ABSTRACT
BACKGROUND: Numerous studies have demonstrated a strong relationship between circulating levels of marinobufagenin (MBG) and salt-sensitivity. Since salt-sensitive hypertensives have increased plasma levels of MBG and are known to be at a higher risk of having cardiovascular events, stroke and increased mortality, we evaluated the possibility of an association between MBG and ischemic stroke. In this pilot study, we determined plasma MBG levels in patients after surviving an ischemic stroke compared to similar age and gender groups of treated hypertensives and normotensive controls. METHODS: We measured plasma MBG levels in a total of 40 participants subdivided into three groups: After an ischemic stroke STR (n = 13), participants with a diagnosis of hypertension receiving blood pressure medication HT (n = 14) and normotensive control subjects CTL (n = 13). We used inferential statistics (parametric or non-parametric) and ordered logistic regression models (unadjusted and adjusted) and all statistical analyses were performed using Stata 14. RESULTS: We did not include a subject from the CTL group because of a diagnosis of glucose-6-phosphate dehydrogenase deficiency and an extreme plasma MBG value of 2,246 pmol/L. Participants' mean age was 60.4 ± 11.5 years; 56% were male. There was no significant difference between study groups (p > 0.05) for gender, age, and body mass index. HbA1c levels were significantly higher in the STR as compared to the CTL p < 0.05). In the STR group MBG levels were below the normal range (< 200 pmol/L) in three (23%), eight (61%) were in the normal range (200-400 pmol/L), while two (16%) had increased MBG values (> 400 pmol/L). Also, among the STR, the plasma MBG levels did not differ between those receiving and not receiving thrombolytic therapy (p > 0.05). From the 14 HT participants, six (43%) had MBG plasma levels within the normal range, and eight (57%) had high concentrations (> 400 pmol/L). Four (29%) of the treated hypertensives had extreme MBG levels (> 1,000 pmol/L) and normal values of blood pressure. CONCLUSION: There was no significant elevation of plasma MBG in survivors 24 h or more after an ischemic stroke. The extreme values of plasma MBG in 29% of the treated hypertensives suggests the presence of salt-sensitivity and a possible side effect of a specific combination of medications. Both of these findings contribute new knowledge to the design of studies to define if there is an MBG molecular mechanism underlying the complex associations among salt-sensitivity, hypertension, and ischemic stroke.
ABSTRACT
The Dahl salt-sensitive rat is a well-established model to study essential hypertension. We first described a subgroup of these rats based on the unique response pattern in systolic blood pressure during the first weeks of exposure to a high salt diet that included cataract formation. We classified this group as cataract-prone Dahl salt-sensitive rat. We also were able to predict and prevent cataract formation in these rats. Further studies showed an inhibition of lens Na, K-ATPase activity which may be in part responsible for the cataract formation. Other studies in Dahl salt-sensitive rats maintained on a high salt diet have also shown decreased Na, K-ATPase activity in several tissues and increased levels of endogenous circulating Na, K pump inhibitors. For over 20 years, endogenous cardiotonic steroids have been postulated to inhibit Na, K-ATPase in both humans as well as in experimental animal models of hypertension. Recent findings have shown results suggesting that there are several forms of cardiotonic steroids with minor differences in structural functionalities, site of production, and specific pump selectivity. We present original data that supports a role for cardiotonic steroids in disease progression related to increased salt-sensitivity. We found increased levels of free endogenous cardiotonic steroids in those rats that were classified as cataract-prone according to their initial systolic blood pressure response to a high salt intake when compared to non-cataract prone Dahl salt-sensitive rats and their control Dahl salt-resistant rats. The cataract-prone Dahl salt-sensitive rat is an animal model that can help and contribute to open a new door to possibly elucidate the role of endogenous cardiotonic steroids in the pathogenesis and progression of diseases related to salt-sensitive hypertension.
