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Systemic inhibition of nitric oxide and prostaglandins in volume-induced natriuresis and hypertension.

机译:一氧化氮和前列腺素在体积诱发性利钠和高血压中的全身抑制作用。

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摘要

Nitric oxide (NO) synthesis inhibition with NG-nitro-L-arginine methyl ester (L-NAME) (10 micrograms.kg-1.min-1 i.v.), cyclooxygenase inhibition with meclofenamate (Meclo; 5 mg/kg i.v. bolus), and combination of drugs (L-NAME + Meclo) were used to investigate the roles of NO and prostaglandins (PG) in the hemodynamic and natriuretic responses to isotonic saline volume expansion (VE; 5% body wt over 60 min) in anesthetized dogs. Before VE, L-NAME (n = 6), Meclo (n = 6), and L-NAME + Meclo (n = 6) produced significant increments in mean arterial pressure (MAP) of 12 +/- 2, 15 +/- 3, and 17 +/- 3 mmHg, respectively. VE did not change MAP in Meclo-treated dogs, but produced a significant elevation in the control dogs (14 +/- 6 mmHg), in L-NAME-treated dogs (17 +/- 6 mmHg), and in dogs pretreated with L-NAME + Meclo (12 +/- 5 mmHg). VE alone induced marked natriuretic responses in the control (38 +/- 9 to 562 +/- 86 mumol/min), L-NAME (31 +/- 9 to 664 +/- 65 mumol/min), and Meclo groups (41 +/- 10 to 699 +/- 51 mumol/min). However, this natriuretic response was attenuated in dogs pretreated with L-NAME + Meclo (12 +/- 4 to 185 +/- 52 mumol/ min). These results indicate that 1) blockade of both NO and PGs has significant diminishing effects on volume-induced natriuresis, 2) NO blockade alone impairs volume-induced natriuresis in a manner that requires further increases in MAP to restore the natriuresis, and 3) PG blockade alone does not curtail volume-induced natriuresis.
机译:NG-硝基-L-精氨酸甲酯(L-NAME)(10微克.kg-1.min-1 iv)对一氧化氮(NO)的合成抑制作用,甲氯芬那酸酯(Meclo; 5 mg / kg iv推注)抑制环氧合酶,并使用药物(L-NAME + Meclo)的组合研究了NO和前列腺素(PG)在麻醉狗对等渗盐水体积膨胀(VE; 60分钟内5%体重)的血流动力学和利尿钠应答中的作用。在VE之前,L-NAME(n = 6),Meclo(n = 6)和L-NAME + Meclo(n = 6)使平均动脉压(MAP)显着增加12 +/- 2、15 + / -3和17 +/- 3 mmHg。在美克洛治疗的狗中,VE并未改变MAP,但在对照狗(14 +/- 6 mmHg),在L-NAME治疗的狗(17 +/- 6 mmHg)和经预先治疗的狗中产生了明显的升高L-NAME + Meclo(12 +/- 5毫米汞柱)。单独的VE在对照组(38 +/- 9至562 +/- 86摩尔/分钟),L-NAME(31 +/- 9至664 +/- 65摩尔/分钟)和Meclo组( 41 +/- 10至699 +/- 51摩尔/分钟)。然而,利尿钠反应在用L-NAME + Meclo预处理的狗中减弱(12 +/- 4至185 +/- 52摩尔/分钟)。这些结果表明,1)对NO和PG的阻滞对体积诱导的利尿有明显的减弱作用; 2)仅对NO的阻滞以需要进一步增加MAP来恢复利尿的方式损害体积诱导的利尿;以及3)PG单独进行封锁并不能减少容量诱发的利尿。

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