Pulmonary arterial endothelial dysfunction potentiates hypercapnic vasoconstriction and alters the response to inhaled nitric oxide.
BACKGROUND
Pulmonary hypertensive crisis can be initiated by episodes of hypercapnic acidosis. Hypercapnic vasoconstriction in the newborn pulmonary arterial circulation may be modulated by endogenous production of nitric oxide (NO) by the endothelial cell and effectively treated with inhalation of NO.


METHODS
Sixteen 48-hour-old piglets were randomized to receive a hypercapnic challenge after administration of either saline vehicle or the NO synthase inhibitor N-omega-nitro-L-arginine (L-NA). Pulmonary arterial pressure, flow, and radius measurements were taken at baseline, after infusion of vehicle or L-NA, during hypercapnia (inspired fraction of carbon dioxide, 0.15), and during inhalation of NO (100 ppm). Fourier analysis was used to calculate input mean impedance, reflecting distal arteriolar vasoconstriction, and characteristic impedance, reflecting proximal arterial geometry and distensibility.


RESULTS
Input mean impedance was increased with L-NA administration. Animals pretreated with L-NA also underwent a much larger increase in input mean impedance with exposure to hypercapnia than untreated animals. Characteristic impedance increased in the treated animals, but not in the controls.


CONCLUSIONS
In the newborn pulmonary arterial circulation, endogenous NO production by the endothelial cell modulates resting tone distally, but not proximally. In addition, lack of a functional endothelium markedly potentiates the distal vasoconstrictor response to hypercapnia and produces proximal vasoconstriction. Despite impaired endothelial function, inhaled NO remains an effective vasodilator in hypercapnic pulmonary vasoconstriction.
Myers
J L
JL
Department of Surgery, Georgetown University Medical Center, Washington, DC, USA.
Wizorek
J J
JJ
Myers
A K
AK
Yankah
E
E
Pettit
M T
MT
Kouretas
P C
PC
Dalton
H J
HJ
Wang
Y
Y
Hopkins
R A
RA
D000280:Administration, Inhalation; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects; D002245:Carbon Dioxide / Q000097:blood; D004730:Endothelium, Vascular / Q000503:physiopathology*; D006935:Hypercapnia / Q000097:blood / Q000503:physiopathology*; D009569:Nitric Oxide / Q000008:administration & dosage / Q000494:pharmacology*; D019335:Nitroarginine / Q000494:pharmacology; D010100:Oxygen / Q000097:blood; D011651:Pulmonary Artery / Q000503:physiopathology*; D013552:Swine; D014655:Vascular Resistance / Q000187:drug effects; D014661:Vasoconstriction
D002245:Carbon Dioxide; D019335:Nitroarginine; D009569:Nitric Oxide; D010100:Oxygen