Actions by Angiotensin II on Esophageal Contractility in Humans Anna Casselbrant, Anders Edebo, Johanna Wennerblom, Hans Lönroth, Herbert F. Helander, Michael Vieth, Lars Lundell, Lars Fändriks  Gastroenterology  Volume 132, Issue 1, Pages 249-260 (January 2007) DOI: 10.1053/j.gastro.2006.11.010 Copyright © 2007 AGA Institute Terms and Conditions

Figure 1 (Left panel) Illustration of the high resolution manometry and potential difference (PD) catheter. Hydrostatic pressure and PD were recorded at 15 sideholes (interval: 1 cm) straddling the esophagogastric junction. (Right panel) The PD recordings were displayed as a function of distance from nostril. A step-up of PD values indicates the transition from esophageal squamous to gastric columnar mucosa (corresponding to the endoscopic Z-line). Because the nasogastric catheter is fixed at one nostril, movements of the PD step-up along the x-axis indicate axial movements of the esophagus. (The simultaneous esophageal manometric recordings are not shown.) Gastroenterology 2007 132, 249-260DOI: (10.1053/j.gastro.2006.11.010) Copyright © 2007 AGA Institute Terms and Conditions

Figure 2 Immunostaining of musculature from human esophageal body (EB) and the lower esophageal sphincter (LES). (A, B) Staining for Angiotensin II type 1 (AT1) receptors in the muscular bundles (A) and in the wall of small blood vessels close to the muscle cells (B). (C) Negative control for AT1 receptors. (D, E, G, H) Immunostaining to Angiotensin II type 2 (AT2) receptors and angiotensin-converting enzyme appeared to be localized in the blood vessel walls (E, H) but was weak or absent in the muscle cells (D, G). (F, I) Negative controls for AT2 receptors (F), and for ACE (I). (J, left) a typical Western blot for AT1 with a band at 41 kDa in the positive control cell lysate PC12 and in human distal esophageal body and LES muscular specimens. (J, right) AT2 receptor analysis with a band at 44 kDa in the positive control cell lysate KNRK and with faint staining in muscular specimens from esophageal body and LES. Magnification, ×40, with brown indicating positive staining. Gastroenterology 2007 132, 249-260DOI: (10.1053/j.gastro.2006.11.010) Copyright © 2007 AGA Institute Terms and Conditions

Figure 3 Concentration–response curves showing the contractile effect of Angiotensin II (Ang II) in circular smooth muscle of the distal part of human esophageal body (A–C) and the lower esophageal sphincter (D–F). Treatment with the Angiotensin II (Ang II) type 1–receptor antagonist losartan (10−7 M and 10−5 M; A, D), with Ang II type 2 receptor antagonist PD123319 10−7 M (B, E), and with tetrodotoxin (TTX) 10−6 M (C, F). Effects of Ang II are expressed as a percentage of the contraction induced by 10−4 M bethanechol. Data are plotted as means ± SEM. Gastroenterology 2007 132, 249-260DOI: (10.1053/j.gastro.2006.11.010) Copyright © 2007 AGA Institute Terms and Conditions

Figure 4 From the on-line display of high-resolution manometry and potential difference (PD) at the esophagogastric junction of a healthy volunteer (female, age 30 years). The panels represent intraluminal pressure and PD along the distal esophagus and the esophagogastric junction at consecutive time points after a swallow. Distance (cm) from nostril is indicated on the x-axis. (A) Baseline conditions: a high-pressure zone can be identified between a distance of 47 to 51 cm from the nostril, and a sharp step-up in PD values is located at 48–51 cm. (B) Eleven to 12 seconds after a voluntary swallow, the high-pressure zone has disappeared, and the PD step-up has moved to 45 cm from the nostril, indicating an esophageal shortening. (C) Sixteen seconds after swallowing, a peristaltic contraction appears, and the PD step-up is returning from its retracted position. (D) Twenty-five seconds after swallowing; the peristaltic contraction establishes a new high-pressure zone at 48–51 cm, and the PD step-up has returned to its original position, starting 48 cm from the nostril. Gastroenterology 2007 132, 249-260DOI: (10.1053/j.gastro.2006.11.010) Copyright © 2007 AGA Institute Terms and Conditions

Figure 5 Data from high-resolution manometry and PD recordings of the esophageal body during control and after candesartan intake in healthy volunteers (n = 13) on 2 separate study days. (A) Amplitudes of the primary peristaltic pressure wave were significantly lower after intake of candesartan. (B, C) The propulsion velocity of the pressure wave and the oral retraction of the PD step-up were similar and independent of treatment with candesartan. The median value in each group is indicated. *Significant difference, P < .05. Gastroenterology 2007 132, 249-260DOI: (10.1053/j.gastro.2006.11.010) Copyright © 2007 AGA Institute Terms and Conditions

Figure 6 (A–C) Data from high-resolution manometry and potential difference (PD) recordings of the lower esophageal sphincter (LES) during control and after candesartan intake in healthy volunteers (n = 13) on 2 separate study days. (A) The length of the high-pressure zone (HPZ) was significantly shorter in presence of candesartan. (B) The basal pressure of the HPZ was significantly lower after candesartan. (C) The postbelch contraction of the LES was similar, independent of treatment with candesartan. The median value in each group is indicated (*significant difference, P < .05). Gastroenterology 2007 132, 249-260DOI: (10.1053/j.gastro.2006.11.010) Copyright © 2007 AGA Institute Terms and Conditions

Figure 7 From the on-line display of high-resolution manometry and potential difference (PD) at the esophagogastric junction of a healthy volunteer (male, age 30 years). The panels represent intraluminal pressure and PD along the distal esophagus and the esophagogastric junction at consecutive time points during belching after gastric distension with 500 mL of air. Distance (cm) from nostril is indicated on the x-axis. (A) Baseline conditions: a high-pressure zone can be identified between 46 to 52 cm from the nostril and a sharp step-up in PD values is located at 48 to 50 cm. (B) Two minutes after insufflation of 500 mL of air into the stomach, the high-pressure zone has vanished and the subject experiences gas evacuation. The high-pressure zone has disappeared simultaneously with occurrence of a marked retraction of the PD step-up (now starting at 40 cm from nostril). (C) A peristaltic contraction moving aborally; the retracted PD step-up begins to return to its original position. (D) 15 to 30 seconds after gas evacuation, a new sustained high-pressure zone is established at 45 to 50 cm, and the PD step-up has returned to its original position, starting 48 cm from the nostril. Gastroenterology 2007 132, 249-260DOI: (10.1053/j.gastro.2006.11.010) Copyright © 2007 AGA Institute Terms and Conditions