Objectives: This study defined the modulating actions of sulfonylurea on acute release of atrial natriuretic peptide (ANP) in experimental acute heart failure. Background: Sulfonylurea drugs, blockers of cardioprotective ATP- sensitive K+ (K(ATP)) channels, may increase the risk of early cardiovascular mortality. In cardiovascular diseases such as acute heart failure, early release of ANP is essential for cardiorenal homeostasis. Although K(ATP) channels regulate secretion of hormones, such as insulin, it is unknown whether sulfonylureas interfere with ANP release in acute heart failure. Methods: The effects of acute administration of glyburide (0.3 mg/kg), a prototype sulfonylurea, on ANP release and sodium excretion were measured in vivo in a canine model of pacing-induced acute heart failure characterized by acute atrial stretch. Immunoreactivity, in atrial tissue, for ANP and the K(ATP) channel subunit, Kir6.2, was determined using specific antibodies. Results: With increased left atrial pressure in heart failure, plasma levels of ANP increased rapidly and peaked within 25 ± 3 min. Glyburide delayed the time required for peak plasma ANP secretion to 48 ± 5 min. This resulted in reduced natriuresis from 84 ± 17 μEq/min in the absence of glyburide, to 34 ± 9 μEq/min in the presence of glyburide. However, glyburide did not alter the renal natriuretic responsiveness to exogenously administered ANP in normal dogs. In atrial tissue, both ANP and the K(ATP) channel subunit, Kir6.2, displayed strong immunoreactivity and co- localization. Conclusions: Glyburide delays release of ANP in acute heart failure resulting in impaired natriuresis. This cannot be ascribed to an antinatriuretic effect on the kidney, but rather may be due to interference with K(ATP) channel-dependent ANP secretion from the atrium. Such adverse outcome of sulfonylurea drug use could reduce the compensatory capacity to preserve cardiorenal homeostasis in acute heart failure. (C) 2000 European Society of Cardiology.
- ATP-sensitive K channel
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine