Chen Horng H, Cataliotti Alessandro, Schirger John A, Martin Fernando L, Harstad Lynn K, Burnett John C
Department of Internal Medicine, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA.
J Am Coll Cardiol. 2009 Apr 14;53(15):1302-8. doi: 10.1016/j.jacc.2009.01.030.
The purpose of this study was to test the hypothesis that local renal delivery of B-type natriuretic peptide (BNP) will overcome renal resistance to BNP without systemic hypotension.
BNP has vasodilating, natriuretic, and renin-inhibiting properties. In overt heart failure (HF), there is development of renal resistance to BNP.
We defined the cardiorenal and humoral effects of systemic (n = 6) or local renal (n = 7) administration of canine BNP (0.01 microg/kg/min) in 2 separate groups of dogs with pacing-induced subacute overt HF complicated by renal dysfunction. We used a commercially available small (3.1-F) bifurcated renal catheter (FlowMedica Inc., Fremont, California) for direct bilateral infusion of BNP into both renal arteries.
With systemic BNP at this clinically used dose (without the bolus), urine flow increased, but there was only a trend for an increase in urinary sodium excretion and glomerular filtration rate (GFR). In contrast, local renal delivery of BNP resulted in significant diuresis and natriuresis and an increase in GFR. These diuretic and natriuretic responses were greater with local renal BNP compared with systemic BNP, and were associated with increased delivery of BNP to the renal tubules as evident by a greater urinary BNP excretion resulting in a decrease in distal reabsorption of sodium. Importantly, local renal BNP did not result in a significant decrease in mean arterial pressure that was observed with systemic BNP.
We conclude that local renal BNP delivery is a novel strategy that may overcome renal assistance to BNP in overt HF by increasing local delivery of BNP to the renal tubules.
本研究旨在验证以下假设，即局部肾脏递送B型利钠肽（BNP）可克服肾脏对BNP的抵抗，且不会引起全身性低血压。
BNP具有血管舒张、利钠和抑制肾素的特性。在明显心力衰竭（HF）中，会出现肾脏对BNP的抵抗。
我们在两组因起搏诱发亚急性明显HF并伴有肾功能不全的犬中，分别定义了全身性（n = 6）或局部肾脏（n = 7）给予犬BNP（0.01μg/kg/分钟）的心脏肾脏和体液效应。我们使用市售的小型（3.1F）分叉肾导管（FlowMedica公司，加利福尼亚州弗里蒙特）将BNP直接双侧注入双侧肾动脉。
使用该临床常用剂量（无推注）的全身性BNP时，尿流量增加，但尿钠排泄和肾小球滤过率（GFR）仅呈增加趋势。相比之下，局部肾脏递送BNP导致显著的利尿和利钠作用以及GFR增加。与全身性BNP相比，局部肾脏BNP的这些利尿和利钠反应更大，并且与BNP向肾小管的递送增加有关，这可通过尿BNP排泄增加导致远端钠重吸收减少来证明。重要的是，局部肾脏BNP不会导致全身性BNP所观察到的平均动脉压显著降低。
我们得出结论，局部肾脏递送BNP是一种新策略，可能通过增加BNP向肾小管的局部递送，克服明显HF中肾脏对BNP的抵抗。
