Angiotensin II receptors are expressed and functional in human esophageal mucosa

Abstract

Only few studies have been devoted to the actions of the renin-angiotensin system (RAS) in the human gastrointestinal tract. The present study was undertaken to elucidate the expression and action of RAS in the human esophageal mucosa. Mucosal specimens with normal histological appearance were obtained from healthy subjects undergoing endoscopy and from patients undergoing esophagectomy due to neoplasm. Gene and protein expressions of angiotensin II (Ang II) receptor type 1 (AT(1)) and type 2 (AT(2)) and angiotensin-converting enzyme (ACE) were analyzed. In vivo functionality in healthy volunteers was reflected by assessing transmucosal potential difference (PD). Ussing chamber technique was used to analyze the different effects of Ang II on its AT(1) and AT(2) receptors. Immunoreactivity to AT(1) and AT(2) was localized to stratum superficiale and spinosum in the epithelium. ACE, AT(1), and AT(2) were found in blood vessel walls. Transmucosal PD in vivo increased following administration of the AT(1) receptor antagonist candesartan. In Ussing preparations mean basal transmural PD was -6.4 mV, epithelial current (I(ep)) 34 muA/cm(2), and epithelial resistance (R(ep)) 321 Omega.cm(2). Serosal exposure to Ang II increased PD as a result of increased I(ep), whereas R(ep) was constant. Ang II given together with the selective AT(1)-receptor antagonist losartan, or AT(2) agonist C21 given alone, resulted in a similar effect. Ang II given in presence of the AT(2)-receptor antagonist PD123319 did not influence PD, but I(ep) decreased and R(ep) increased. In conclusion, Ang II receptors and ACE are expressed in the human esophageal epithelium. The results suggest that AT(2)-receptor stimulation increases epithelial ion transport, whereas the AT(1) receptor inhibits ion transport and increases R(ep).

In vitroassessment of epithelial electrical resistance in human esophageal and jejunal mucosae and in Caco-2 cell layers

“…For example, epithelial resistance has been shown to be more sensitive than transmural resistance for indicating presence of colonic mucosal inflammation [7]. In the literature, there are so far very few studies on human small intestinal and esophageal epithelial resistance [8,[33][34][35]. The R ep of adult human jejunum in the present study was lower than reported previously in children when using impedance spectroscopy (»20 W*cm 2 ) [34].…”

RETRACTION: Role of Angiotensin-(1–7) in Gastroprotection against Stress-Induced Ulcerogenesis. The Involvement of Mas Receptor, Nitric Oxide, Prostaglandins, and Sensory Neuropeptides

“…Reaction to stress is mediated via two distinct but unrelated systems: the hypothalamic-pituitary-adrenocortical (HPA) system and the sympathoadrenal system (Goldstein and McEwen, 2002;Saavedra et al, 2006). Ang II receptor subtypes AT 1 and AT 2 were detected in the human esophageal, gastric, small intestinal, and colonic mucosa (Hirasawa et al, 2002;Casselbrant et al, 2009;Hallersund et al, 2011). The antagonists of Ang II AT 1 receptors attenuated gastric injury induced by ischemia-reperfusion, cold stress, and indomethacininduced damage in rodents due to an inhibition of sympathoadrenal axis and the attenuation of vasoconstrictor and proinflammatory activity of Ang II (Pavel et al, 2008;Morsy et al, 2009;Gemici et al, 2010;Saavedra et al, 2011;Shiotani et al, 2011).…”

The angiotensin II type 2 receptor and the gastrointestinal tract

“…7,37 Furthermore, in the healthy oesophageal mucosa, both AT 1 and AT 2 receptors are present on the surface squamous epithelium as well as, not that surprisingly, in close relation to blood vessels in deeper parts. 42 The epithelial location of Ang II receptors is intriguing. Preliminary results from experiments using human oesophageal mucosae mounted in Ussing-chambers suggest Ang II-mediated regulation of ion transport as well as paracellular permeability utilising both the receptor subtypes.…”