R. Patron-Lozano2, M. I. Rodriguez-Davalos1, A. Munoz-Abraham1, J. P. Geibel1,2 1Yale University School Of Medicine,Transplantation/Surgery,New Haven, CT, USA 2Yale University School Of Medicine,Surgery,New Haven, CT, USA
Introduction: The renin-angiotensin-aldosterone system, through angiotensin II (AII), is one of the most important blood pressure regulators. The vasoconstriction caused by AII and the sodium balance effected by aldosterone have been a key target for drugs aiming to control hypertension. Angiotensin (AT) receptors have been well identified in vascular smooth muscle and renal tissue. Moreover, they have also been identified throughout the enteric epithelium, although mainly as a mitogenic agent. In the colon, the localization of functional angiotensin receptors has recently been described by our group and shows a promising potential future target for antihypertensive agents. In this study, we aimed to identify the presence of functional angiotensin receptors using intact small bowel of rats to determine if AII and AT1 receptor agents can modulate small bowel salt transport.
Materials and
Methods: We used Sprague Dawley rats (280 and 360 grams) fasted for 18 hours, in order to reduce intestinal residue. The rats were anesthetized with isoflurane and euthanized. We took 12cm of distal ileum and stripped it from its mesentery. The intestinal lumen was flushed with lactated ringer’s solution in order to remove any remaining intestinal contents. The intestinal loop was then attached to a custom perfusion chamber where it was filled with 2mL of angiotensin at a concentration of 1×10-11 M and weighed. This measurement was determined as weight at t0. The chamber was then filled with lactated ringer’s at 37C and connected to a roller pump which continuously exchanged the fluid and maintained constant temperature for 1 hour. Then, the chamber was emptied and weighed again; this measurement being t1. For control purposes, the experiment was run using the same technique but the intestinal lumen filled with 2mL of lactated ringer’s.
Results: We observed a significant decrease in weight after the administration of angiotensin at 10-11 M concentration between t0 and t1. This difference was consistent in every experiment. The mean weight difference was 93mg or 3.20% reduction in net graft weight. For the control samples, the weight remained the same at t1 or even slightly increased by almost 2% compared to the initial tissue weight.
Conclusion: We conclude that there are functional angiotensin receptors in rat small bowel that are sensitive to low dose AII(10-11M). By recording a difference in graft weight after the administration of low dose AII we proved that these receptors are not only present, but they can be stimulated provided adequate characteristics. These findings can further help us comprehend the extent of the fluid and electrolyte regulators in the body thus providing novel targets for control of hypertension and other diseases.