Sildenafil augments the beneficial hemodynamic and histopathological effects of amlodipine in nitric oxide-deficient hypertensive rats: role of nitric oxide-cyclic GMP pathway.
Sildenafil augments the beneficial hemodynamic and histopathological effects of amlodipine in nitric oxide-deficient hypertensive rats: role of nitric oxide-cyclic GMP pathway.
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西地那非增强氨氯地平对一氧化氮缺乏的高血压大鼠的有益血流动力学和组织病理学作用：一氧化氮-环 GMP 途径的作用。
DOI：
10.1016/j.phrs.2008.05.003
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发表时间：
2008
影响因子：
9.3
通讯作者：
A. G. E. Din
中科院分区：
文献类型：
--
作者：
M. Aboutabl;M. Raafat;Y. Maklad;S. Kenawy;A. G. E. Din
勃起功能障碍（ED）与心血管疾病的关联是如此普遍。本研究旨在调查西地那非可能产生的影响；用于治疗ED的原型磷酸二酯酶5抑制剂，对原型第三代钙拮抗剂氨氯地平对一氧化氮（NO）缺乏症高血压大鼠的有益血流动力学和组织病理学影响。用n ω-硝基-l-精氨酸甲酯（l-NAME）治疗4周后诱导高血压。将动物分为正常对照组、高血压对照组、氨氯地平治疗组、西地那非治疗组和联合治疗组。l-NAME治疗后2周开始药物治疗，并与l-NAME治疗持续至治疗期结束。在治疗期结束时评估收缩压（SBP）、血浆硝酸盐/亚硝酸盐（NOx）和血浆cGMP水平。主动脉和肾脏的结构改变也被调查。l-NAME治疗可引起收缩压升高、血浆nox和cGMP水平降低以及所研究组织的不良组织学改变。氨氯地平使收缩压正常化，恢复血浆一氧化氮和cGMP水平，改善一氧化氮缺乏大鼠的不良组织学变化。当与西地那非联用时，氨氯地平的血流动力学和组织病理学作用都得到增强，血浆nox和cGMP水平的潜在升高均高于氨氯地平单用。这些结果表明，西地那非增强了氨氯地平对一氧化氮缺乏高血压大鼠血流动力学和组织病理学的有益作用，并通过NO-cGMP途径发挥关键作用。这种药效学相互作用是否存在于其他不具有这种生化紊乱的高血压模型中，值得进一步研究。
The association of erectile dysfunction (ED) with cardiovascular diseases is so common. This study was carried out to investigate possible impact of sildenafil; the prototype phosphodiesterase 5 inhibitor used for treatment of ED, on the beneficial hemodynamic and histopathological effects of the prototype third generation calcium antagonist, amlodipine, in nitric oxide (NO)-deficient hypertensive rats. Hypertension was induced by 4-weeks treatment with Nω-nitro-l-arginine-methyl ester (l-NAME). Animals were allocated into five groups: normal control, hypertensive control, amlodipine-treated group, sildenafil-treated group and combined treatment group. Drug treatment was started 2 weeks after l-NAME and continued together with l-NAME to the end of the treatment period. Systolic blood pressure (SBP), plasma nitrate/nitrite (NOx) and plasma cGMP levels were evaluated at the end of the treatment period. Aortic and renal structural alterations were also investigated. l-NAME treatment caused elevation of SBP, reduction in plasma NOxand cGMP levels as well as adverse histological alterations in the tissues studied. Amlodipine normalized SBP, restored plasma NOxand cGMP levels and ameliorated the adverse histological changes seen in NO-deficient rats. When combined with sildenafil, both hemodynamic and histopathological effects of amlodipine were augmented with an underlying enhanced elevation of both plasma NOxand cGMP levels to statistically higher values than amlodipine alone. These results show that sildenafil augments the beneficial hemodynamic and histopathological effects of amlodipine in NO-deficient hypertensive rats with a pivotal role being played by NO–cGMP pathway. Whether this pharmacodynamic interaction could exist in other models of hypertension that do not share such biochemical derangement warrants further investigations.
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内皮源性舒张因子控制正常大鼠肾脏中的肾血流动力学。
DOI：
10.1681/asn.v16875
发表时间：
1990
期刊：
Journal of the American Society of Nephrology : JASN
影响因子：
--
作者：
Baylis,C;Harton,P;Engels,K
通讯作者：
Engels,K
影响因子：
--
作者：
GARG, UC;HASSID, A
通讯作者：
HASSID, A
影响因子：
20.1
作者：
Pollman, MJ;Yamada, T;Gibbons, GH
通讯作者：
Gibbons, GH
影响因子：
3.5
作者：
Lagoda, Gwen;Jin, Liming;Burnett, Arthur L.
通讯作者：
Burnett, Arthur L.
钙拮抗剂诱导血管舒张的机制。
DOI：
10.1146/annurev.pa.23.040183.002105
发表时间：
1983
影响因子：
12.5
作者：
Cauvin,C;Loutzenhiser,R;VanBreemen,C
通讯作者：
VanBreemen,C