Endogenous cardiotonic steroids and salt-sensitive hypertension

Abstract

Endogenous cardiotonic steroids (CTS), also called digitalis like factors, have been postulated to play important roles in pathogenesis of hypertension for nearly half of a century. For the past 50 years biomedical scientists have been in quest of an unidentified factor or hormone that both increases blood pressure and renal sodium excretion; this “natriuretic hormone” was, in fact, postulated to interact with the Na/K-ATPase. Recent discoveries have led to the identification of steroid molecules which are present in humans, rodents and amphibians, and which, in a complex manner, interact with each other and with the other systems that regulate renal salt handling and contribute to the salt-sensitivity of blood pressure. Recent findings include the specific identification of endogenous cardenolide (endogenous ouabain) and bufadienolide (marinobufagenin) CTS in humans along with the delineation of mechanisms by which CTS can signal through the Na/K-ATPase. Although CTS were first considered important in the regulation of renal sodium transport and arterial pressure, more recent work implicates these hormones in the central regulation of blood pressure and regulation of cell growth, and development of cardiovascular and renal fibrosis in particular.

Impairment of Na/K-ATPase Signaling in Renal Proximal Tubule Contributes to Dahl Salt-sensitive Hypertension

“…While volume expansion is considered to be the main cause of the salt-sensitive hypertension in the S rats (2,20), accumulating evidence, some from our laboratories, suggest that endogenous CTS regulate renal Na ϩ handling and BP through the Na/K-ATPase signaling (5,6,(21)(22)(23)(24)(25)(26). A role for endogenous CTS in salt sensitive hypertension has also been suggested by a number of authors (10,(27)(28)(29).…”

Ouabain Modulates the Distribution of Connexin 43 in Epithelial Cells

“…Following this scheme, ouabain has shown to influence a wide variety of physiological processes, including proliferation [16,17], growth [18], apoptosis [19][20][21] and cell mobility [22] in different tissues and organs. It also has been shown to influence the regulation of salt-sensitive blood pressure [23], salt handling in the kidney [24], vascular tone, Na + homeostasis [25] and embryonic kidney cell´s survival during malnutrition [26].…”

The Pressure of Aging

“…However, Na-pump ligands are not selective for renal NKA, but also inhibit N K A in the vasculature, leading to arterial constriction, and an increase in PVR and arterial blood pressure (Figure 3). 35,36,37,38,39 Interestingly, compared to normotensive control, older patients with resistant hypertension demonstrate greater blood pressure and PWV, higher plasma MBG (an NKA inhibitor), and decreased erythrocyte NKA activity. 40 In this regard, it is of note that the increase in arterial pressure induced by a chronic high NaCl intake (i.e.…”