title: Effects of Antihypertensive Agents on Intestinal Contractility in the Spontaneously Hypertensive Rat: Angiotensin Receptor System Downregulation by Losartan.
abstract: 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 antihypertensive drug treatments may have on intestinal function of the spontaneously hypertensive rat (SHR). In the first experiment, SHRs were treated with enalapril, hydralazine, or with no treatment as a control. In the second experiment, SHRs were treated with losartan or with no treatment as a control. All drug treatments led to significant lowering of blood pressure after 16 weeks. At termination, intact tissue sections of the ileum and colon were induced to contract ex vivo by KCl; electrical stimulation; and agonists carbachol, angiotensin II, and prostaglandin E2(PGE2). There were no differences in ileal or colonic contractility due to hydralazine or enalapril compared with no-treatment SHR control. However, for the ileum, the losartan group responded significantly more to KCl and carbachol while responding less to angiotensin II, with no difference for PGE2compared with the no-treatment SHR control. In contrast, the colon responded similarly to KCl, electrical stimulation, and PGE2but responded significantly less to angiotensin II. These results demonstrate that the ileum responds differently (with KCl and carbachol as agonists) to the colon after losartan treatment, whereas there is a reduced contractile response in both the ileum and colon following losartan treatment. Although there are few well documented major contraindications for angiotensin receptor blockers, the modulation of gut contractility by losartan may have wider implications for bowel health.
authors.affiliation: CSIRO Health and Biosecurity, Adelaide BC, South Australia, Australia glen.patten@csiro.au.
authors.forename: Glen Stephen
authors.initials: GS
authors.lastname: Patten
authors.affiliation: CSIRO Health and Biosecurity, Adelaide BC, South Australia, Australia.
authors.forename: Mahinda Yapa
authors.initials: MY
authors.lastname: Abeywardena
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D003106:Colon / Q000187:drug effects / Q000503:physiopathology; D015536:Down-Regulation / Q000187:drug effects*; D007082:Ileum / Q000187:drug effects / Q000503:physiopathology; D007422:Intestines / Q000187:drug effects* / Q000503:physiopathology*; D019808:Losartan / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects*; D051381:Rats; D011918:Rats, Inbred SHR; D011945:Receptors, Angiotensin / Q000378:metabolism*
chemical_list: D000959:Antihypertensive Agents; D011945:Receptors, Angiotensin; D019808:Losartan