Endogenous digitalislike circulating substances in spontaneously hypertensive rats.
Circulating digitalislike compounds have been proposed to be involved in some Na+-dependent types of experimental hypertension and in human essential hypertension. The level of circulating Na+-K+ pump inhibitor(s) was investigated in the spontaneously hypertensive rat of the Okamoto strain (SHR), its normotensive control, Wistar-Kyoto rat (WKY), and the regular Wistar rat using the following criteria: the ability of whole plasma to inhibit the total active Na+ efflux from Wistar rat erythrocytes and to cross-react with digoxin antibodies and the ability of plasma extracts to inhibit Na+,K+-adenosine triphosphatase (ATPase) activity of membranes from rat kidney. SHR plasma inhibited the net Na+ efflux from Wistar erythrocytes by up to 27% compared with WKY or Wistar plasma. For a given number of cells, the inhibition increased with the amount of available plasma. Cross-reactivity with digoxin antibodies was twice as high in SHR as in WKY or Wistar plasma. It was already enhanced in 3- to 4-week-old rats. Plasma extracts from SHR significantly inhibited Na+,K+-ATPase activity when compared with WKY extracts (75.6 +/- 2.6 vs 89.3 +/- 2.4 mumol Pi/mg/hr; p less than 0.01) but did not differ from Wistar plasma extracts. These results strongly suggest that circulating digitalislike compound(s) are present in elevated amounts in SHR as early as 3 to 4 weeks of age, but their exact participation in blood pressure elevation or maintenance remains to be clarified.
Wauquier
I
I
Department of Pharmacology, INSERM U7, Paris, France.
Pernollet
M G
MG
Grichois
M L
ML
Lacour
B
B
Meyer
P
P
Devynck
M A
MA
D000818:Animals; D001794:Blood Pressure; D001798:Blood Proteins / Q000378:metabolism*; D002298:Cardenolides; D003429:Cross Reactions; D004077:Digoxin; D004912:Erythrocytes / Q000378:metabolism; D006973:Hypertension / Q000235:genetics / Q000378:metabolism*; D007473:Ion Channels / Q000378:metabolism*; D008297:Male; D011863:Radioimmunoassay; D051381:Rats; D011918:Rats, Inbred SHR; D011919:Rats, Inbred Strains; D011921:Rats, Inbred WKY; D012503:Saponins; D012964:Sodium / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors*
D001798:Blood Proteins; D002298:Cardenolides; D007473:Ion Channels; D012503:Saponins; C034504:digoxin-like factors; D004077:Digoxin; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase