L-arginine dependent responses to pressure and vasoactive agents by
isolated pulmonary arteries from monocrotaline-treated rats .
Madden, J. A., P. A. Keller, J. S. Choy, T. A. Alvarez, and A. D.
Hacker.
Research Service, Clement J. Zablocki VA Medical Center and
Departments of Neurology and Medicine, The Medical College of
Wisconsin, Milwaukee WI 53295
APStracts 2:0197A, 1995.
Previously, we found that arterial distensibility ([alpha]) and
responses to KCl, norepinephrine (NE) and angiotensin II (ANG II)
were attenuated in pulmonary arteries from monocrotaline (MCT)
-treated rats (P < 0.05; 13). Although the arteries dilated to
acetylcholine (ACh), presumably by producing nitric oxide (NO),
dilation decreased with time after MCT. To determine if changes in NO
production contribute to the changes in vasoreactivity, intralobar
and sidebranch pulmonary artery segments were dissected from rats 21
days after MCT-treatment, mounted on cannulas and perfused
intraluminally with physiological saline solution at 10 mm Hg.
Changes in vessel diameter in response to 30 mM KCl, NE (10-6 M) or
ANG II (10-9 M) were measured. Intraluminal pressure was raised and
lowered between 2 and 40 mm Hg and diameters measured at each step.
This protocol was repeated in the presence of 1 mM Nw nitro L
-arginine (NLA) and then in the presence of 3 mM L-arginine. Compared
to normal arteries, arteries from MCT-treated rats had decreased
agonist reactivity and [alpha]'s. NLA treatment abolished the ACh
dilation in both artery types but decreased the diameter of
hypertensive arteries more than normals (P<0.05). Agonist responses
were increased in normal arteries but not in hypertensive arteries .
After exposure to L-arginine, the arteries returned to control
diameters and dilated to ACh. Agonist responses returned to nearly
normal levels in control arteries and to less than or equal to
control levels in MCT arteries. The [alpha] increased with NLA
treatment in arteries from normal animals (P<0.05) but not in MCT
arteries. Normal arteries dilated in calcium-free solution (P<0.05)
but hypertensive arteries did not. These results suggest that
pulmonary arteries from rats with MCT-induced pulmonary hypertension
produce more NO than pulmonary arteries from normal rats; inhibiting
NO in the hypertensive arteries does not increase contractile
responses; and the decreased vasoreactivity and [alpha]'s are not due
to increased smooth muscle cell tone but may be due to abnormal
vascular remodeling.
Received 16 November 1994; accepted in final form 22 March 1995.
APS Manuscript Number A1171-4.
Article publication pending Journal of Applied Physiology.
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 16 May 1995.