Altered cations and muscle membrane ATPase activity in deoxycorticosterone acetate-salt spontaneously hypertensive rats.
The role of ions and cell membrane function in the pathogenesis of benign and malignant hypertension was investigated in spontaneously hypertensive rats (SHR). Ten-week-old male SHR (n = 50) and SHR treated with deoxycorticosterone acetate (DOCA; n = 70) and 1% NaCl drinking water were studied weekly for 14 weeks. Malignant hypertension developed only in DOCA-salt SHR and was characterised by severe hypertension, failure to thrive and renal fibrinoid necrosis. Fourteen DOCA-salt SHR and one SHR died. Extracellular (serum) and intracellular (erythrocyte and muscle) Na+, K+, Mg2+, Ca2+ and muscle membrane Na+,K(+)-adenosine triphosphatase (ATPase), Ca(2+)-ATPase and Mg(2+)-ATPase were measured at various stages in the development of malignant hypertension. Three developmental phases were defined: benign, premalignant and malignant. DOCA-salt SHR showed persistent hypokalaemia. In the benign phase, there were no differences in Na+, Mg2+ and Ca2+ between SHR and DOCA-salt SHR. In the premalignant phase, serum and erythrocyte Mg2+ and ATPase activity were significantly lower in DOCA-salt SHR compared with SHR. During the late premalignant and malignant phases, intracellular Ca2+ and Na+ were significantly higher in the DOCA-salt SHR compared with SHR. In view of these findings, the abnormalities in DOCA-salt SHR during the early phases of blood pressure elevation could be contributory factors to the development of malignant hypertension.
Touyz
R M
RM
Department of Medicine, University of the Witwatersrand Medical School, Johannesburg, South Africa.
Marshall
P R
PR
Milne
F J
FJ
D000251:Adenosine Triphosphatases / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002412:Cations / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D003900:Desoxycorticosterone; D004912:Erythrocytes / Q000378:metabolism; D006973:Hypertension / Q000139:chemically induced / Q000201:enzymology* / Q000473:pathology; D007678:Kidney Glomerulus / Q000473:pathology; D008274:Magnesium / Q000378:metabolism; D008297:Male; D009132:Muscles / Q000201:enzymology*; D009336:Necrosis; D011188:Potassium / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D012964:Sodium / Q000378:metabolism; D012965:Sodium Chloride
D002412:Cations; D003900:Desoxycorticosterone; D012965:Sodium Chloride; D012964:Sodium; D000251:Adenosine Triphosphatases; D008274:Magnesium; D011188:Potassium; D002118:Calcium