Renoprotective and haemodynamic effects of adiponectin and peroxisome proliferator-activated receptor agonist, pioglitazone, in renal vasculature of diabetic Spontaneously hypertensive rats.
Renoprotective and haemodynamic effects of adiponectin and peroxisome proliferator-activated receptor agonist, pioglitazone, in renal vasculature of diabetic Spontaneously hypertensive rats.
复制标题
DOI：
10.1371/journal.pone.0229803
复制
发表时间：
2020
期刊：
影响因子：
3.7
通讯作者：
Eseyin OA
中科院分区：
文献类型：
--
作者：
Afzal S;Abdul Sattar M;Johns EJ;Eseyin OA
吡格列酮是一种治疗糖尿病的药物，具有完全的PPAR-γ激动剂活性，可增加循环脂联素血浆浓度。高血压肾功能不全患者血浆脂联素水平降低。本研究探讨了吡格列酮单独和联合治疗糖尿病高血压大鼠模型后，肾上腺素能受体激动剂和血管紧张素II的肾脏保护，改变排泄功能和肾脏血流动力学反应。吡格列酮口服给药[10 mg/kg/d]，持续28天，脂联素腹腔注射[2.5μg/kg/d]，持续7天。SHR组接受吡格列酮或脂联素联合治疗。一组Wistar京都大鼠[WKY]作为正常血压对照，而链脲佐菌素给药的SHR作为糖尿病高血压大鼠。在第0、8、21和28天采集代谢数据和血浆样品。在急性研究中，测定了血管紧张素II [ANGII]、去甲肾上腺素[NA]、苯肾上腺素[PE]和甲氧胺[ME]的肾血管收缩作用。糖尿病SHR对照组的基础平均动脉压高于WKY组，RCBP和血浆脂联素低于WKY组，肌酐清除率和尿钠排泄率高于WKY组[均P<0.05]，这些均通过单独药物治疗恢复正常，并且在联合治疗后恢复更大程度。糖尿病SHR对NA、PE、ME和ANGII肾内给药的反应均大于WKY和SHR [P<0.05]。脂联素使糖尿病治疗的SHR对NA、PE、ME和ANG II的反应明显减弱40%，而吡格列酮与脂联素联合治疗进一步减弱对肾上腺素能激动剂的反应65%。[all P <0.05]。这些结果表明，脂联素通过脂联素受体和过氧化物酶体增殖物激活受体-γ（PPAR-γ）对糖尿病SHR具有肾脏保护作用，并改善肾脏血流动力学，提示脂联素与吡格列酮之间存在协同作用。糖尿病SHR肾血管中脂联素受体、过氧化物酶体增殖物激活受体-γ和α肾上腺素受体之间也可能存在相互作用。
Pioglitazone, a therapeutic drug for diabetes, possesses full PPAR-γ agonist activity and increase circulating adiponectin plasma concentration. Plasma adiponectin concentration decreases in hypertensive patients with renal dysfunctions. Present study investigated the reno-protective, altered excretory functions and renal haemodynamic responses to adrenergic agonists and ANG II following separate and combined therapy with pioglitazone in diabetic model of hypertensive rats. Pioglitazone was given orally [10mg/kg/day] for 28 days and adiponectin intraperitoneally [2.5μg/kg/day] for last 7 days. Groups of SHR received either pioglitazone or adiponectin in combination. A group of Wistar Kyoto rats [WKY] served as normotensive controls, whereas streptozotocin administered SHRs served as diabetic hypertensive rats. Metabolic data and plasma samples were taken on day 0, 8, 21 and 28. In acute studies, the renal vasoconstrictor actions of Angiotensin II [ANGII], noradrenaline [NA], phenylephrine [PE] and methoxamine [ME] were determined. Diabetic SHRs control had a higher basal mean arterial blood pressure than the WKY, lower RCBP and plasma adiponectin, higher creatinine clearance and urinary sodium excretion compared to WKY [all P<0.05] which were normalized by the individual drug treatments and to greater degree following combined treatment. Responses to intra-renal administration of NA, PE, ME and ANGII were larger in diabetic SHR than WKY and SHRs [P<0.05]. Adiponectin significantly blunted responses to NA, PE, ME and ANG II in diabetic treated SHRs by 40%, whereas the pioglitazone combined therapy with adiponectin further attenuated the responses to adrenergic agonists by 65%. [all P <0.05]. These findings suggest that adiponectin possesses renoprotective effects and improves renal haemodynamics through adiponectin receptors and PPAR-γ in diabetic SHRs, suggesting that synergism exists between adiponectin and pioglitazone. A cross-talk relationship also supposed to exists between adiponectin receptors, PPAR-γ and alpha adrenoceptors in renal vasculature of diabetic SHRs.
登录
查看更多内容
影响因子：
6.3
作者：
Abdulla, M. H.;Sattar, M. A.;Johns, E. J.
通讯作者：
Johns, E. J.
影响因子：
8.2
作者：
Frystyk, J;Tarnow, L;Flyvbjerg, A
通讯作者：
Flyvbjerg, A
影响因子：
15.9
作者：
ANDERSON, EA;HOFFMAN, RP;MARK, AL
通讯作者：
MARK, AL
影响因子：
3.2
作者：
Adamczak, M;Wiecek, A;Matsuzawa, Y
通讯作者：
Matsuzawa, Y
影响因子：
5
作者：
Abdulla, Mohammed H.;Sattar, Munavvar A.;Johns, Edward J.
通讯作者：
Johns, Edward J.