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Chronic lead exposure may cause hypertension in normotensive rats. This hypertensinogenic effect has been attributed to perturbations in the renin-angiotensin axis, the contractile resporase of the vascular smooth muscle, or the intracellular Ca2+ homeostasis as a consequence of the inhibition of Na+-K+-ATPase activity. In this study we examined the short-term effect of lead exposure on blood pressure, plasma renin activity, vascular contractility, and renal Na+-K+-ATPase activity and abundance in the spontaneously hypertensive rat. Our data indicate that modest lead exposure caused blood pressure elevation within two weeks in this rat strain that is genetically susceptible to the development of hypertension. This rapid blood pressure-elevating effect did not appear to depend on the mechanisms described in hypertension associated with more chronic lead exposure listed above. This acute model provides an additional approach to the study of lead-induced hypertension.

Background Patients treated with adrenal steroids for chronic obstructive lung disease have elevated skeletal muscle ouabain binding sites. We have recently shown that rats treated for 14 days with the synthetic glucocorticoid dexamethasone (dex) have 50% increases in Na,K-ATPase (NKA) α2 and β1 isoform protein levels, the major isoform in muscle. These findings raise the concern that in this group acute stimulation of an increased pool of muscle NKA by catecholamines or insulin could precipitate acute hypokalemia. Aim determine if the dex induced increase in muscle sodium pumps provokes an increase in insulin stimulated cellular K+ uptake. Alternatively, dex treatment could provoke insulin resistance of cellular K+ uptake analogous to dex induced insulin resistance of glucose uptake. Method Rats were treated with dex (0.1 mg/kg/day) or vehicle via subcutaneous osmotic mini-pumps for 7 days (n=6 each). Vehicle infused rats were paired by weight to dex infused rats since dex treatment slowed weight gain. In conscious rats with tail venous and arterial cannulas, insulin (5 mU/kg.min) stimulated cellular uptake of K+ and glucose were measured by determining the amount of exogenous K+ infusion (Kinf) and glucose infusion (Ginf) needed to clamp plasma K+ and glucose at their baseline levels, measured at 10 min intervals over 2.5 hrs. Results In the dex treated group insulin stimulated cellular uptake of glucose was reduced, as expected (Ginf (mmol/kg/hr): 10.2 ± 0.6 in shams, 5.2 ± 0.6 in dex treated). Insulin stimulated cellular uptake of K+ was, likewise, reduced (Kinf (μmol/kg/hr): 533 ± 77 in shams, 266 ± 82 in dex treated). NKA α2 levels in dex treated group, measured by immunoblots, were increased 1.67 ± 0.03 fold in gastrocnemius and 1.35 ± 0.1 in soleus; NKA α1 levels were unchanged. Conclusion These results demonstrate that although dexamethasone treatment significantly increases muscle Na K ATPase levels, insulin stimulated cellular K+ uptake is significantly depressed, novel evidence for insulin resistance of K+ clearance during chronic dexamethasone treatment. DK057678.