Christine G. Schnackenberg

Loop and thiazide diuretics are common therapeutic agents for the treatment of sodium retention and oedema. However, resistance to diuretics and decreases in renal function can develop during diuretic therapy. Adenosine causes renal vasoconstriction, sodium reabsorption, and participates in the tubuloglomerular feedback mechanism for the regulation of glomerular filtration rate. We tested the hypothesis that the selective adenosine A₁ receptor antagonist FK838 is orally active and causes diuresis and natriuresis, but maintains glomerular filtration rate in normal rats or in rats with furosemide resistance. In normal male Sprague – Dawley rats, FK838 dose‐dependently increased urine flow and sodium and chloride excretion while sparing potassium. In combination with furosemide, FK838 enhanced the diuretic and natriuretic actions of furosemide to the same extent as hydrochlorothiazide and did not increase the potassium loss in normal rats. In furosemide‐resistant rats, FK838 increased urine flow and electrolyte excretion to a greater extent than hydrochlorothiazide. In addition, hydrochlorothiazide significantly decreased glomerular filtration rate, whereas FK838 maintained glomerular filtration rate in furosemide‐resistant rats. This study shows that the adenosine A₁ receptor antagonist FK838 is orally active and causes potent diuresis and natriuresis and maintains glomerular filtration rate in normal or furosemide‐resistant rats. Adenosine A₁ receptor antagonists may be novel therapeutics for the treatment of oedema in normal or otherwise diuretic‐resistant patients. British Journal of Pharmacology (2003) 139, 1383–1388. doi:10.1038/sj.bjp.0705370

The renal microvasculature is an important component in the regulation of kidney function. Recent studies suggest that oxygen radicals can contribute to the modulation of renal cortical and medullary microvascular function under normal conditions as well as in pathophysiological conditions such as diabetes mellitus and hypertension. This review focuses on studies that indicate oxygen radicals can cause renal vasoconstriction, mediate the vasoconstriction of other agonists, and modulate nitric oxide-dependent actions in the normal kidney. Hypertension and diabetes mellitus are associated with oxidative stress. Recent investigations suggest that oxygen radicals may contribute to the enhanced renal vascular tone, increased sensitivity to vasoconstrictors, impaired endothelium-dependent vasodilation, and enhanced tubuloglomerular feedback found in these pathophysiological conditions.