Vascular relaxation stimulated with acetylcholine involves inducible and constitutive NO‐synthases and cyclooxygenase activation six hours after cecal ligation and perforation (CLP).

Abstract

Several studies have demonstrated a systemic hypotension in septic shock induced by CLP that is mainly attributed to nitric oxide (NO). The present work aimed to study the endothelium‐dependent vascular relaxation induced by acetylcholine (ACh) in CLP and sham‐operated (SO) rat aortic rings and to identify the NO‐synthase (NOS) isoform involved in this response by the selective inhibitors (eNOS, L‐NNA 100 μM), (nNOS, 7‐NI 100 μM) and inducible iNOS (1400W 10 μM), and the non‐selective L‐NAME 100 μM and the role of cyclooxygenase (COX). Mean arterial pressure was progressively reduced 6h after CLP. Rats were killed 6h after CLP and concentration‐effect curves for ACh were constructed in aortic rings in the absence or after incubation for 30 min with the given inhibitor. Both maximum relaxation (ME) and potency (pD2) induced by ACh were similar in CLP (99.4±1.3%; pD2 7.20±0.15, n=7) and in SO (95.9±3.0%, pD2 7.36±0.15, n=4). The relaxation was more inhibited in SO (L‐NAME 3.2±6.8%; L‐NNA 4.5±5.2%; 7‐NI 61.3±3.9%) than in CLP (L‐NAME 13.9±7.5%; L‐NNA 12.0±2.4%; 7‐NI 95.4±1.5%). However, these responses were similar after the combination of the COX and NOS inhibitors. In the presence of 1400W, the potency but not the ME of ACh was reduced in CLP. In conclusion, ACh induces aorta relaxation via iNOS and constitutive NOS and product(s) of COX 6h after CLP. Supported by CAPES, CNPq and FAPESP.