Suzuki H, Ikezaki H, Hong D, Rubinstein I
Department of Medicine, University of Illinois at Chicago, 60612-7323, USA.
J Appl Physiol (1985). 2000 Jun;88(6):1983-8. doi: 10.1152/jappl.2000.88.6.1983.
The purpose of this study was to determine whether activation of prostaglandin H(2)-thromboxane A(2) (PGH(2)-TxA(2)) receptors impedes vasodilation in the in situ peripheral microcirculation of spontaneously hypertensive hamsters, a new rodent model of high-renin genetic hypertension. Using intravital microscopy, we found that vasodilation elicited by suffusion of acetylcholine and vasoactive intestinal peptide (VIP), two neurotransmitters localized in perivascular nerves in the peripheral circulation, on the in situ cheek pouch was significantly attenuated in spontaneously hypertensive hamsters relative to age- and genetically matched normotensive hamsters (P < 0.05). However, nitroglycerin-induced vasodilation was similar in both groups. Pretreatment with SQ-29548, a selective and potent PGH(2)-TxA(2)-receptor antagonist, restored acetylcholine- and VIP-induced vasodilation in spontaneously hypertensive hamsters. SQ-29548 had no significant effects on resting arteriolar diameter and on nitroglycerin-induced vasodilation in both groups. SQ-29548 slightly but significantly potentiated VIP- but not acetylcholine-induced vasodilation in normotensive hamsters. Collectively, these data indicate that activation of PGH(2)-TxA(2) receptors impedes agonist-induced vasodilation in the in situ cheek pouch of spontaneously hypertensive hamsters. We suggest that this model is suitable for studying the role of prostanoids in mediating vasomotor dysfunction observed in genetic hypertension.
本研究的目的是确定前列腺素H2-血栓素A2（PGH2-TxA2）受体的激活是否会阻碍自发性高血压仓鼠（一种新的高肾素遗传性高血压啮齿动物模型）原位外周微循环中的血管舒张。使用活体显微镜，我们发现，相对于年龄和基因匹配的正常血压仓鼠，乙酰胆碱和血管活性肠肽（VIP，两种存在于外周循环血管周围神经中的神经递质）灌注引起的原位颊囊血管舒张在自发性高血压仓鼠中显著减弱（P < 0.05）。然而，两组中硝酸甘油诱导的血管舒张相似。用选择性强效PGH2-TxA2受体拮抗剂SQ-29548预处理可恢复自发性高血压仓鼠中乙酰胆碱和VIP诱导的血管舒张。SQ-29548对两组的静息小动脉直径和硝酸甘油诱导的血管舒张均无显著影响。SQ-29548略微但显著增强了正常血压仓鼠中VIP诱导的血管舒张，但对乙酰胆碱诱导的血管舒张无此作用。总体而言，这些数据表明PGH2-TxA2受体的激活会阻碍自发性高血压仓鼠原位颊囊中激动剂诱导的血管舒张。我们认为该模型适用于研究前列腺素在介导遗传性高血压中观察到的血管舒缩功能障碍中的作用。
