Pargger H, Kaufmann M A, Drop L J
Department of Anesthesia & Critical Care, Massachusetts General Hospital, Boston 02114, USA.
Intensive Care Med. 1998 Jan;24(1):61-70. doi: 10.1007/s001340050516.
Calcium may be indicated in critically ill patients for hemodynamic support. Its well-known action includes peripheral vasoconstriction. Vascular effects of calcium are unknown, however, in the presence of hypertension or in combination with calcium channel blocking drugs, commonly prescribed in the treatment of hypertension. The renal vessels of the spontaneously hypertensive rat (SHR) represent a suitable study model, because their vascular reactivity closely agrees with that in hypertensive humans. The present study should clarify (a) are the renal vessels of SHR responsive to high and low ionized calcium ([Ca+2] within the clinical ranges? (b) because release of nitric oxide is calcium ion dependent, are renal vascular responses altered after inhibition of NO synthase? (c) are vascular responses of SHR to hypercalcemia altered by the calcium channel blocking drug verapamil?
We compared isolated kidneys of SHR and those of two strains of age-matched normotensive rats (NTR) in their responses to high and low [Ca+2]. They were perfused with oxygenated, warmed (37 degrees C) albumin containing Krebs-Henseleit buffer. In protocol A (n = 8 for each rat strain) steady state high [Ca+2] (1.88 mmol/l) and low [Ca+2] (0.55 mmol/l) were instituted in randomized order. In protocol B (n = 8 for each rat strain) interventions identical to those of protocol A were instituted after inhibition of NO synthase with NG monomethyl-L-arginine (L-NMMA). In protocol C, high and low [Ca+2] levels were instituted in SHR after verapamil pretreatment. At each [Ca+2] we measured changes in renal flow at constant perfusion pressures of 100 and 150 mm Hg.
In SHR (perfusion pressure 100 mm Hg), high [Ca+2] induced a decrease in renal flow (-11.8 +/- 1.8% of control), which was significantly greater (p < 0.05) than the change (-6.1 +/- 1.5 and -6.9 +/- 1.4% of control) recorded in the two normotensive strains. In SHR (perfusion pressure 150 mmHg), high [Ca+2] induced a decrease in renal flow (-12 +/- 1.3% of control), also significantly greater (p < 0.05) than the changes (-6.2 +/- 1.1 and -5.8 +/- 1.7% of control) in the two normotensive strains. Similar differences and significances were again observed after L-NMMA pretreatment. In SHR, verapamil prevented renal vascular responses in SHR to both high and low [Ca+2].
First, renal vascular responses to high [Ca+2] in SHR are exaggerated. At the upper end of the hypercalcemia range the observed changes in renal flow at constant perfusion pressure were modest, however, and with lesser degrees of hypercalcemia they may be anticipated to be even less pronounced. Second, effects of high [Ca+2] were abolished after verapamil. If these findings are clinically applicable, they are of interest when calcium is infused in patients with hypertension.
在危重症患者中，钙可用于血流动力学支持。其众所周知的作用包括外周血管收缩。然而，在高血压患者中或与治疗高血压常用的钙通道阻滞剂联合使用时，钙对血管的影响尚不清楚。自发性高血压大鼠（SHR）的肾血管是一个合适的研究模型，因为其血管反应性与高血压患者的血管反应性非常相似。本研究旨在阐明：（a）SHR的肾血管对临床范围内的高、低离子钙（[Ca+2]）是否有反应？（b）由于一氧化氮的释放依赖于钙离子，抑制一氧化氮合酶后肾血管反应是否会改变？（c）钙通道阻滞剂维拉帕米是否会改变SHR对高钙血症的血管反应？
我们比较了SHR和两株年龄匹配的正常血压大鼠（NTR）的离体肾脏对高、低[Ca+2]的反应。用含 Krebs-Henseleit 缓冲液的氧合、加温（37℃）白蛋白对其进行灌注。在方案A中（每种大鼠品系n = 8），以随机顺序设置稳态高[Ca+2]（1.88 mmol/l）和低[Ca+2]（0.55 mmol/l）。在方案B中（每种大鼠品系n = 8），用NG-单甲基-L-精氨酸（L-NMMA）抑制一氧化氮合酶后，进行与方案A相同的干预。在方案C中，维拉帕米预处理后在SHR中设置高、低[Ca+2]水平。在每个[Ca+2]水平，我们在100和150 mmHg的恒定灌注压力下测量肾血流量的变化。
在SHR（灌注压力100 mmHg）中，高[Ca+2]导致肾血流量减少（-11.8±1.8%对照值），这明显大于（p < 0.05）两株正常血压品系中记录的变化（-6.1±1.5%和-6.9±1.4%对照值）。在SHR（灌注压力150 mmHg）中，高[Ca+2]导致肾血流量减少（-12±1.3%对照值），同样明显大于（p < 0.05）两株正常血压品系中的变化（-6.2±1.1%和-5.8±1.7%对照值）。L-NMMA预处理后再次观察到类似的差异和显著性。在SHR中，维拉帕米可防止SHR对高、低[Ca+2]的肾血管反应。
首先，SHR对高[Ca+2]的肾血管反应增强。然而，在高钙血症范围的上限，在恒定灌注压力下观察到的肾血流量变化较小，并且在高钙血症程度较轻时，预计变化会更小。其次，维拉帕米后高[Ca+2]的作用被消除。如果这些发现具有临床适用性，那么在给高血压患者输注钙时它们是有意义的。
