Quantitative analysis of the association between interleukin-10 1082A/G polymorphism and susceptibility to sepsis.

There are some epidemiological studies investigating the association between interleukin-10 (IL-10) 1082A/G polymorphism and sepsis susceptibility reporting conflicting findings. Our work tried to further quantitatively assess the association of the IL-10 1082A/G polymorphism with sepsis susceptibility through a systematic review and meta-analysis. A total of eleven studies with 2,528 subjects were finally included into the meta-analysis. Pooled odds ratios (ORs) and corresponding 95 % confidence intervals (95 % CIs) were calculated with random-effects model or fixed-effects model based on the heterogeneity among the included studies. Meta-analysis of all 11 studies showed that there was an obvious association between IL-10 1082A/G polymorphism and sepsis susceptibility under the allele comparison model (G vs A) and the codominant model (GG vs AA) (for G vs A: OR = 0.83, 95 % CI 0.72-0.96, P = 0.011; for GG vs AA: OR = 0.67, 95 % CI 0.47-0.96, P = 0.029). Subgroup analysis by ethnicity showed that there was an obvious association between IL-10-1082A/G polymorphism and sepsis susceptibility in Asians under three comparison models (for G vs A: OR = 0.75, 95 % CI 0.62-0.91, P = 0.004; for GG vs AA: OR = 0.39, 95 % CI 0.21-0.73, P = 0.003; for GG vs AA/AG: OR = 0.36, 95 % CI 0.14-0.92, P = 0.032), but there was no similar association in Caucasians under all four comparison models. Our meta-analysis reveals that the IL-10-1082A/G polymorphism has an association with the susceptibility to sepsis in Asian populations. Further studies are needed to investigate the effect of IL-10-1082A/G polymorphism on sepsis susceptibility in Caucasians.

Role of potassium channels in regulation of rat coronary arteriole tone.

Activity of potassium (K(+)) channels plays a key role in regulating arterial tone and therefore blood flow. But little is known about the roles of K(+) channels in the coronary arterioles. The aim of the present study was to investigate the influences of several potassium channel blockers on resting vascular tone in isolated rat coronary arteriole. The coronary arterioles were carefully dissected, cannulated and pressurized. The inner diameter of vessels was recorded by a computerized diameter tracking system and the effects of K(+) channels on the development of vascular myogenic tone was tested by application of various K(+) channel inhibitors. Inhibition of voltage-dependent K(+) (K(V)) channels and inward rectifier K(+) (K(ir)) channels significantly increased the tone constriction. But inhibition of Ca(2+)-activated K(+) (K(Ca)) channels and ATP-sensitive K(+) (K(ATP)) channels had no effect on the resting tone. In addition, inhibition of nitric oxide synthase (NOS) further decreased the tone diameter. Combined inhibition of K(V), K(ir) and NOS induced the strongest tone constriction. Our results suggested that activity of K(V) and K(ir) channels, and basal nitric oxide (NO) contribute to the myogenic tone in rat coronary arteriole under resting conditions, but basal NO may not contribute to the activation of K(V) and K(ir) channels. K(Ca) and K(ATP) channels are likely to have a very low open probability under normal conditions.

Tanshinone II(A) elicited vasodilation in rat coronary arteriole: roles of nitric oxide and potassium channels.

Salvia miltiorrhiza has been widely used in the treatment of various cardiovascular diseases due to its ability to improve coronary microcirculation and increase coronary blood flow. Tanshinone II(A), the major active lipophilic ingredient responsible for the beneficial actions of Salvia miltiorrhiza, was shown to induce vasodilation in coronary arteries. But its effects on coronary arterioles remain unknown. The purpose of this study was to investigate the effects of tanshinone II(A) on isolated rat coronary arteriole and the underlying mechanisms. Coronary arterioles were carefully dissected, cannulated and pressurized. Tanshinone II(A)-elicited vascular inner diameter change was recorded by a computerized diameter tracking system. To investigate the mechanisms governing the vasodilative effects of tanshinone II(A), the roles of endothelium, endothelium-derived vasoactive factors and potassium channels were assessed respectively. Endothelium denudation, inhibition of nitric oxide synthase (NOS), inhibition of the cytochrome P450 epoxygenase, and blockade of the large conductance calcium(Ca(2+))-activated potassium channels (BKca) significantly decreased the vasodilation elicited by Tanshinone II(A). The results indicated that tanshinone II(A) induces an endothelium-dependent vasodilation in coronary arterioles; nitric oxide (NO) and cytochrome P450 metabolites contribute to the vasodilation; activation of BKca channels plays an important role in the vasodilation.