Departamento de Fisiologia e Farmacologia, Centro de Ciências Biológicas, Universidade Federal de Pernambuco, Recife, Brazil.
Eur J Pharmacol. 2011 Mar 11;654(3):280-8. doi: 10.1016/j.ejphar.2011.01.007. Epub 2011 Jan 22.
This study analyzed the effect of aldosterone (0.05mg/kg per day, 3 weeks) on vasoconstriction induced by noradrenaline in mesenteric resistance arteries from WKY rats and SHR. Contraction to noradrenaline was measured in mesenteric resistance arteries from untreated and aldosterone-treatedrats from both strains. Participation of nitric oxide (NO), superoxide anions, thromboxane A(2) (TxA(2)) and prostacyclin in this response was determined. 6-keto-prostaglandin (PG)F1alpha and thromboxane B(2) (TxB(2)) releases were determined by enzyme immunoassay. NO and superoxide anion release were also determined by fluorescence and chemiluminiscence, respectively. Aldosterone did not modify noradrenaline-induced contraction in either strain. In mesenteric resistance arteries from both aldosterone-treated groups, endothelium removal or preincubation with NO synthesis inhibitor L-NAME increased the noradrenaline-induced contraction, while incubation with the superoxide anion scavenger tempol decreased it. Preincubation with either the COX-1/2 or COX-2 inhibitor (indomethacin and NS-398, respectively) decreased the noradrenaline contraction in aldosterone-treated animals, while this response was not modified by COX-1 inhibitor SC-560. TxA(2) synthesis inhibitor (furegrelate), or TxA2 receptor antagonist (SQ 29 548) also decreased the noradrenaline contraction in aldosterone-treated animals. In untreated SHR, but not WKY rats, this response was increased by L-NAME, and reduced by tempol, indomethacin, NS-398 or SQ 29 548. Aldosterone treatment did not modify NO or TxB(2) release, but it did increase superoxide anion and 6-keto-PGF(1alpha) release in mesenteric resistance arteries from both strains. In conclusion, chronic aldosterone treatment reduces smooth muscle contraction to alpha-adrenergic stimuli, producing a new balance in the release of endothelium-derived prostanoids and NO.
这项研究分析了醛固酮（每天 0.05mg/kg，持续 3 周）对 WKY 大鼠和 SHR 肠系膜阻力动脉中去甲肾上腺素诱导的血管收缩的影响。在未处理和醛固酮处理的两种品系大鼠的肠系膜阻力动脉中测量去甲肾上腺素引起的收缩。确定了一氧化氮（NO）、超氧阴离子、血栓素 A2（TxA2）和前列环素在这种反应中的参与。通过酶免疫测定法测定 6-酮-前列腺素（PG）F1alpha 和血栓烷 B2（TxB2）的释放。还通过荧光和化学发光分别测定 NO 和超氧阴离子的释放。醛固酮在两种品系中均不改变去甲肾上腺素诱导的收缩。在来自两种醛固酮处理组的肠系膜阻力动脉中，内皮去除或预先用 NO 合成抑制剂 L-NAME 孵育增加了去甲肾上腺素诱导的收缩，而用超氧阴离子清除剂 Tempo 孵育则降低了收缩。用 COX-1/2 或 COX-2 抑制剂（吲哚美辛和 NS-398）预孵育可降低醛固酮处理动物的去甲肾上腺素收缩，而 COX-1 抑制剂 SC-560 则不改变这种反应。TxA2 合成抑制剂（furegrelate）或 TxA2 受体拮抗剂（SQ 29548）也降低了醛固酮处理动物的去甲肾上腺素收缩。在未处理的 SHR 中，但在 WKY 大鼠中，这种反应被 L-NAME 增加，被 Tempo、吲哚美辛、NS-398 或 SQ 29548 减少。醛固酮处理不改变 NO 或 TxB2 的释放，但确实增加了两种品系的肠系膜阻力动脉中超氧阴离子和 6-酮-PGF1alpha 的释放。总之，慢性醛固酮处理降低了平滑肌对 α-肾上腺素能刺激的收缩反应，导致内皮衍生的前列腺素和 NO 释放的新平衡。
