Relaxant Effects of Carbon Monoxide Compared with Nitric Oxide in Pulmonary and Systemic Vessels of Newborn Piglets

Abstract

Nitric oxide (NO) has been implicated in a number of diverse physiologic processes, including regulation of vascular tone. Carbon monoxide (CO) is another endogenously generated diatomic gas that may play an important physiologic role in vascular smooth muscle homeostasis. The purpose of this study was to compare the responses to exogenous NO and CO in isolated vessels (pulmonary arteries, pulmonary veins, and mesenteric arteries) from 12-to 24-h-old and 2-wk-old piglets. Vessels precontracted with the thromboxane A 2 mimetic U46619 (10 Ϫ7 M) relaxed in response to CO (2 ϫ 10 Ϫ6 to 2 ϫ 10 Ϫ4 M) and NO (2 ϫ 10 Ϫ9 to 2 ϫ 10 Ϫ7 M); these effects were not affected by endothelium removal but were completely abolished by the soluble guanylate cyclase inhibitor ODQ (10 Ϫ5 M). In pulmonary arteries, the maximal relaxation to NO increased with postnatal age from 33 Ϯ 4% of the precontraction value to 56 Ϯ 5%, in 12-to 24-h-old and 2-week-old piglets, respectively (p Ͻ 0.01), but the response to CO decreased from 25 Ϯ 3% to 12 Ϯ 1%, respectively (p Ͻ 0.01). The maximal response to CO was greater in pulmonary veins than in pulmonary or mesenteric arteries for both age groups (p Ͻ 0.01). Vasorelaxation induced by endogenous NO (stimulated by acetylcholine) was also greater in pulmonary veins when compared with pulmonary arteries and increased with postnatal age in both vessels. In contrast, no age-related differences were observed in the vasorelaxation induced by the cGMP analog 8-bromo cGMP in pulmonary arteries. When the response to NO was analyzed under three different extracellular O 2 concentrations (PO 2 4.51 Ϯ 0.03, 19.32 Ϯ 0.17, and 86 Ϯ 0.62, kPa), no significant differences were found. However, in the presence of superoxide dismutase (100 U/mL). the response to CO remained unchanged, and the response to NO improved in pulmonary arteries from 2-week-old but not from newborn piglets. In conclusion, both NO and CO relaxed neonatal vessels through soluble guanylate cyclase activation. However, when compared with NO, CO exhibited a poor vasorelaxant activity. Pulmonary vasorelaxation induced by NO increased with postnatal age, whereas that induced by CO decreased. Changes in extracellular oxygen concentration did not alter the pulmonary vascular response to NO. However, the presence of superoxide dismutase improved the response to NO, indicating that oxidant activity limits the vasorelaxant response to NO but not to CO. (Pediatr Res 48: 546-553, 2000) Abbreviations NO, nitric oxide CO, carbon monoxide sGC, soluble guanylate cyclase HO, heme oxygenase SOD, superoxide dismutase U46619, 9,11-dideoxy-11␣,9␣-epoxymethano-prostaglandinNO is known to be involved in the regulation of multiple physiologic processes, including the regulation of pulmonary vascular tone (1). On the other hand, another diatomic gas, CO, traditionally considered as a toxic pollutant, poisons by binding to the iron-containing heme group found in Hb and other enzymes (2). Recently, evidence is accumulating that CO can be also a physiologic endogenous ...

Cellular mechanisms of thromboxane A2-mediated contraction in pulmonary veins

“…Our results indicate that U-46619 contraction is mediated by: 1) Ca 2ϩ influx via L-type voltage-gated Mechanisms of U-46619 contraction have been investigated in a number of smooth muscle preparations. Although U-46619 is well known to cause contraction in pulmonary veins, most investigators have simply utilized U-46619 to precontract pulmonary veins before assessing responses to putative vasorelaxants (7,8,34). U-46619 has been shown to constrict human pulmonary veins harvested during lung cancer surgery via activation of TXA 2 -selective prostanoid receptors (35).…”

Hyperosmolar Solution Effects in Guinea Pig Airways. III. Studies on the Identity of Epithelium-Derived Relaxing Factor in Isolated Perfused Trachea Using Pharmacological Agents

“…Recognition of the vascular and airway smooth muscle relaxant effects of carbon monoxide (CO; Maines, 1997;Villamor et al, 2000;Kinhult et al, 2001) prompted an examination of its possible role in hyperosmolarity-induced relaxation. Hemoglobin (ferrous), which scavenges CO with high affinity, evoked a modest contraction when added to the baths, which could suggest basal release of CO. Hemoglobin had no effect on the transient contractile phase of response to D-M ; not shown) but inhibited the relaxation to D-M (Fig.…”

Haem oxygenase augments porcine granulosa cell apoptosis in vitro

“…It has a role similar to that of nitric oxide (NO) in some organs: it is considered to be a neurotransmitter like NO in the central nervous system (Costa et al 1996, Kim & Rivier 2000, and both CO and NO stimulate the action of soluble guanylate cyclase, thereby promoting smooth muscle relaxation and vasodilatation in the cardiovascular system (Villamor et al 2000). CO is produced endogenously, mainly from the degeneration of haem by haem oxygenases (Maines 1988).…”

“…Some investigators have also found that the NO/nitric oxide synthase (NOS) system inhibits steroid production and P450 aromatase activity in human luteal granulosa cells and in porcine granulosa cells (PGCs) (Van Voorhis et al 1994, Masuda et al 1997. As CO and NO have similar cellular functions in several organ systems, including the central nervous system (Kim & Rivier 2000) and the cardiovascular system (Villamor et al 2000), the CO/haem oxygenase system also may be involved in the follicular development of the ovaries.…”