Evidence for a parathyroid hormone-dependent influence of calcium on the glomerular ultrafiltration coefficient.

Humes, H. David; Ichikawa, Iekuni; Troy, JL; Bm, Brenner

doi:10.1172/jci108922

Cited by 66 publications

(16 citation statements)

References 24 publications

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“…The fact that acute and chronic hypercalcemia cause a decreased RBF and GFR in both man and experimental animals has been repeatedly reported (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15) (35)(36)(37)(38).…”

Section: Discussionmentioning

confidence: 94%

“…It is attractive to postulate that this dissociation points to an effect on the ultrafiltration coefficient as was shown in the acute setting (13). It is thus possible that in hypercalcemia AII-mediated contraction of glomerular mesangial cells is accentuated (39), an effect that is even more marked when glomerular PG synthesis (40,41) is inhibited.…”

Section: Discussionmentioning

confidence: 96%

“…The association of acute and chronic hypercalcemia with decrements in renal blood flow (RBF)' and glomerular filtration rate (GFR) has been widely recognized in both man and experimental animals (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15). While the mechanisms responsible for the decrement in RBF and GFR have been studied in anesthetized, acutely hypercalcemic animals, there have been no such studies in the setting of chronic hypercalcemia.…”

mentioning

confidence: 99%

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Control of Renal Hemodynamics and Glomerular Filtration Rate in Chronic Hypercalcemia

Levi¹,

Ellis²,

Berl³

1983

J. Clin. Invest.

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A B S T R A C T The role of prostaglandins (PG), reninangiotensin system (RAS) and calcium (Ca) in the control of renal hemodynamics and glomerular filtration rate (GFR) in chronic hypercalcemia (serum Ca 12.8 mg%) was studied. Renal blood flow (RBF, 6.39 ml/ min per gram kidney weight [gkw]) and GFR (0.52 ml/min per gkw) were significantly decreased in hypercalcemic rats when compared with normocalcemic rats (7.15, P < 0.001 and 0.74, P < 0.05, respectively). These changes in RBF and GFR occurred independent of any significant alterations in systemic hemodynamics, blood and plasma volume. Inhibition of the renal PG with indomethacin resulted in marked decrements in both RBF (6.39-4.12 ml/min per gkw, P < 0.01) and GFR (0.52-0.19 ml/min per gkw, P < 0.01) in hypercalcemic rats, whereas there was no significant alterations in normocalcemic rats. Inhibition of the RAS with captopril resulted in marked increments in both RBF (6.39-7.35 ml/min per gkw, P < 0.05) and GFR (0.52-0.74 ml/min per gkw, P < 0.05) in hypercalcemic rats. In fact, there was no significant difference from the RBF and GFR of similarly treated normocalcemic rats. Similar results were also obtained with the competitive angiotensin II (AII) antagonist (sarcosyll-isoleucyl5-glycyl8) AII. Since both the renal PG and the RAS are involved in the control of RBF and GFR in hypercalcemia, the role of each is best revealed in the absence of the other. Hence, comparison of the RBF and GFR in the PG-inhibited hypercalcemic rats in the presence of AII (4.12 and 0.19 ml/ min per gkw, respectively) and absence of AII (5.99 and 0.53 ml/min per gkw, P < 0.01 for both) reveals the vasoconstrictive role for All in hypercalcemia. On the other hand, comparison of the RBF and GFR in the AII-inhibited hypercalcemic rats in the presence of PG (7.35 and 0.74 ml/min per gkw, respectively) and absence of PG (5.99 and 0.53 ml/min per gkw, P < 0.01 and P < 0.05, respectively) reveals the vasodilatory role for PG in hypercalcemia. Finally, comparison of the RBF and GFR in both PG-and Allinhibited hypercalcemic rats (5.99 and 0.53 ml/min per gkw, respectively) with similarly treated normocalcemic rats (7.30 and 0.94 ml/min per gkw, P < 0.001 and P < 0.005, respectively) reveals the vasoconstrictive role for Ca in chronic hypercalcemia. Our study therefore demonstrates that in chronic hypercalcemia the RBF and GFR are controlled by an active interplay of the vasoconstrictive effect of AII, the vasodilatory effect of renal PG, and the direct vasoconstrictive effect of Ca, independent of either AII or PG. The sum total of these forces produces a modest but significant decrease in RBF and GFR. INTRODUCTIONThe association of acute and chronic hypercalcemia with decrements in renal blood flow (RBF)' and glomerular filtration rate (GFR) has been widely recognized in both man and experimental animals (1-15). While the mechanisms responsible for the decrement in RBF and GFR have been studied in anesthetized, acutely hypercalcemic animals, there have been no such studies in the setting...

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Section: Discussionmentioning

confidence: 94%

Section: Discussionmentioning

confidence: 96%

mentioning

confidence: 99%

See 1 more Smart Citation

Control of Renal Hemodynamics and Glomerular Filtration Rate in Chronic Hypercalcemia

Levi¹,

Ellis²,

Berl³

1983

J. Clin. Invest.

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“…At the end of the 20 min preincubation period, 50 i±l of 5 mM 1-methyl-3-isobutyl xanthine (MIX) dissolved in KRB and either 100 ,Ll of KRB (controls), or hormones and drugs dissolved in 100 ,Iu KRB were added to the various suspensions. These additions were made within a time interval of 6 s. The final volume of each suspension then was 500 ul of KRB (with 0.5 mM MIX) and the final concentration of various test agents as indicated in Results.…”

Section: Methodsmentioning

confidence: 99%

Modulation of Cyclic Nucleotides in Isolated Rat Glomeruli

et al. 1978

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A B S T R A C T Because glomerular functions are modulated by numerous humoral agents, probably acting through cyclic nucleotides, the effects of some polypeptide hormones and biogenic amines on cyclic AMP (cAMP) and cyclic 3',5'-guanosine monophosphate (cGMP) were studied in glomeruli isolated from rat renal cortex. Glomeruli and cortical tubules were prepared by a combination of sieving and density-gradient centrifugation. Under basal conditions, the contents of cAMP and cGMP in glomeruli were significantly higher than in tubules and unfractionated renal cortical tissue.Histamine caused a striking increase in cAMP in glomeruli (+A% 675±87) and, to a lesser degree, increased cAMP in tubules (+A% 103+25) or in tissue slices. This stimulation was dose-dependent in the range of 1 ,uM-1 mM histamine. Metiamide (an H2-antagonist), but not pyrilamine (an H,-antagonist) blocked the effect of histamine on cAMP, which indicates that histamine causes its effect via interaction with H2 receptors. Histamine caused less extensive increases in cGMP in both glomeruli and tubules. Carbamylcholine caused a marked increase in cGMP in glomeruli (+A 295±7) and a much lower increase in tubules (+A% 70+20); these effects were blocked by 1334atropine. Parathyroid hormone (1 ug/ml) increased cAMP and, to a much lesser degree, also cGMP in glomeruli. In tubules, parathyroid hormone caused nmuch more extensive increases in cAMP than in glomeruli; no changes, or rather a small decline in cGMP, was observed. Angiotensin-I1 (2 uM) markedly lowered cAMP in glomeruli (-A% -45±8) and in tubules (-A% 33±7) but had no effect on cGMP. Bradykinin (20 ,M) did not consistently influience either cAMP or cGMP in glomeruli or tubules.Present results demonstrate that cAMP and cGMP metabolism in glomeruli are controlled independently by humoral agents known to alter glomerular functions in vivo. Our findings are consistent with the view that histamine and cholinergic agents generated and (or) released locally in glomeruli or in their vicinity may play important roles as mediators of immunopathological injury of glomeruli, and that these effects are mediatecl by cAMP and (or) cGMP through interaction with H2 receptors and muscarinic receptors. Likewise, our results suggest that the effects of angiotensin-II and parathyroid hormone on glomerular dynamics may be mediated by cyclic nucleotides.Thus, we surmise that extrarenal as well as intrarenal humoral agents may play an important role in the pathology and physiology of glomeruli through mediation of either cAMP, cGMP, or both. INTRODUCTIONIt has become increasingly evident in recent years that many extrarenal and intrarenal humoral agents mraymodulate diverse aspects of glomerular function (1). For example, the administration of agents such as para- thyroid hormone (PTH)' (2), angiotensin (3, 4), bradykinin, acetylcholine (5,6), and others (1) causes changes in glomerular microcirculation, hydraulic permeability, or in the ultrafiltration properties of glomerular membrane. Perhaps more importantly,...

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“…First, the development of hypercalcemia directly decreases the GFR, reducing the amount of calcium filtered (50). Second, hypercalcemia activates the CaSR in the TALH and medullary collecting duct.…”

Section: Pathogenesis Of the Milk Alkali Syndromementioning

confidence: 99%