Marinobufagenin may mediate the impact of salty diets on left ventricular hypertrophy by disrupting the protective function of coronary microvascular endothelium

Individuals who eat salty diets and who are “salt-sensitive” tend to have increased left ventricular mass, independent of blood pressure; this phenomenon awaits an explanation. It is clear that local up-regulation of angiotensin II (AngII) production and activity play a key role in the induction of left ventricular hypertrophy (LVH). Recent evidence suggests that a healthy coronary microvascular endothelium opposes this effect by serving as a paracrine source of nitric oxide (NO), a natural antagonist of AngII activity, and that up-regulation of this mechanism can account for the protective role of bradykinin with respect to LVH. The coronary microvasculature also possesses NAD(P)H oxidase activity that can generate superoxide, inimical to the bioactivity of endothelial NO. There is now good reason to believe that the triterpenoid marinobufagenin (MBG), a selective inhibitor of the α-1 isoform of the sodium pump, mediates the impact of salty diets on blood pressure; production of MBG by the adrenal cortex is boosted when salt-sensitive animals are fed salty diets. It is hypothesized that coronary microvascular endothelium expresses the α-1 isoform of the sodium pump, and that MBG thus can target this endothelium. If that is the case, MBG would be expected to decrease membrane potential in these cells; as a consequence, superoxide production would be up-regulated, NO synthase activity would be down-regulated, and myocardial NO bioactivity would thus be suppressed. This would offer a satisfying explanation for the impact of salt and salt-sensitivity on risk for LVH. If expression of the α-1 isoform of the sodium pump is a more general property of vascular endothelium, MBG may suppress NO bioactivity in other regions of the vascular tree, thereby contributing to other adverse effects elicited by salty diets: reduced arterial compliance, medial hypertrophy, impaired endothelium-dependent vasodilation, hypertensive/diabetic glomerulopathy, increased risk for stroke, and hypertension.