Nesiritide acutely increases pulmonary and systemic levels of nitric oxide in patients with pulmonary hypertension.
BACKGROUND
Pulmonary hypertension (PH) is characterized by decreased pulmonary vascular expression of nitric oxide (NOx), a vasodilator that increases levels of smooth muscle cyclic guanosine monophosphate (cGMP). This study investigated mechanisms by which the vasodilator B-type natriuretic peptide (BNP) affects the systemic and pulmonary vasculature in PH patients.


RESULTS
Twenty PH patients with mean pulmonary artery (PA) pressure > 25 mm Hg were enrolled. Ten had precapillary (pulmonary capillary wedge pressure [PCWP] < or = 15 mm Hg) and 10 had postcapillary (PCWP > 15 mm Hg) PH. Right heart catheterization was performed before and 30 minutes after intravenous nesiritide infusion. NOx and cGMP levels from the PA and systemic (AO) arteries were obtained before and after nesiritide infusion. The postcapillary PH patients demonstrated significantly reduced pulmonary vascular resistance after nesiritide; there was no change in the precapillary PH cohort. NOx levels increased significantly in both AO (P < .0001) and PA (P = .0093), as did cGMP levels (P < .0001). There was a higher increase in NOx levels from the pulmonary arteries in precapillary PH patients compared to postcapillary PH patients (P = .020).


CONCLUSIONS
In PH patients, nesiritide infusion significantly increases NOx levels, suggesting a novel mechanism for its vasodilatory effects. These responses may differ between pre- and postcapillary PH patients.
Khush
Kiran K
KK
Division of Cardiology, University of California at San Francisco Medical Center, San Francisco, California, USA.
De Marco
Teresa
T
Vakharia
Kalpesh T
KT
Harmon
Cynthia
C
Fineman
Jeffrey R
JR
Chatterjee
Kanu
K
Michaels
Andrew D
AD
D000328:Adult; D000368:Aged; D001158:Arteries; D002196:Capillaries; D015331:Cohort Studies; D006152:Cyclic GMP / Q000097:blood; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D006976:Hypertension, Pulmonary / Q000097:blood* / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D045283:Natriuretic Agents / Q000627:therapeutic use*; D020097:Natriuretic Peptide, Brain / Q000627:therapeutic use*; D009569:Nitric Oxide / Q000097:blood*; D011446:Prospective Studies; D011651:Pulmonary Artery; D011669:Pulmonary Wedge Pressure; D014655:Vascular Resistance / Q000187:drug effects; D014665:Vasodilator Agents / Q000627:therapeutic use*
D045283:Natriuretic Agents; D014665:Vasodilator Agents; D020097:Natriuretic Peptide, Brain; D009569:Nitric Oxide; D006152:Cyclic GMP