K+ channel blockers: natriuretic potency correlates to vascular ATP-sensitive K+ channel blockade.

Using analogs of known vascular ATP-sensitive K+ channel (KATP) blockers, we identified compounds with a wide range of potencies (over 500-fold) in their capacity to block the hypotensive response of 0.2 mg/kg pinacidil in rats. The most potent of these, U-97025E, belongs to a newly disclosed class of compounds, the cyanoguanidines.

Observations on the nature, biosynthesis, secretion and significance of endogenous ouabain.

The human circulation contains four readily distinguishable biologically active inhibitors of the sodium pump that appear to be endogenous to mammals. Of these, one has been purified to homogeneity and by numerous chromatographic, mass spectral, biochemical, and physiological analyses has been shown to be a novel steroidal isomer of ouabain in which the location and orientation of two or more steroidal hydroxyl groups differ. The human endogenous "ouabain" (EO) is a high affinity reversible inhibitor of the pump with inotropic and vasopressor activity.

K-ATP-blocking diuretic PNU-37883A reduces plasma renin activity in dogs.

We determined the effects of the K-adenosine triphosphate (ATP)-blocking diuretic PNU-37883A on plasma renin activity (PRA) in conscious and anesthetized dogs. In conscious dogs, oral PNU-37883A (6-60 mg/kg) was less potent than hydrochlorothiazide (0.15-1.

The natriuretic activity of the K+ channel blocker U-37883A displays an ADH-dependence.

We reported previously that K+ channel blockers induce diuresis and natriuresis in conscious and anesthetized rats. Free-water clearance studies suggested that K+ channel blockers inhibit NaCl reabsorption in the thick ascending limb (TAL) by blocking K+ recycling through a low-conductance, usually open, apical ATP-sensitive K+ channel. In the present study, we measured the effect of U-37883A (15 mg/kg, i.