Relationships among endogenous digitalis-like factors in essential hypertension.
Elements of a hypothesis that relate endogenous digitalis-like factors to both natriuretic hormone and hypertension are briefly reviewed. The stimulus for secretion of these factors appears to involve a tendency toward a state of extracellular fluid volume expansion as a consequence of an inherited or an acquired defect in renal function. Several studies implicate the brain and, in particular, the hypothalamus in the control of the secretion. The digitalis-like factors are thought to act by partial inhibition of active sodium transport, thereby promoting increased intracellular levels of Na+ and Ca2+ in a variety of cell types. In the kidney, inhibition of sodium transport leads to a compensatory natriuresis to correct the tendency for volume overload. In smooth muscle, the inhibition of sodium transport will indirectly increase intracellular calcium levels. The increased availability of Ca2+ will elevate muscle tone and increase peripheral vascular resistance. Also presented are criteria that may be used to characterize digitalis-like activity in samples and extracts obtained from purification procedures. Finally, we review our measurements of the 6-h integrated plasma levels of digitalis-like factors and other hormones for normotensive subjects and patients with essential hypertension. The data indicate the presence of two classes of digitalis-like factors with potentially different roles in electrolyte metabolism and hypertension.
Hamlyn
J M
JM
Levinson
P D
PD
Ringel
R
R
Levin
P A
PA
Hamilton
B P
BP
Blaustein
M P
MP
Kowarski
A A
AA
D000450:Aldosterone / Q000097:blood; D000818:Animals; D001798:Blood Proteins / Q000032:analysis / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D002298:Cardenolides; D004077:Digoxin; D004837:Epinephrine / Q000097:blood; D006801:Humans; D006973:Hypertension / Q000235:genetics / Q000503:physiopathology*; D045283:Natriuretic Agents; D009638:Norepinephrine / Q000097:blood; D011506:Proteins / Q000494:pharmacology; D011863:Radioimmunoassay; D012083:Renin / Q000097:blood; D012503:Saponins; D012964:Sodium / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors; D014655:Vascular Resistance
D001798:Blood Proteins; D002298:Cardenolides; D045283:Natriuretic Agents; D011506:Proteins; D012503:Saponins; C034504:digoxin-like factors; D000450:Aldosterone; D004077:Digoxin; D012964:Sodium; D012083:Renin; D000254:Sodium-Potassium-Exchanging ATPase; D002118:Calcium; D009638:Norepinephrine; D004837:Epinephrine