Key Points
- To determine whether nitric oxide and cyclic GMP mediate endothelium-independent nonadrenergic, noncholinergic relaxation in guinea-pig pulmonary arteries.
- Mounted endothelium-denuded guinea-pig branch pulmonary artery rings precontracted with U44069 and subjected them to electric field stimulation (1–24 Hz) under adrenergic and cholinergic blockade.
- Assessed relaxant responses in the presence of nitric oxide synthase inhibitors (L-NMMA, L-NAME), a guanylyl cyclase inhibitor (methylene blue), phosphodiesterase inhibitors (zaprinast, zardaverine), and superoxide modulators.
- Quantified tissue cyclic GMP content following electric field stimulation and evaluated the effects of chemical sympathectomy with 6-hydroxydopamine.
- Electric field stimulation (16 Hz) induced relaxation that was inhibited by L-NMMA (53 ± 5%), L-NAME (74 ± 9%), and methylene blue (82 ± 9%) (n = 5–7, P < 0.01 compared with control), with L-NMMA inhibition reversed by L-arginine but not D-arginine.
- Electric field stimulation at 16 Hz produced a 3-fold increase in tissue cyclic GMP that was prevented by L-NMMA, and relaxation at 4 Hz was selectively potentiated by the cyclic GMP phosphodiesterase inhibitor zaprinast.
- Sympathetic denervation using 6-hydroxydopamine did not alter electric field stimulation-induced relaxation, confirming mediation by nonadrenergic nerve endings.
Structured PICO
PPopulationGuinea-pig branch pulmonary artery (PA) rings denuded of endothelium
IInterventionElectric field stimulation (EFS) in the presence of NO synthase inhibitors (L-NMMA, L-NAME) and guanylyl cyclase inhibitor (methylene blue)
OOutcomeRelaxation of U44069-precontracted PA ringssurrogate
Nitric oxide released from intramural nerve endings mediates nonadrenergic, noncholinergic vasodilatation in guinea-pig pulmonary arteries via activation of guanylyl cyclase.