Angiotensin II receptor blockade - Importance for intestinal smooth muscle tone

Abstract

The significance of AT(1) and AT(2) receptor subtypes for the development of Angiotensin II (Ang II)-induced contractions of different intestinal segments was investigated. Longitudinal strips from rat jejunum, ileum, colon and rectum were prepared and treated by Ang II in a dose of 1 mu M. The specific effects on Ang II receptors were studied by pretreatment with the selective AT(1) antagonist Losartan (100 nM) or AT(2) receptor blocker PD 123319 (100 nM). The recorded force vs. time curves of smooth muscle contractions were explored by calculation of amplitudes, integral force, the power of the contraction, as well as time parameter analysis. The application of Losartan caused significant reduction of the amplitude of smooth muscle contraction of preparations from colon and rectum (2.53 +/- 0.12 g and 2.79 +/- 0.25 g, respectively) in comparison to those provoked with Ang II alone (3.43 +/- 0.38 g and 4.74 +/- 0.44 g). The blockade of AT(1) receptors completely neutralized Ang II-provoked jejunal activity. Pretreatment with PD 1233319 caused significant reduction of the amplitude of jejunal and rectal contractions (0.47 +/- 0.08 g and 2.86 +/- 0.33 g, respectively) and led to significantly higher amplitude of the ileal smooth muscle response (2.11 +/- 0.16 g). The results indicate the predominant role of AT(1) receptors for the induction of smooth muscle contraction. The blockade of AT(2) receptors affects both phases of the smooth muscle contraction - AT(2) receptors are of importance for the development of the intestinal response to Ang II, especially for the initiation and maintenance of the rectal muscle contraction.