Vol. 293, Issue 3, 852-860, June 2000

Selective Vasopressin, Angiotensin II, or Dual Receptor Blockade with Developing Congestive Heart Failure¹

Mark J. Clair, Mary K. King, Aron T. Goldberg, Jennifer W. Hendrick, Riccardo Nisato, David M. Gay, Allison E. Morrison, James H. McElmurray, III, R. Stephen Krombach, Brian R. Bond, Catherine Cazaubon, Dino Nisato and Francis G. Spinale

Division of Cardiothoracic Surgery, Medical University of South Carolina, Charleston, South Carolina (M.C., M.K., A.G., J.H., R.N., D.G., A.M., J.M., R.K., B.B., F.S.); and Cardiovascular/Thrombosis Research Department, Sanofi-Synthelabo, Montpellier, France (C.C., D.N.)

With developing congestive heart failure (CHF), activation of the vasopressin V_1a and angiotensin II type 1 (AT₁) receptors can occur. In the present study, we examined the direct effects of V_1a receptor blockade (V_1a block), selective AT₁ receptor blockade (AT₁ block), and dual V_1a/AT₁ receptor blockade (dual block) with respect to left ventricular (LV) function and contractility during the progression of CHF. LV and myocyte functions were examined in pigs with pacing CHF (rapid pacing, 240 beats/min, 3 weeks, n = 10), pacing CHF with concomitant V_1a block (SR49059, 60 mg/kg, n = 8), pacing CHF with concomitant AT₁ block (irbesartan, 30 mg/kg, n = 7), or pacing CHF with dual block (n = 7). LV end-diastolic dimension and peak wall stress were reduced in all receptor blockade groups compared with CHF values. However, LV fractional shortening was increased only in the dual block group compared with CHF values (29 ± 3 versus 21 ± 2, P < .05). Basal LV myocyte percent shortening increased in the dual block group compared with CHF values (3.44 ± 0.23 versus 2.88 ± 0.11, P < .05). Although V_1a or AT₁ block reduced LV loading conditions, only dual block resulted in improved LV and myocyte shortening.