Roles of atrial natriuretic factors in rats experimental models of hypertension, renal failure and heart failure

心房钠尿因子在大鼠高血压、肾衰竭、心力衰竭模型中的作用

• 批准号: 62570376
• 负责人: YASUJIMA Minoru
• 金额: $ 1.22万
• 依托单位: Tohoku University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1987
• 资助国家: 日本
• 起止时间: 1987 至 1989
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-62570376/
• 关键词: Atrial natriuretic Factor (ANF); Hypertension; Renal failure; Heart failure; Cyclic GMP; Natriuresis; Vasodilatation; 心房性Na利尿ホルモン; 食塩依存性高血圧ラット; 腎摘除腎不全ラット; 心房性Na利尿因子(ANF); cycle nucleotides; 単離尿細管; 培養血管平滑筋細胞; 腎摘除腎不全モデルラット; DOCA食塩高血圧ラット; 高血圧

To assess the pathophysiological roles of atrial natriuretic factor (ANF) in hypertension, renal failure and heart failure, we determined circulating levels of ANF and the effects of synthetic ANF in rats experimental model of hypertension, chronic renal failure or chronic heart failure. We also examined the effects of synthetic ANF on cyclic GMP production in rat cultured vascular smooth muscle (VSM), glomerular mesangium (GM) and renal papillary collecting tubule (RPCT) cells to elucidate the mechanisms of vascular and renal actions of ANF. Elevated levels of circulating ANF were observed in spontaneously hypertensive rats (SHR) and DOCA- or aldosterone-salt hypertensive rats compared to control rats, respectively. The sustained infusion of synthetic ANF at a rate of subdepressor dose attenuated the hypertension in DOCA- or aldosterone-salt hypertension, but not in SHR. Circulating levels of ANF were also elevated in SHK or Wistar Kyoto rats remnant kidney model of chronic renal fail … More ure and in rats with chronic heart failure, induced by ligation of left coronary artery compared to control animals, respectively. In SHR with renal ablation, the sustained infusion of synthetic ANF induced a significant reduction of blood pressure, and the impaired renal function ameliorated. Angiotensin converting enzyme inhibitors also ameliorated renal function, which was associated with the decrease in circulating levels of ANF. In rats with chronic heart failure, the responses of natriuresis and diuresis to graded dosed of synthetic ANF were attenuated compared to control rats. In vitro studies, synthetic ANF increased cyclic GMP levels dose-dependently in cultured cells from rat renal and mesenteric VSM, GM and RPCT. The sensitivity of VSM and GM cells to synthetic ANF were greater than that RPCT cells.These results suggest that ANF may play the protective roles in the pathophysioloqy of hypertension, chronic renal failure and chronic heart failure via its vascular and renal action. Less

为探讨心钠素（ANF）在高血压、慢性肾功能衰竭和心力衰竭中的病理生理作用，本研究测定了高血压、慢性肾功能衰竭和慢性心力衰竭大鼠模型循环中ANF的水平，并观察了合成ANF对高血压、慢性肾功能衰竭和慢性心力衰竭的影响。我们还研究了合成的ANF对培养的大鼠血管平滑肌（VSM）、肾小球系膜（GM）和肾乳头状集合管（RPCT）细胞产生环GMP的影响，以阐明ANF的血管和肾脏作用机制。与对照组大鼠相比，在自发性高血压大鼠（SHR）和DOCA或醛固酮盐高血压大鼠中分别观察到循环心钠素水平升高。持续输注合成心钠素在降压剂量率衰减DOCA或醛固酮盐高血压，但不是在SHR的高血压。慢性肾衰竭的SHK或Wistar京都大鼠残肾模型中循环ANF水平也升高 ...更多信息 与对照动物相比，在通过结扎左冠状动脉诱导的慢性心力衰竭大鼠中，分别为ure和。在SHR肾消融术中，持续输注合成ANF可显著降低血压，并改善受损的肾功能。血管紧张素转换酶抑制剂还改善肾功能，这与循环ANF水平的降低有关。在慢性心力衰竭大鼠中，与对照大鼠相比，对分级剂量的合成ANF的利钠和利尿反应减弱。在体外研究中，合成ANF增加大鼠肾和肠系膜VSM，GM和RPCT培养细胞中的环GMP水平呈剂量依赖性。VSM和GM细胞对合成ANF的敏感性高于RPCT细胞，提示ANF可能通过其血管和肾脏作用在高血压、慢性肾功能衰竭和慢性心力衰竭的病理生理过程中发挥保护作用。少

项目成果

Minoru Yasujima et al.: "Chronic effect of synthetic atrial natriuretic factor in rats made hypertensive by sustained infusion of vasopressin" Biologically Active Atrial Peptides Vol.1 edited by B.M.Brenner and J.H.Laragh,Raven Press,New York. 519-523 (19

Minoru Yasujima 等人：“合成心房钠尿因子对持续输注加压素导致高血压的大鼠的慢性影响”生物活性心房肽第 1 卷，由 B.M.Brenner 和 J.H.Laragh 编辑，Raven Press，纽约。

Minoru Yasujima et al.: "Effects of antihypertensive drugs on renal function and atrial natriuretic polypeptide in spontaneously hypertensive rats with renal ablation." Tohoku J.Exp.Med.158. 85-94 (1989)

Minoru Yasujima 等人：“抗高血压药物对肾脏消融的自发性高血压大鼠肾功能和心房钠尿多肽的影响。”

Minoru Yasujima, et al.: "Effects of chronically administered atrial natriuretic factor in aldosterone-infused hypertensive rats" Jap. Circ. J. 52:1446-1449, 1988.

Minoru Yasujima 等人：“长期施用心房钠尿因子对醛固酮输注的高血压大鼠的影响”Jap。

Minoru Yasujima et al.: "Calcium channel blockers reverse the sustained elevation of blood pressure induced by chronic infusion of endothelin in conscious rats." Am.J.Hypertension. 3. (1990)

Minoru Yasujima 等人：“钙通道阻滞剂可逆转清醒大鼠因长期输注内皮素而引起的血压持续升高。”

Minoru Yasujima et al.: "Effects of chronically administered atrial natriuretic factor in aldosterone-infused hypertensive rats" Jap.Circ.J.52. 1446-1449 (1988)

Minoru Yasujima 等人：“长期施用心房钠尿因子对醛固酮输注的高血压大鼠的影响”Jap.Circ.J.52。