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(Hypertension. 1995;26:781.)
© 1995 American Heart Association, Inc.

Articles

Endogenous Marinobufagenin-like Immunoreactive Factor and Na⁺,K⁺ ATPase Inhibition During Voluntary Hypoventilation

Presented in part at the XV European Section Meeting of the International Society for Heart Research, Copenhagen, Denmark, June 8-11, 1994.

Alexei Y. Bagrov; Olga V. Fedorova; Joy L. Austin-Lane; Renata I. Dmitrieva; David E. Anderson

From the Laboratory of Behavioral Sciences (A.Y.B., O.V.F., J.L.A.-L., D.E.A.), National Institute on Aging, 4940 Eastern Ave, Baltimore, Md, and the Laboratory of Pharmacology (A.Y.B., O.V.F., R.I.D.), Sechenov Institute of Evolutionary Physiology and Biochemistry, St Petersburg, Russia.

Correspondence to Dr Alexei Y. Bagrov, Laboratory of Behavioral Sciences, National Institute on Aging, 4940 Eastern Ave, Baltimore, MD 21224.

Abstract In previous studies investigators found that conditioned hypoventilatory breathing potentiated a sodium-sensitive form of hypertension in dogs that was not mediated by sympathetic nervous system arousal. Our study investigated effects of 30 minutes of voluntary hypoventilation, maintained by a respiratory gas monitor and feedback procedure, in 16 normotensive humans of both sexes on (1) plasma concentrations of endogenous digitalis-like factors (ouabain-like and marinobufagenin-like immunoreactivity), (2) activity of erythrocyte Na⁺,K⁺-ATPase, (3) inhibitory activity of plasma Na⁺,K⁺-ATPase, and (4) blood pressure. Increased end tidal PCO₂ (41±0.78 mm Hg versus 37.6±1.03 mm Hg) was associated with (1) an increase in plasma marinobufagenin-like immunoreactivity (1.23±0.47 versus 4.96±1.19 nmol/L), (2) an inhibition of Na⁺,K⁺-ATPase in red blood cells (3.68±0.22 versus 2.15±0.25 mmol P_i · mL^-1 · h^-1; P<.01), (3) increase in plasma Na⁺,K⁺-ATPase inhibitory activity (34.9±4.0% versus 48.8±2.1%, P<.02), and (4) increases in systolic (112.4±2.6 versus 107.6±1.8 mm Hg) and diastolic (73.5±2.1 versus 68.8±2.1 mm Hg) blood pressures. Plasma levels of ouabain-like immunoreactivity did not increase significantly. Incubation of erythrocytes obtained during hypoventilation with antidigoxin antibody restored the Na⁺,K⁺-ATPase activity (3.99±0.34 mmol P_i · mL^-1 · h^-1). Cessation of hypoventilation was associated with decreases in diastolic blood pressure (70.5±2.2 mm Hg) and restoration of Na⁺,K⁺-ATPase activity in erythrocytes (2.99±0.43 mmol P_i · mL^-1 · h^-1). On the basis of organic extraction and thin-layer chromatography followed by separation with the use of reverse-phase high-performance liquid chromatography, the material coeluting with marinobufagenin was separated from human urine. This material cross-reacted with anti-marinobufagenin antibody. These results demonstrate the presence of a bufadienolide-like Na⁺,K⁺-ATPase inhibitor in human plasma and support the view that breathing pattern may participate in blood pressure control via release of a rapidly acting circulating Na⁺,K⁺-ATPase inhibitor.

Key Words: hypoventilation • Na⁺,K⁺-exchanging ATPase • bufanolides • hypertension

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