Calcium and hypoxic injury in the renal medulla of the perfused rat kidney.
To study the interaction between calcium and the medullary hypoxic lesions found in isolated perfused rat kidneys, the acute effects of high extracellular calcium upon renal function and morphology were evaluated in kidneys perfused with cell-free medium at a total calcium concentration of 8 to 9 mg/dl (controls), 13 to 14 and 19 to 20 mg/dl (high Ca++). High Ca++ increased hypoxic damage to medullary thick ascending limbs from 58.2 +/- 4.0% of tubules in controls to 80.2 +/- 4.0% (P less than 0.005) in the deepest area of the outer medulla. Morphological changes in the cortex were minimal. The increase in damage to medullary thick limbs induced by high Ca++ was prevented by the calcium channel blocker verapamil. Addition of the calcium ionophore A23187 to controls reproduced the effects of high Ca++ with an increase in the proportion of damaged thick limbs to 92.1 +/- 4.1% (P less than 0.001 vs. controls). Addition of equimolar amounts of magnesium chloride did not reproduce the effect of high calcium perfusions. When transport activity was reduced with ouabain, high calcium perfusions were no longer associated with structural damage. In kidneys perfused with a medium enriched with amino acids, the proportion of tubules with severe, irreversible damage increased from 12 +/- 3 to 43 +/- 10% (P less than 0.01) after high calcium perfusion, and to 75 +/- 12% (P less than 0.001) after perfusion with the calcium ionophore. High extracellular and intracellular calcium appear to act in concert with hypoxia to increase the susceptibility of the renal medulla to injury by mechanisms potentially operative in hypercalcemic and ischemic nephropathy.(ABSTRACT TRUNCATED AT 250 WORDS)
Brezis
M
M
Department of Medicine, Hadassah University Hospital, Mount Scopus, Jerusalem, Israel.
Shina
A
A
Kidroni
G
G
Epstein
F H
FH
Rosen
S
S
D000596:Amino Acids / Q000494:pharmacology; D000818:Animals; D002135:Calcium-Binding Proteins / Q000633:toxicity; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006934:Hypercalcemia / Q000150:complications*; D000860:Hypoxia / Q000209:etiology* / Q000473:pathology; D007679:Kidney Medulla / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D008138:Loop of Henle / Q000187:drug effects / Q000473:pathology; D010477:Perfusion; D051381:Rats; D014700:Verapamil / Q000494:pharmacology
D000596:Amino Acids; D002135:Calcium-Binding Proteins; C025673:calciphorin; D014700:Verapamil