title: Endogenous inhibitors of the Na+, K(+)-pump and platelet Ca2+ handling in hypertension.
abstract: Inhibition of the Na(+)-K+ pump by digitalis compounds has been reported to increase intracellular Na+ and Ca2+ concentrations and to stimulate Na(+)-H+ exchange. The activity of endogenous digitalis-like compounds, proposed to promote natriuresis and to raise blood pressure, has been found to be increased in volume expansion and hypertension. The enhanced cytosolic [Ca2+] present in platelets from hypertensive patients may thus originate from inhibition of the Na(+)-K+ pump by endogenous inhibitors, enhanced mobilization of internal Ca2+ stores due to phospholipase C activation and/or structural membrane defects. In unstimulated platelets from essential hypertensives, the increase in [Ca2+]i depends on external Ca2+, thereby underlining the importance of Ca2+ influx. The observation that [Ca2+]i was also enhanced in erythrocytes (p = 0.03) demonstrates that intracellular stores are not required for this rise. Plasma digitalis-like activity was positively correlated with platelet [Ca2+]i (inhibition of renal Na+,K(+)-ATPase, competition with ouabain binding, p less than 0.01). Platelet [Ca2+]i also rose during chronic digoxin administration (p less than 0.02) but not after acute in vitro ouabain treatment. The alkalinisation of platelet cytosol (p = 0.005) also agrees with the stimulation of the Na(+)-H(+)-exchange. In conclusion, these results are compatible with a participation of endogenous Na(+)-K+ pump inhibitors in the control of cytoplasmic [Ca2+] and cell excitability.
authors.affiliation: Department of Pharmacology, INSERM U7, CHU Necker, Paris, France.
authors.forename: M A
authors.initials: MA
authors.lastname: Devynck
authors.forename: M
authors.initials: M
authors.lastname: David-Dufilho
authors.forename: C
authors.initials: C
authors.lastname: Astarie
authors.forename: M
authors.initials: M
authors.lastname: Mazeaud
authors.forename: M G
authors.initials: MG
authors.lastname: Pernollet
authors.forename: K H
authors.initials: KH
authors.lastname: Le Quan Sang
mesh_terms: D000328:Adult; D001792:Blood Platelets / Q000378:metabolism*; D001798:Blood Proteins / Q000378:metabolism*; D002118:Calcium / Q000097:blood*; D002298:Cardenolides; D004077:Digoxin; D005260:Female; D006801:Humans; D006973:Hypertension / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011188:Potassium / Q000097:blood / Q000378:metabolism; D012503:Saponins; D012701:Serotonin / Q000097:blood; D012964:Sodium / Q000097:blood / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors*
chemical_list: D001798:Blood Proteins; D002298:Cardenolides; D012503:Saponins; C034504:digoxin-like factors; D012701:Serotonin; D004077:Digoxin; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase; D011188:Potassium; D002118:Calcium