Relaxant effects of carbon monoxide compared with nitric oxide in pulmonary and systemic vessels of newborn piglets

Nitric oxide (NO) has been implicated in a number of diverse physiologic pr ocesses, including regulation of vascular tone. Carbon monoxide (CO) is ano ther endogenously generated diatomic gas that may play an important physiol ogic role in vascular smooth muscle homeostasis. The purpose of this study was to compare the responses to exogenous NO and CO in isolated vessels (pu lmonary arteries, pulmonary veins, and mesenteric arteries) from 12- to 24- h-old and 2-wk-old piglets. Vessels precontracted with the thromboxane A, m imetic U46619 (10(-7) M) relaxed in response to CO (2 x 10(-6) to 2 x 10(-4 ) M) and NO (2 x 10(-9) to 2 x 10(-7) M); these effects were not affected b y endothelium removal but were completely abolished by the soluble guanylat e cyclase inhibitor ODQ (10(-5) M). In pulmonary arteries, the maximal rela xation to NO increased with postnatal age from 33 +/- 4% of the precontract ion value to 56 +/- 5%, in 12- to 24-h-old and 2-week-old piglets, respecti vely (p < 0.01), but the response to CO decreased from 25 +/- 3% to 12 +/- 1%, respectively (p < 0.01). The maximal response to CO was greater in pulm onary veins than in pulmonary or mesenteric arteries for both age groups (p < 0.01). Vasorelaxation induced by endogenous NO (stimulated by acetylchol ine) was also greater in pulmonary veins when compared with pulmonary arter ies and increased with postnatal age in both vessels. In contrast, no age-r elated differences were observed in the vasorelaxation induced by the cGMP analog 8-bromo cGMP in pulmonary arteries. When the response to NO was anal yzed under three different extracellular O-2 concentrations (Po-2 4.51 +/- 0.03, 19.32 +/- 0.17, and 86 +/- 0.62, kPa), no significant differences wer e found. However, in the presence of superoxide dismutase (100 U/mL). the r esponse to CO remained unchanged, and the response to NO improved in pulmon ary arteries from 2-week-old but not from newborn piglets. In conclusion, b oth NO and CO relaxed neonatal vessels through soluble guanylate cyclase ac tivation. However, when compared with NO, CO exhibited a poor vasorelaxant activity. Pulmonary vasorelaxation induced by NO increased with postnatal a ge, whereas that induced by CO decreased. Changes in extracellular oxygen c oncentration did not alter the pulmonary vascular response to NO. However, the presence of superoxide dismutase improved the response to NO, indicatin g that oxidant activity limits the vasorelaxant response to NO but not to C O.