Congestive heart failure is associated with chronotropic and inotropic hyporesponsiveness to adrenergic stimulation. A decrease in Gsα or an increase in G1α is associated with a decrease in adenylyl cylase activity. The current study assessed G proteins in response to treatment with direct-acting vasodilators and correlated changes in lymphocyte β-adrenergic receptor components with changes in hemodynamic variables. Twenty-three patients with severe chronic congestive heart failure (New York Heart Association functional classes III and IV) were studied. Patients were grouped as responders (n = 10) or nonresponders (n = 13) on the basis of clinical assessment of functional status from questionnaires. Therapy was associated with an increase in cardiac index, a decrease in mean arterial pressure, and a decrease in systemic vascular resistance in all patients. Left ventricular filling pressure significantly decreased in responders (26 ± 2 mm to 13 ± 3 mm, p < 0.05) but did not change significantly in nonresponders. Similarly, mean right atrial pressure significantly decreased in responders (11 ± 2 mm Hg to 4 ± 1 mm Hg, p < 0.05) but did not change in nonresponders. Plasma norepinephrine increased significantly only in nonresponders (679 ± 100 pg/ml to 1233 ± 201 pg/ml, p < 0.05). Whereas lymphocyte β-adrenergic receptor density and Gs did not significantly change, Gi increased after treatment only in the nonresponder group (23 ± 5 to 51 ± 11 fmol/mg, p < 0.05). A poor response to direct-acting vasodilators can be distinguished by reactive increases in plasma norepinephrine and lymphocyte Gi in the absence of a decrease in either left- or right-sided filling pressures.
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine