NO and K(ATP) channels underlie endotoxin-induced smooth muscle hyperpolarization in rat mesenteric resistance arteries

1. Smooth muscle membrane potential and tension measurements were made in isolated mesenteric resistance arteries from rats exposed to bacterial endotoxin (lipopolysaccharide, LPS; 10 mg kg(−1), i.p.) for 3 h to mimic septic shock syndrome. 2. Over this period, rats developed an endotoxaemic response, assessed in vivo as a 41±4 mmHg drop in mean blood pressure, vascular hyporeactivity to noradrenaline (1 μg kg(−1), i.v.) and a significant increase in core body temperature. 3. In mesenteric small resistance arteries from these rats (o.d. 180 – 240 μm), phenylephrine (0.01–3 μM)-evoked contraction was not altered when compared with arteries from sham-operated animals, but the concentration–relaxation curve to acetylcholine (ACh; 0.01 – 3 μM) displayed a small, but significant, shift to the right. 4. The smooth muscle resting membrane potential (−70.3±1.6 mV) in arteries from LPS-treated rats was significantly greater than in control arteries (−55.4±1.2 mV), but in both cases the smooth muscle was depolarized to a similar potential by the application of N(ω)-nitro-L-arginine methyl ester (L-NAME; 0.3 mM; −54.1±2.3 vs −52.4±2.5 mV) or glibenclamide (10 μM; −55.0±2.1 vs −50.4±2.0 mV). 5. ACh (1 μM) elicited a maximal hyperpolarization, which ranged from −14.7±3.2 mV (in arteries from LPS-treated rats) to –20.6±2.4 mV (in arteries from sham-operated rats), and was not altered by the presence of L-NAME. Levcromakalim (1 μM) increased the smooth muscle membrane potential by around −24 mV in arteries from both sets of experimental animals. 6. These results indicate that at the level of the resistance vasculature, endotoxaemia is associated with pronounced smooth muscle hyperpolarization reflecting the action of NO on K(ATP) channels. These changes were not associated with vascular hyporeactivity or depressed endothelial cell function in vitro, suggesting that mesenteric resistance arteries may not contribute to equivalent changes in vivo