Selective vasopressin, angiotensin II, or dual receptor blockade with developing congestive heart failure.
With developing congestive heart failure (CHF), activation of the vasopressin V(1a) and angiotensin II type 1 (AT(1)) receptors can occur. In the present study, we examined the direct effects of V(1a) receptor blockade (V(1a) block), selective AT(1) receptor blockade (AT(1) block), and dual V(1a)/AT(1) 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 AT(1) 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 AT(1) block reduced LV loading conditions, only dual block resulted in improved LV and myocyte shortening.
Clair
M J
MJ
Division of Cardiothoracic Surgery, Medical University of South Carolina, Charleston 29425, USA.
King
M K
MK
Goldberg
A T
AT
Hendrick
J W
JW
Nisato
R
R
Gay
D M
DM
Morrison
A E
AE
McElmurray
J H
JH
Krombach
R S
RS
Bond
B R
BR
Cazaubon
C
C
Nisato
D
D
Spinale
F G
FG
D000804:Angiotensin II / Q000097:blood / Q000494:pharmacology; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D065092:Antidiuretic Hormone Receptor Antagonists; D009320:Atrial Natriuretic Factor / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D012964:Sodium / Q000097:blood; D013552:Swine; D014667:Vasopressins / Q000097:blood / Q000494:pharmacology; D016277:Ventricular Function, Left / Q000187:drug effects
D057911:Angiotensin Receptor Antagonists; D065092:Antidiuretic Hormone Receptor Antagonists; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D014667:Vasopressins; D000804:Angiotensin II; D009320:Atrial Natriuretic Factor; D012964:Sodium