Different cation transport inhibitor in benign and malignant experimental renal hypertension.
The role of circulating humoral agents in the pathogenesis of abnormal vascular wall cation composition in benign and malignant renal hypertension was investigated. Male F344 rats with chronic benign (n = 38) and malignant (n = 44) one-kidney, one clip (1K1C) hypertension and normotensive control rats (n = 63) were studied. Malignant hypertension developed spontaneously and was characterized by failure to thrive, weight loss, oedema, renal insufficiency, anaemia or haemoconcentration and hyperkalaemia. For bio-assay, monolayers of quiescent vascular smooth muscle cells from F344 rats were incubated in plasma or plasma extracts of normotensive and hypertensive rats for measurement of labelled rubidium (86Rb) uptake in the presence and absence of 2 mmol/l ouabain and/or 1 mmol/l furosemide. Compared with controls, ouabain-sensitive Rb uptake of cells was reduced in plasma extracts but not in whole plasma of rats with benign hypertension. Ouabain-sensitive Rb uptake was unchanged and ouabain-insensitive Rb uptake was reduced in both plasma and plasma extracts of rats with malignant hypertension. The latter was due to a reduction in furosemide-sensitive Rb uptake. In malignant hypertension, the increased sodium (Na) content of the aorta which characterizes benign hypertension was reversed and bladder wall Na content was reduced. The findings suggest that in malignant hypertension a circulating, furosemide-like inhibitor of ouabain-insensitive cation transport is the cause of vascular wall Na depletion and of diuresis and natriuresis that trigger the syndrome.
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002412:Cations / Q000378:metabolism*; D003864:Depression, Chemical; D004195:Disease Models, Animal; D005665:Furosemide / Q000494:pharmacology; D006977:Hypertension, Renal / Q000378:metabolism*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D010042:Ouabain / Q000494:pharmacology; D011868:Radioisotopes; D051381:Rats; D011916:Rats, Inbred F344; D012413:Rubidium
D002412:Cations; D011868:Radioisotopes; D010042:Ouabain; D005665:Furosemide; D012413:Rubidium