Altered endothelium-dependent responses in lambs with pulmonary
hypertension and increased pulmonary blood flow.
Reddy, V. Mohan, Jackson Wong, John R. Liddicoat, Michael Johengen,
Roger Chang, Jeffrey R. Fineman.
Departments of Cardiothoracic Surgery* and Pediatrics, University
of California San Francisco, San Francisco, CA 94143-0106
APStracts 3:0064H, 1996.
To investigate early endothelial function associated with increased
pulmonary blood flow, vascular shunts were placed between the
ascending aorta and main pulmonary artery in 18 late gestation fetal
sheep. Four weeks after delivery, the lambs were instrumented to
measure vascular pressures and blood flows, and blood was collected
to measure plasma concentrations of cGMP (the second messenger to NO
-mediated vasodilation) and l-arginine (the precursor for NO
synthesis). The responses to the endothelium-dependent vasodilators-
-acetylcholine (ACH, 1.0 [mu]cg/kg) and ATP (0.1 mg/kg/min), the
endothelium-independent vasodilators--M&B 22948 (a cGMP specific
phosphodiesterase inhibitor, 2.5 mg/kg) and inhaled nitric oxide (NO,
40 ppm), and Nw nitro-l-arginine (an inhibitor of nitric oxide
synthase, NOS, 5 mg/kg) were then compared to 12 age-matched
controls. Vasodilator responses in control lambs were determined
during pulmonary hypertension induced by U46619 (a thromboxane A2
mimic). Shunted lambs displayed a selective impairment of
endothelium-dependent pulmonary vasodilation, an augmented pulmonary
vasoconstricting response to NOS inhibition, increased plasma cGMP
concentrations and decreased l-arginine concentrations. Taken
together, these data suggests that lambs with pulmonary hypertension
and increased pulmonary blood flow have early aberrations in
endothelial function, as manifested by increased basal NO activity
that cannot be further increased by agonist-induced endothelium
-dependent vasodilators.
Received 10 September 1995; accepted in final form 24 November
1996.
APS Manuscript Number H851-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 8 February 96