Lymphocyte G proteins reflect response to treatment in congestive heart failure.
Congestive heart failure is associated with chronotropic and inotropic hyporesponsiveness to adrenergic stimulation. A decrease in Gs alpha or an increase in Gi alpha is associated with a decrease in adenylyl cyclase activity. The current study assessed G proteins in response to treatment with direct-acting vasodilators and correlated changes in lymphocyte beta-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 beta-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.
Horn
E M
EM
Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, N.Y.
Kukin
M L
ML
Neuberg
G W
GW
Goldsmith
R L
RL
McCarty
M
M
Gratch
M
M
Medina
N
N
Yushak
M
M
Packer
M
M
Bilezikian
J P
JP
D000368:Aged; D002908:Chronic Disease; D000242:Cyclic AMP / Q000097:blood; D005260:Female; D019204:GTP-Binding Proteins / Q000032:analysis / Q000187:drug effects / Q000378:metabolism*; D006333:Heart Failure / Q000097:blood* / Q000188:drug therapy / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D008214:Lymphocytes / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000097:blood; D011869:Radioligand Assay / Q000379:methods; D011943:Receptors, Adrenergic, beta / Q000032:analysis / Q000187:drug effects / Q000378:metabolism; D014665:Vasodilator Agents / Q000627:therapeutic use
D011943:Receptors, Adrenergic, beta; D014665:Vasodilator Agents; D000242:Cyclic AMP; D019204:GTP-Binding Proteins; D009638:Norepinephrine