Relaxant effects of the soluble guanylate cyclase activator and NO sensitizer YC-1 in piglet pulmonary arteries.
BACKGROUND
The indazole derivative YC-1 has been characterized as a nitric oxide (NO)-independent and heme dependent soluble guanylate cyclase (sGC) activator, which also sensitizes sGC to NO.


OBJECTIVE
To examine the effects of YC-1 on vascular relaxation in newborn and 2-week-old piglet pulmonary arteries. The effect of YC-1 on the relaxation induced by exogenous NO was also analyzed.


METHODS
Isolated rings from third branch pulmonary arteries and fifth-seventh-generation intrapulmonary arterioles were mounted in organ chambers for isometric tension recording. Arteries were precontracted with the thromboxane A2 mimetic U46619.


RESULTS
YC-1 induced relaxation was greater in 2-week-old pulmonary arteries and was abolished by the sGC inhibitor ODQ (10 microM). YC-1 induced relaxation was similar in conduit pulmonary arteries and arterioles. In the 2-week-old conduit pulmonary arteries, the response to YC-1 was significantly reduced when the endothelium was removed or after incubation with the NO synthase inhibitor L-NAME (0.1 mM). YC-1 augmented NO-induced relaxation in 2-week-old but not in neonatal conduit pulmonary arteries.


CONCLUSIONS
Our results indicate that YC-1 induced pulmonary vascular relaxation in conduit and resistance pulmonary arteries and these effects increased with postnatal age. In the 2-week-old conduit pulmonary arteries and besides being a direct activator of sGC, YC-1 produced endothelium-dependent relaxation and synergized with exogenous NO.
Department of Pediatrics, University Hospital Maastricht, Research Institute Growth and Development, Maastricht, The Netherlands.
Gema
G
González-Luis
Angel
A
Cogolludo
Laura
L
Moreno
Federica
F
Lodi
Juan
J
Tamargo
Francisco
F
Pérez-Vizcaíno
Eduardo
E
Villamor
D000818:Animals; D000831:Animals, Newborn; D020536:Enzyme Activators / Q000494:pharmacology*; D051604:Guanylate Cyclase-Activating Proteins / Q000378:metabolism*; D007191:Indazoles / Q000494:pharmacology*; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D009569:Nitric Oxide / Q000502:physiology; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011651:Pulmonary Artery / Q000187:drug effects / Q000502:physiology*; D013552:Swine; D014664:Vasodilation / Q000187:drug effects*
D020536:Enzyme Activators; D051604:Guanylate Cyclase-Activating Proteins; D007191:Indazoles; D010975:Platelet Aggregation Inhibitors; C090937:3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole; D009569:Nitric Oxide