RT Journal Article
SR Electronic
T1 Effects of antihypertensive agents on intestinal contractility in the spontaneously hypertensive rat: angiotensin receptor system down regulation by losartan
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP jpet.116.237586
DO 10.1124/jpet.116.237586
A1 Glen S Patten
A1 Mahinda Y Abeywardena
YR 2016
UL http://jpet.aspetjournals.org/content/early/2016/11/30/jpet.116.237586.abstract
AB Hypertension is an inflammatory condition controlled by the renin angiotensin system and is linked to kidney disease, diabetes mellitus and recently to dysfunction of the gut. The aim of this study was to determine what effect anti-hypertensive drug treatments may have on intestinal function of the spontaneously hypertensive rat (SHR). In the first experiment SHR were treated with enalapril or hydralazine. In the second experiment SHR were treated with losartan with no-treatment as control for both experiments. All drug treatments lead to significant lowering of blood pressure after 16 weeks. At termination, intact tissue sections of ileum and colon were induced to contract ex vivo by KCl, electrical stimulation and agonists carbachol, prostaglandin E2, angiotensin I and II. There were no differences in ileal or colonic contractility due to hydralazine or enalapril compared to no-treatment SHR control. However, for the ileum, the losartan group responded significantly higher to KCl, and carbachol, while responding lower to angiotensin I and II with no difference for PGE2 compared to no-treatment SHR control. In contrast, the colon responded similarly to KCl, electrical stimulation and PGE2 but responded significantly lower to angiotensin I and II. These results demonstrate that ileum responds differently (with KCl and carbachol as agonists) to the colon after losartan treatment whilst there is a reduced contractile response in both ileum and colon following losartan treatment. Although there is little well documented major contraindication for angiotensin receptor blockers, the modulation of gut contractility by losartan may have wider implications for bowel health.