Crumb C K, Martinez-Maldonado M, Eknoyan G, Suki W N
J Clin Invest. 1974 Dec;54(6):1287-94. doi: 10.1172/JCI107874.
The role of parathyroid hormone (PTH) and of Ca(++) in the regulation of bicarbonate absorption (RHCO(3)) and its response to extracellular volume expansion (VE) was studied in HCO(3) (-)-loaded dogs.VE lowered RHCO(3) in both intact (from 24.8 to 22.0 mmol/liter GFR, P < 0.01) and thyroparathyroid-ectomized (TPTX) (from 24.5 to 18.0 mmol/liter GFR, P < 0.001) dogs; glomerular filtration rate (GFR) and filtered HCO(3) (-) did not change. Both groups showed a significant increase in the fractional excretion of sodium (C(Na) x 100/GFR), calcium (C(Ca) x 100/GFR), and chloride (C(Cl) x 100/GFR) and a decrease in phosphorus reabsorption. Fractional clearance of phosphate (C(P) x 100/GFR) rose in both groups but did not achieve significance. Infusion of purified parathyroid extract (PTE) decreased RHCO(3) in intact dogs (from 24.6 to 22.5 mmol/liter GFR, P < 0.025) and in TPTX dogs (from 26.9 to 22.6 mmol/liter GFR, P < 0.05). No change was noted in GFR, renal blood flow (RBF), filtered HCO(3) (-), or fractional excretion of sodium, calcium, or chloride in either group. There was a significant increase in fractional phosphorus clearance and a decrease in phosphorus reabsorption in each group. Infusion of Ca(++) raised ultrafilterable Ca(++) from 5.7 to 7.9 mg/100 ml in intact and from 4.9 to 7.2 mg/100 ml in TPTX dogs; RHCO(3) increased in intact (from 22.9 to 26.9 mmol/liter GFR, P < 0.025) and in TPTX dogs (from 26.6 to 28.6 mmol/liter GFR, P < 0.05). The GFR, RBF, and the fractional excretion of sodium, chloride, and calcium did not change in either group. The reabsorbed phosphate increased in both groups, and fractional phosphorus clearance fell in the intact group but did not change significantly in the TPTX group. Superimposition of PTE on hypercalcemia in TPTX dogs resulted in a decrease in RHCO(3) (from 27.3 to 23.9 mmol/liter GFR, P < 0.001), which was accompanied by an increase in the fractional excretion of phosphate and a decrease in the reabsorbed phosphate. In this group of TPTX dogs hypercalcemia caused a drop in RBF from 135.6 to 105.8 ml/min with no change in GFR. The RBF returned to control value with PTE infusion. IT IS CONCLUDED THAT: (a) the lowering of RHCO(3) by VE is not dependent solely on stimulation of PTH by the lowered Ca(++), (b) PTE acts directly on the renal tubules to lower RHCO(3), (c) Ca(++) enhances RHCO(3) and this effect is exerted in the absence of PTH and calcitonin, (d) neither the effects of Ca(++) nor of PTH appear to be mediated by altered hemodynamics, although this cannot be excluded in Ca(++)-infused TPTX dogs, (e) Ca(++) enhanced phosphate reabsorption in the absence of PTH; this may be a specific effect of hypercalcemia on phosphate reabsorption or the nonspecific consequence of the rise in serum phosphorus.
在碳酸氢根负荷的犬中研究了甲状旁腺激素(PTH)和钙离子(Ca(++))在调节碳酸氢根重吸收(RHCO(3))及其对细胞外液量扩张(VE)反应中的作用。VE使完整犬(肾小球滤过率(GFR)从24.8降至22.0 mmol/升,P < 0.01)和甲状腺甲状旁腺切除(TPTX)犬(GFR从24.5降至18.0 mmol/升,P < 0.001)的RHCO(3)均降低;肾小球滤过率(GFR)和滤过的碳酸氢根(HCO(3) (-))未改变。两组的钠(C(Na)×100/GFR)、钙(C(Ca)×100/GFR)和氯(C(Cl)×100/GFR)分数排泄均显著增加,磷重吸收减少。两组的磷酸盐分数清除率(C(P)×100/GFR)均升高,但未达到显著水平。输注纯化的甲状旁腺提取物(PTE)使完整犬(GFR从24.6降至22.5 mmol/升,P < 0.025)和TPTX犬(GFR从26.9降至22.6 mmol/升,P < 0.05)的RHCO(3)降低。两组的GFR、肾血流量(RBF)、滤过的HCO(3) (-)或钠、钙或氯的分数排泄均无变化。每组的磷酸盐分数清除率显著增加,磷重吸收减少。输注Ca(++)使完整犬的超滤性Ca(++)从5.7升至7.9 mg/100 ml,TPTX犬从4.9升至7.2 mg/100 ml;完整犬(GFR从22.9升至26.9 mmol/升,P < 0.025)和TPTX犬(GFR从26.6升至28.6 mmol/升,P < 0.05)的RHCO(3)增加。两组的GFR、RBF以及钠、氯和钙的分数排泄均未改变。两组的重吸收磷酸盐均增加,完整组的磷酸盐分数清除率下降,TPTX组无显著变化。在TPTX犬中,在高钙血症基础上叠加PTE导致RHCO(3)降低(GFR从27.3降至23.9 mmol/升,P < 0.001),同时磷酸盐分数排泄增加,重吸收磷酸盐减少。在这组TPTX犬中,高钙血症使RBF从135.6降至105.8 ml/min,GFR无变化。输注PTE后RBF恢复至对照值。结论如下:(a)VE导致的RHCO(3)降低并非仅依赖于低钙对PTH的刺激;(b)PTE直接作用于肾小管使RHCO(3)降低;(c)Ca(++)增强RHCO(3),且此作用在无PTH和降钙素时发挥;(d)Ca(++)和PTH的作用似乎均非由血流动力学改变介导,尽管在输注Ca(++)的TPTX犬中不能排除这种可能性;(e)在无PTH时Ca(++)增强磷酸盐重吸收;这可能是高钙血症对磷酸盐重吸收的特异性作用或血清磷升高的非特异性结果。