AJP - Regulatory, Integrative and Comparative Physiology, Vol 254, Issue 3 436-R442, Copyright © 1988 by American Physiological Society
Enhanced vascular effects of cyclic GMP in septic rat aorta
T. M. McKenna
Surgical Research Division, Naval Medical Research Institute, Bethesda, Maryland 20814-5055.
The modulation of vascular function by guanosine 3',5'-cyclic monophosphate
(cGMP) in sepsis was examined in isolated rat aortas. Basal cGMP content
was similar in aortas from sham-operated [3.6 +/- 0.8 (SE) pmol cGMP/mg
protein] and from septic (3.2 +/- 1.0) rats. Acetylcholine-induced
increases in cGMP content were significantly greater in aortas from sham
(109.7 +/- 31.1) than aortas from septic rats (42.1 +/- 10.6). Maximal
contractile performance by aortas from septic rats was impaired whether
contractions were induced by the alpha 1-receptor agonist norepinephrine
(497 +/- 49 mg tension/mg tissue vs. sham 749 +/- 43) or by KCl
depolarization (265 +/- 31 vs. sham 613 +/- 79). Aortas from septic rats
also exhibited a rightward-shifted dose response to norepinephrine.
Inhibition of endogenous cGMP production by myoglobin or methylene blue
treatment disproportionally improved responses by aortas from septic rats
to both norepinephrine and KCl. In contrast, exposure of aortas to
exogenous 8-bromo-cGMP engaged exaggerated vasodilatory responses in tissue
from septic animals. Aortas from sham and septic rats contracted equally to
stimulation by phorbol 12,13-dibutyrate. These findings indicate that
reduced vascular contraction in sepsis is not mediated by altered cGMP
levels, but rather that enhanced sensitivity to effects of cGMP may
contribute to the disorder.
