CALCIUM-ACTIVATED POTASSIUM CHANNEL-MEDIATED ARTERIOLAR RELAXATION DURING ENDOTOXIC SHOCK

Abstract

ABSTRACT

The role of calcium-activated potassium (KCa) channels in the in vivo relaxation of arterioles was investigated before endotoxin shock (Pre-ENDT) and during endotoxin shock at 180 min (Post-ENDT). Diameters of 2nd and 3rd order (A2 and A3) arterioles in the left cremaster muscle of male Sprague-Dawley rats anesthetized with pentobarbital sodium were measured using videomicroscopy. Adenosine (ADO) at 534 μg intraarterially, topical ADO at 10−3 M, and the endothelium-dependent agonist topical acetylcholine (ACH) at 10−4 M significantly dilated both A2 and A3 arterioles Pre-ENDT and Post-ENDT. Topical tetraethylammonium chloride (TEA) at 1 mM blocked ADO (intraarterially and topical)-induced A2 and A3 arteriolar dilations Pre-ENDT and Post-ENDT. Arteriolar dilation to ACH was maintained Pre-ENDT, but was blocked by TEA in A2 and A3 arterioles Post-ENDT. The endothelium-independent agonist sodium nitro-prusside (10−5 M), when topically applied, caused maximal arteriolar dilation Pre-ENDT and Post-ENDT in the presence of TEA. The data show that vascular smooth muscle KCa channels are a significant factor in ADO-induced relaxation of cremaster microvessels and are not significantly affected by ENDT. The results also suggest that the mechanism for endothelium-dependent ACH vasodilation changes from a non-KCa channel-mediated mechanism Pre-ENDT to a KCa-mediated mechanism Post-ENDT.