Sládková M, Kojsová S, Jendeková L, Pechánová O
Institute of Normal and Pathological Physiology, Slovak Academy of Sciences, Bratislava, Slovak Republic.
Physiol Res. 2007;56 Suppl 2:S85-S91. doi: 10.33549/physiolres.931402. Epub 2007 Sep 5.
We aimed to compare the effects of chronic and acute administration of structurally different antihypertensives, diuretics - indapamide and hydrochlorothiazide, ACE inhibitor - captopril and indapamide+captopril combination on endothelium-dependent relaxation of femoral artery isolated from nitric oxide (NO)-deficient rats. In the chronic experiment, femoral artery was isolated from Wistar rats receiving L-NAME (40 mg/kg/day) solely or with indapamide (1 mg/kg/day), hydrochlorothiazide (10 mg/kg/day), captopril (10 mg/kg/day), and indapamide+captopril combination for seven weeks. In the acute in vitro experiment, the incubation medium with femoral artery isolated from L-NAME-hypertensive rats was supplemented with investigated antihypertensives in the same concentration 10(-4) mol/l. Interestingly, chronic L-NAME treatment did not cause a reduction of vasorelaxation. Indapamide+captopril elevated relaxation above the control level and completely prevented blood pressure increase induced by L-NAME. Acute incubation with captopril only or indapamide+captopril improved relaxation of femoral artery isolated from L-NAME-hypertensive rats, while the incubation with all antihypertensives increased vasorelaxation of femoral artery isolated from control Wistar rats. In conclusion, NO might be involved in the indapamide- and hydrochlorothiazide-induced improvement of vasorelaxation, while different vasorelaxing factors (prostacyclin, EDHF) contribute to the captopril-induced improvement of vasorelaxation. During the chronic treatment additive and synergic effects of indapamide and captopril may contribute to the prevention of hypertension and increase of vasorelaxation.
我们旨在比较结构不同的抗高血压药（利尿剂——吲达帕胺和氢氯噻嗪、血管紧张素转换酶抑制剂——卡托普利以及吲达帕胺 + 卡托普利组合）的慢性和急性给药对从一氧化氮（NO）缺乏大鼠分离出的股动脉内皮依赖性舒张的影响。在慢性实验中，从仅接受左旋精氨酸甲酯（L-NAME，40毫克/千克/天）或与吲达帕胺（1毫克/千克/天）、氢氯噻嗪（10毫克/千克/天）、卡托普利（10毫克/千克/天）以及吲达帕胺 + 卡托普利组合共同接受治疗的Wistar大鼠中分离股动脉，持续七周。在急性体外实验中，从L-NAME高血压大鼠分离出的股动脉的孵育培养基中添加相同浓度10⁻⁴摩尔/升的被研究抗高血压药。有趣的是，慢性L-NAME治疗并未导致血管舒张功能降低。吲达帕胺 + 卡托普利使舒张功能提高至对照水平以上，并完全防止了L-NAME诱导的血压升高。仅与卡托普利或吲达帕胺 + 卡托普利进行急性孵育可改善从L-NAME高血压大鼠分离出的股动脉的舒张功能，而与所有抗高血压药孵育则增加了从对照Wistar大鼠分离出的股动脉的血管舒张功能。总之，NO可能参与了吲达帕胺和氢氯噻嗪诱导的血管舒张改善过程，而不同的血管舒张因子（前列环素、内皮依赖性超极化因子）促成了卡托普利诱导的血管舒张改善。在慢性治疗期间，吲达帕胺和卡托普利的相加和协同作用可能有助于预防高血压和增加血管舒张功能。
