There are numerous reports in the literature about elevated level of a sodium transport inhibitory factor (STIF) in various models of hypertension. The exact chemical nature of this factor(s) is not yet clarified, but its crossreactivity with antidigitalis antibodies has been established. It is a logical assumption that sensitivity to a putative STIF can mofidy the pathogenesis of hypertension. A decreased sensitivity might limit the hypertensive potency of a putative STIF. An increased sensitivity, however, might result in a more severe hypertension when an elevated level of the factor is present in the circulation or may lead to hypertension at an even normal STIF concentration. Our project will investigate this hypothesis. Since the naturally occurring STIF is not available in a pure form at the present time, we will try to imitate its action on the active sodium pump by using cardiac glycosides. These chemicals are specific and potent inhibitors of the sodium pump. We will chronically administer digoxin to two hypertensive rat models: the Dahl Salt Sensitive and the Spontaneously Hypertensive strains, and measure their blood pressure as an index of their sensitivity to sodium pump inhibition. The cellular effects of the chronic digoxin administration will be characterized by measuring ouabain binding, 86Rb+ uptake and intracellular Na+, K+ concentrations of the red blood cells (RBC). In vitro effects of ouabain exposure in the growing medium on the same parameters of rat vascular smooth muscle cells (VSMC's) will also be measured. The changes in the Na+ K+ homeostasis of RBC and VSMC will be related to the blood pressure resulting from chronic digitalis administration. Our main purpose in this project is to delineate blood pressure responses and differences in Na+ K+ homeostasis among hypertensive and normotensive rat strains, when challenged by chronic digitalis treatment. In addition to the well established salt sensitivity in hypertension, we intend to demonstrate a correlation between digitalis sensitivity and hypertension. We believe that the hypertensive animal models included in this study will facilitate the classification of a large pool of patients with essential hypertension.
