Grześk Grzegorz, Szadujkis-Szadurski Leszek
Department of Pharmacology and Therapeutics, L. Rydygier Medical University of Bydgoszcz, M. Skłodowskiej-Curie 9, PL 85-094 Bydgoszcz, Poland.
Pol J Pharmacol. 2003 Sep-Oct;55(5):753-62.
The inhibitory effect of lipopolysaccharides (LPS) on alpha-adrenergic contraction is quite well known, but molecular mechanism of this inhibition is unclear. In the present study, the interaction between alpha-adrenoceptor and vasopressin receptor response, and LPS in rat tail artery was investigated using chemical stimulation. In the presence of LPS, noradrenaline, phenylephrine and arginine-vasopressin, concentration-response curves (CRCs) were shifted to the right with the change in maximal responses. The K(A) and K(B) values calculated in the presence and absence of LPS did not differ significantly. The results strongly suggest that LPS did not change the receptors affinity. The changes in the relationship between receptor occupancy and response to an agonist in the presence of LPS and reduction of K(A)/ED(50) value suggest reduction of receptor reserve. In the presence of angiotensin II (Ang II), CRCs were shifted to the right with significant increase in receptor reserve. Moreover, this effect was still present in LPS-pretreated arteries. The receptor reserve reduced by LPS significantly increased in the presence of Ang II. It suggests that inhibitory effect of LPS is partially reversible. The results strongly suggest that in early endotoxemia, inhibitory effect of LPS may by partially reverted by an increase in activity of renin-angiotensin-aldosterone system.
脂多糖（LPS）对α-肾上腺素能收缩的抑制作用已广为人知，但其抑制的分子机制尚不清楚。在本研究中，利用化学刺激研究了大鼠尾动脉中α-肾上腺素能受体与血管加压素受体反应以及LPS之间的相互作用。在存在LPS、去甲肾上腺素、苯肾上腺素和精氨酸血管加压素的情况下，浓度-反应曲线（CRCs）向右移动，最大反应发生变化。在有和没有LPS的情况下计算出的K(A)和K(B)值没有显著差异。结果强烈表明LPS没有改变受体亲和力。在存在LPS的情况下，受体占有率与对激动剂反应之间关系的变化以及K(A)/ED(50)值的降低表明受体储备减少。在存在血管紧张素II（Ang II）的情况下，CRCs向右移动，受体储备显著增加。此外，这种效应在LPS预处理的动脉中仍然存在。在存在Ang II的情况下，LPS显著降低的受体储备明显增加。这表明LPS的抑制作用部分是可逆的。结果强烈表明，在内毒素血症早期，LPS的抑制作用可能会因肾素-血管紧张素-醛固酮系统活性的增加而部分逆转。
