TY - JOUR
T1 - Differential effects of natriuretic peptides and NO on LV function in heart failure and normal dogs
AU - Hart, Chaki Y.T.
AU - Hahn, Eugenia L.
AU - Meyer, Donna M.
AU - Burnett, John C.
AU - Redfield, Margaret M.
PY - 2001
Y1 - 2001
N2 - β-Adrenergic hyporesponsiveness in congestive heart failure (CHF) is mediated, in part, by nitric oxide (NO). NO and brain natriuretic peptide (BNP) share cGMP as a second messenger. Left ventricular (LV) function and inotropic response to intravenous dobutamine (Dob) were assessed during sequential intracoronary infusion of saline, HS-142-1 (a BNP receptor antagonist), and HS-142-1 + NG-monomethyl-L-arginine (L-NMMA) in anesthetized dogs with CHF due to rapid pacing and in normal dogs during intracoronary infusion of saline, exogenous BNP, and sodium nitroprusside (SNP). In CHF dogs, intracoronary HS-142-1 did not alter the inotropic response to Dob [percent change in first derivative of LV pressure (%ΔdP/dt) 47 ± 4% saline vs. 54 ± 7% HS-142-1, P = not significant]. Addition of intracoronary L-NMMA to HS-142-1 enhanced the response to Dob (%ΔdP/dt 73 ± 8% L-NMMA + HS-142-1, P < 0.05 vs. H142-1). In normal dogs, intracoronary SNP blunted the inotropic response to Dob (%ΔdP/dt 93 ± 6% saline vs. 71 ± 5% SNP, P < 0.05), whereas intracoronary BNP had no effect. In CHF dogs, the time constant of LV pressure decay during isovolumic relaxation increased with intracoronary HS-142-1 (48 ± 4 ms saline vs. 58 ± 5 ms HS-142-1, P < 0.05) and further increased with intracoronary L-NMMA (56 ± 6 ms HS-142-1 vs. 66 ± 7 ms L-NMMA + HS-142-1, P < 0.05). Endogenous BNP and NO preserve diastolic function in CHF, whereas NO but not BNP inhibits β-adrenergic responsiveness.
AB - β-Adrenergic hyporesponsiveness in congestive heart failure (CHF) is mediated, in part, by nitric oxide (NO). NO and brain natriuretic peptide (BNP) share cGMP as a second messenger. Left ventricular (LV) function and inotropic response to intravenous dobutamine (Dob) were assessed during sequential intracoronary infusion of saline, HS-142-1 (a BNP receptor antagonist), and HS-142-1 + NG-monomethyl-L-arginine (L-NMMA) in anesthetized dogs with CHF due to rapid pacing and in normal dogs during intracoronary infusion of saline, exogenous BNP, and sodium nitroprusside (SNP). In CHF dogs, intracoronary HS-142-1 did not alter the inotropic response to Dob [percent change in first derivative of LV pressure (%ΔdP/dt) 47 ± 4% saline vs. 54 ± 7% HS-142-1, P = not significant]. Addition of intracoronary L-NMMA to HS-142-1 enhanced the response to Dob (%ΔdP/dt 73 ± 8% L-NMMA + HS-142-1, P < 0.05 vs. H142-1). In normal dogs, intracoronary SNP blunted the inotropic response to Dob (%ΔdP/dt 93 ± 6% saline vs. 71 ± 5% SNP, P < 0.05), whereas intracoronary BNP had no effect. In CHF dogs, the time constant of LV pressure decay during isovolumic relaxation increased with intracoronary HS-142-1 (48 ± 4 ms saline vs. 58 ± 5 ms HS-142-1, P < 0.05) and further increased with intracoronary L-NMMA (56 ± 6 ms HS-142-1 vs. 66 ± 7 ms L-NMMA + HS-142-1, P < 0.05). Endogenous BNP and NO preserve diastolic function in CHF, whereas NO but not BNP inhibits β-adrenergic responsiveness.
KW - Inotropy
KW - Lusitropy
KW - cGMP
UR - http://www.scopus.com/inward/record.url?scp=0034803922&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0034803922&partnerID=8YFLogxK
U2 - 10.1152/ajpheart.2001.281.1.h146
DO - 10.1152/ajpheart.2001.281.1.h146
M3 - Article
C2 - 11406479
AN - SCOPUS:0034803922
SN - 0363-6135
VL - 281
SP - H146-H154
JO - American Journal of Physiology
JF - American Journal of Physiology
IS - 1 50-1
ER -