Increases in Plasma Ouabainlike Immunoreactivity during Surgical Extirpation of Pheochromocytoma.

Abstract

The ouabainlike factor (OLF) is thought to be an important modulator of salt and water metabolism. Plasma OLF could be derived from the central nervous system and/or the adrenal gland. Since the adrenal medulla is of neural origin, the cytology of pheochromocytoma of adrenomedullary origin resembles that of neuronal cells. Ouabainlike immunoreactivity (OLI) is, in fact, present in the adrenal medulla as shown by immunohistochemistry.The plasma levels of catecholamines and OLI were significantly elevated during surgical extirpation of pheochromocytoma in this case. To clarify the origin of circulating OLI in a patient with pheochromocytoma, the relationship between plasma OLI and catecholamines during adrenalectomy was investigated. Plasma catecholamine levels exceeded the normal reference interval, and plasma OLI was positively correlated with the patient's plasma level of norepinephrine.The peak level during operation was about 10 times higher than the baseline level. Both levels reached a maximum when the tumor was mechanically pressed, and then gradually decreased thereafter.The level of OLI in the tumor was higher than that of the normal adrenal cortex. When OLI in the tumor was characterized by reversed-phase high-performance liquid chromatography, the retention time of OLI corresponded with that of authentic ouabain. These results suggest that the circulating OLI in this patients was derived mainly from the pheochromocytoma of adrenomedullary origin. (Hypertens Res 1999; 22: 135-139)

Endogenous Cardiotonic Steroids: Physiology, Pharmacology, and Novel Therapeutic Targets

“…These researchers purified a substance from the PC12 pheochromocytoma cell line that originated from progesterone and that, by its chromatographic and mass spectrometric properties, was not different from authentic ouabain (Komiyama et al, 2001). The above findings agree with a clinical observation of a marked reduction in the levels of circulating EO in a patient after the surgical removal of a pheochromocytoma (Komiyama et al, 1999). …”

A novel endogenous digitalis, telocinobufagin, exhibits elevated plasma levels in patients with terminal renal failure

“…Therefore, inhibitors of this system have been thought to be deeply involved in the pathogenesis of a certain sort of hypertension [32]. The endogenous Na + , K + -ATPase inhibitor, ouabain, or its closely related compounds have been identified as present in nanomolar concentrations in the plasma and several tissues, and we observed a change in ouabain-like immunoreactivity in certain pathophysiological conditions [13,20,33]. Recently, we identified ouabain and digoxin as structurally confirmed substances in human plasma by liquid chromatography/mass spectrometry.…”

The central mechanism underlying hypertension: a review of the roles of sodium ions, epithelial sodium channels, the renin–angiotensin–aldosterone system, oxidative stress and endogenous digitalis in the brain

“…As noted, OLI is also detected in the rat adrenal medulla by immunohistochemistry. 99 To summarize, ouabain and digoxin are produced by neuronal cells in the hypothalamus and by adreno-cortical and -medullary cells.…”