Angiotensin-II and the oesophagus

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The effects of angiotensin II receptor antagonists, like losartan, on the esophagus are not well understood, with some studies indicating they may relax smooth muscles, potentially increasing gastro-oesophageal reflux and heartburn symptoms. However, other research has failed to establish this connection, showing that calcium channel antagonists can have this effect while beta-blockers do the opposite. There is a lack of studies examining the impact of ACE inhibitors, such as perindopril, on esophageal function, despite their similar mechanism of reducing AT1 receptor stimulation. The differences in how angiotensin II receptor antagonists and ACE inhibitors operate suggest potential variances in their effects on the esophagus. Further information on ACE inhibitors' influence on esophageal function and comparisons with angiotensin II receptor antagonists is sought.
DrGreg
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According to what I've been able to find in published papers, the effects of angiotensin II receptor antagonists[/color] (such as losartan) on the oesophagus seem to be poorly understood. Some studies[1][2] suggest that as well as the desirable effect of relaxing the smooth muscles of blood vessels to reduce blood pressure, they may have the undesirable effect of relaxing the smooth muscles of the oesophagus and the lower oesophageal sphincter, increasing the chance of gastro-oesophageal reflux and heartburn symptoms. Another study[3] failed to show such a connection, while demonstrating that a calcium channel antagonist does have this effect but a beta-blocker has the opposite effect.

I have failed to find any studies into similar effects of ACE inhibitors[/color] (such as perindopril). Both types of drug are similar in that they reduce stimulation of AT1 receptors, but do so by different mechanisms. Ang-II receptor antagonists work by directly blocking the AT1 receptors (to which the body responds by increasing Ang-II production) whereas ACE inhibitors work by decreasing the production of Ang-II. So you might expect some similarities between the effects of the two drug types but also some differences.

So my question is, does anyone have any information on the effect of ACE inhibitors on oesophageal function, and any comparison with the effects of angiotensin II receptor antagonists?



References

[1] Casselbrant et al, "Actions by angiotensin II on esophageal contractility in humans"[/color], Gastroenterology. 2007 Jan; 132 (1):249-60. Epub 2006 Nov 10.

[2] Casselbrant et al, "Angiotensin II receptors are expressed and functional in human esophageal mucosa"[/color], AJP - GI November 1, 2009 vol. 297 no. 5 G1019-G1027

[3] Yoshida et al, "Effects of anti-hypertensive drugs on esophageal body contraction"[/color], World J Gastroenterol. 2010 February 28; 16(8): 987–991.

[4] Rattan et al, "Comparison of angiotensin II (Ang II) effects in the internal anal sphincter (IAS) and lower esophageal sphincter smooth muscles"[/color], Life Sciences Volume 70, Issue 18, 22 March 2002, Pages 2147–2164

[5] Spak et al, "Angiotensin II-induced contractions in human jejunal wall musculature in vitro"[/color], Acta Physiol (Oxf). 2008 Jun; 193(2):181-90. Epub 2007 Dec 10.
 
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