemorrhagic damage. Pretreatment with the α1‐adrenoceptor antagonist, prazosin (0.1 mg kg−1, i.v.) significantly reduced the effect of noradrenaline, but not NPY, on both LDF and mucosal damage. These findings indicate that NPY and noradrenaline act directly on the gastric microvasculature to induce vasoconstriction and both can induce acute mucosal damage. Therefore endogenous NPY, like noradrenaline could play a modulatory role in regulating vascular tone and may influence mucosal integrity.

Different subpopulations of cholinergic and nitrergic myenteric neurones project to mucosa and circular muscle of the guinea-pig gastric fundus

“…It is likely that such functional differentiation is also present in the gastric myenteric plexus, because studies on the innervation pattern of the musculature and the mucosa of the guinea-pig stomach have revealed differences in the distribution and density of ChAT-, NPY-, SP-and NOS-positive nerve fibres (Schultzberg et al 1980;Furness et al 1983Furness et al , 1994Keast et al 1985;Mawe et al 1989). In addition, transmitters used by the ENS, such as acetylcholine, NO, SP or NPY, modulate gastric motility (Milenov and Golenhofen 1983;Jin et al 1993;Meulemans et al 1993;, mucosal blood flow (Saperas et al 1995;Chen et al 1993;Holzer 1995;Tepperman and Whittle 1991), acid secretion (Hersey and Sachs 1995;Tsai and Cheng 1990;Zanelli et al 1992;Penner et al 1993), pepsinogen secretion (Hirschowitz and Sachs 1969;Vigna et al 1989;Kitsukawa et al 1996;Raufman and Singh 1991), bicarbonate secretion (Fändriks 1986;Bilski and Konturek 1994;Takeuchi et al 1993) and mucus secretion (Brown et al 1992;Price et al 1994).…”

A study of the antiulcer mechanisms of propanolol in rats

“…Propranolol has also been reported to reduce stress-induced elevations of circulatory noradrenaline and gastrin levels [35]. As hypnotic drug like phenobarbitone produces antiulcer action [36] and adrenergic agents adversely affect gastric mucosa [3,37], the modifications of the central nervous system and the adrenergic pathway could also explain the protective action of propranolol on stress-induced gastric mucosal damage in rats.…”

“…Available evidence indicates that c~-adrenoceptor agonists produce an adverse effect on the gastric mucosa [3]. In contrast, propranolol, a non-selective r antagonist and some other/3-adrenoceptor antagonists are effective Correspondence to: C. H. Cho in reducing portal vein pressure and incidence of upper gastrointestinal haemorrhage in portal hypertensive patients [4][5][6][7].…”

Effects of noradrenaline and neuropeptide Y on rat mesenteric microvessel contraction

“…These data are in good agreement with previous studies on many isolated large blood vessels and with mean arterial pressure data obtained following systemic NPY administration (Wahlestedt and Reis 1993;Michel and Rascher 1995). Thus, NPYinduced vasoconstriction appears to occur via a YI subtype in most vascular beds including the mesenteric resistance vasculature, but examples of Y2 (Michel et al 1990;Modin et al 1991;Tessel et al 1993) and Y3 NPY receptormediated vasoconstriction (Tepperman and Whittle 1991) have also been presented.…”