Enhanced Vascular Effects of Cyclic GMP in Septic Rat Aorta
Abstract
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 and from septic rats. Acetylcholine-induced increases in cGMP content were significantly greater in aortas from sham than aortas from septic rats. Maximal contractile performance by aortas from septic rats was impaired whether contractions were induced by the alpha 1 receptor agonist norepinephrine or by KCI depolarization. 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 KCI. 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 is not sepsis is not mediated by altered cGMP levels, but rather that enhanced sensitivity to effects of cGMP may contribute to the disorder. Reprints.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jan 01, 1988
- Accession Number
- ADA201775
Entities
People
- Thomas M. Mckenna
Organizations
- Naval Medical Research Center