Szilvássy Z, Csont T, Páli T, Droy-Lefaix M T, Ferdinandy P
Department of Pharmacology, University of Debrecen, Debrecen, Hungary.
J Vasc Res. 2001 Jan-Feb;38(1):39-46. doi: 10.1159/000051028.
We studied the effect of the furopyridine derivative antihypertensive drug, cicletanine, on blood pressure, vascular nitric oxide (NO) and cyclic guanosine 3':5'-monophosphate (cGMP) content in the aorta and the renal and carotid arteries, aortic superoxide production, and serum nitrotyrosine level in hypertensive/atherosclerotic rabbits. The effect of cicletanine was compared to that of furosemide. Rabbits were fed a normal or a cholesterol-enriched (1.5%) diet over 8 weeks. On the 8th week, the rabbits were treated per os with 2 x 50 mg/kg daily doses of cicletanine, furosemide, or vehicle for 5 days (n = 5-6 in each groups). The cholesterol diet increased mean arterial blood pressure (MABP) from 86 +/- 1 to 94 +/- 2 mm Hg (p < 0.05). Cicletanine decreased MABP in atherosclerotic rabbits to 85 +/- 1 mm Hg (p < 0.05), but it did not affect MABP in normal animals. Furosemide was without effect in both groups. In normal animals, NO content (assessed by electron spin resonance after in vivo spin trapping) in the aorta and the renal and carotid arteries was increased by cicletanine, and the drug increased cGMP in the renal artery as measured by radioimmunoassay. The cholesterol-enriched diet decreased both vascular NO and cGMP and increased aortic superoxide production assessed by lucigenin-enhanced chemiluminescence and serum nitrotyrosine determined by ELISA. In atherosclerotic animals, cicletanine increased NO and cGMP content in the aorta and the renal and carotid arteries and decreased aortic superoxide production and serum nitrotyrosine. Furosemide did not influence these parameters. We conclude that cicletanine lowers blood pressure in hypertensive/atherosclerotic rabbits. The antihypertensive effect of the drug in atherosclerosis may be based on its beneficial effects on the vascular NO-cGMP system and on the formation of reactive oxygen species.
我们研究了呋喃吡啶衍生物降压药西氯他宁对高血压/动脉粥样硬化兔的血压、血管一氧化氮（NO）和主动脉、肾动脉及颈动脉中环磷酸鸟苷（cGMP）含量、主动脉超氧化物生成以及血清硝基酪氨酸水平的影响。将西氯他宁的作用与呋塞米的作用进行了比较。给兔子喂食正常或富含胆固醇（1.5%）的饲料8周。在第8周，给兔子口服每日2次、每次50 mg/kg剂量的西氯他宁、呋塞米或赋形剂，持续5天（每组n = 5 - 6）。胆固醇饮食使平均动脉血压（MABP）从86±1 mmHg升高至94±2 mmHg（p < 0.05）。西氯他宁可使动脉粥样硬化兔的MABP降至85±1 mmHg（p < 0.05），但对正常动物的MABP无影响。呋塞米在两组中均无作用。在正常动物中，西氯他宁可增加主动脉、肾动脉及颈动脉中的NO含量（通过体内自旋捕获后电子自旋共振评估），并且通过放射免疫测定法测得该药物可增加肾动脉中的cGMP。富含胆固醇的饮食会降低血管NO和cGMP，并增加通过光泽精增强化学发光评估的主动脉超氧化物生成以及通过ELISA测定的血清硝基酪氨酸。在动脉粥样硬化动物中，西氯他宁可增加主动脉、肾动脉及颈动脉中的NO和cGMP含量，并降低主动脉超氧化物生成和血清硝基酪氨酸。呋塞米对这些参数无影响。我们得出结论，西氯他宁可降低高血压/动脉粥样硬化兔的血压。该药物在动脉粥样硬化中的降压作用可能基于其对血管NO - cGMP系统以及活性氧形成的有益作用。
