PLASMA CYCLIC GUANOSINE-MONOPHOSPHATE IN CHRONIC HEART-FAILURE - HEMODYNAMIC AND NEUROHORMONAL CORRELATIONS AND RESPONSE TO NITRATE THERAPY

This study evaluated the relation between plasma cyclic guanosine mono phosphate (cGMP) and hemodynamic and neurohormonal parameters in patie nts with chronic congestive heart failure and assessed the effect of o rganic nitrate on plasma cGMP levels. Plasma cGMP was fourfold higher in 18 patients with congestive heart failure compared with 15 control subjects (16.7 +/- 9.7 versus 4.0 +/- 1.0 pmol/ml; p < 0.0001) but did not correlate with plasma levels of catecholamines, renin, atrial nat riuretic peptide, or with baseline hemodynamic values. The administrat ion of a hemodynamically effective dose of oral isosorbide dinitrate ( 40 mg) resulted in a transient reduction in plasma CGMP from 16.7 +/- 9.7 pmol/ml at baseline to 13.0 +/- 6.6 pmol/ml at 1 hour (p < 0.05). This change was associated with small and statistically insignificant changes in neurohormonal values and had no relation to any of the hemo dynamic changes. We concluded that (1) elevated plasma cGMP in congest ive heart failure does not correlate with other neurohormonal or hemod ynamic parameters and may be an independent parameter of heart failure , (2) in contrast to previously documented nitrate-mediated increases in intracellular cGMP, nitrate therapy results in a reduction in plasm a cGMP, and (3) changes in plasma cGMP cannot serve as a surrogate mea surement of changes in intracellular cGMP.