Carbon monoxide formation in the ductus arteriosus in the lamb: implications for the regulation of muscle tone

Coceani, Flavio; Kelsey, Lois; Seidlitz, Eric; Marks, Gerald S.; McLaughlin, Brian E.; Vreman, Hendrik J.; Stevenson, David K.; Rabinovitch, Marlene; Ackerley, Cameron

doi:10.1038/sj.bjp.0700947

Cited by 106 publications

(61 citation statements)

References 38 publications

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“…If so, it might be expected that carbon monoxide could block basal nitric oxide production and cause vasoconstriction with a consequent increase in blood pressure. While these two functionally opposing roles of endogenously formed carbon monoxide in vascular tone are equally plausible, several studies using isolated vessels and perfused preparations (7,(53)(54)(55)(56) have suggested that hemederived carbon monoxide may be vasodilatory. Such reports have understandably typified carbon monoxide as a vasodilator.…”

Section: Endogenous Carbon Monoxide and Vascular Tone: Dual Actions Cmentioning

confidence: 99%

Carbon monoxide: from toxin to endogenous modulator of cardiovascular functions

Johnson

Kozma

Colombari

1999

Braz J Med Biol Res

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Carbon monoxide (CO) is a pollutant commonly recognized for its toxicological attributes, including CNS and cardiovascular effects. But CO is also formed endogenously in mammalian tissues. Endogenously formed CO normally arises from heme degradation in a reaction catalyzed by heme oxygenase. While inhibitors of endogenous CO production can raise arterial pressure, heme loading can enhance CO production and lead to vasodepression. Both central and peripheral tissues possess heme oxygenases and generate CO from heme, but the inability of heme substrate to cross the blood brain barrier suggests the CNS heme-heme oxygenase-CO system may be independent of the periphery. In the CNS, CO apparently acts in the nucleus tractus solitarii (NTS) promoting changes in glutamatergic neurotransmission and lowering blood pressure. At the periphery, the heme-heme oxygenase-CO system can affect cardiovascular functions in a two-fold manner; specifically: 1) heme-derived CO generated within vascular smooth muscle (VSM) can promote vasodilation, but 2) its actions on the endothelium apparently can promote vasoconstriction. Thus, it seems reasonable that the CNS-, VSM-and endothelial-dependent actions of the heme-heme oxygenase-CO system may all affect cardiac output and vascular resistance, and subsequently blood pressure.

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Section: Endogenous Carbon Monoxide and Vascular Tone: Dual Actions Cmentioning

confidence: 99%

Carbon monoxide: from toxin to endogenous modulator of cardiovascular functions

Johnson

Kozma

Colombari

1999

Braz J Med Biol Res

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“…Concentrations of the inhibitors were derived from the literature with the aim of combining efficacy with selectivity. In particular, at the stated concentrations, ZnPP exerts a specific effect on the HO enzyme complex in the ductus (21).…”

Section: Animalsmentioning

confidence: 99%

Role of Microsomal Prostaglandin E Synthase-1 (mPGES1)-Derived PGE2 in Patency of the Ductus Arteriosus in the Mouse

et al. 2008

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Prostaglandin E 2 (PGE 2 ) plays a key role in the ductus arteriosus, prenatally by maintaining patency and postnatally by promoting tissue remodeling for closure. Here, by using near-term mouse fetuses with (wild-type, WT) and without microsomal PGE synthase-1 (mPGES1Ϫ/Ϫ), we have examined the importance of this enzyme for PGE 2 formation and function. mPGES1Ϫ/Ϫ ductus, unlike WT ductus, contracted little, or not all, to indomethacin in vitro. Coincidentally, as evident from responses to N G -nitro-Larginine methyl ester and zinc photoporphyrin, the mutant showed no significant enhancement of nitric oxide (NO)-and carbon monoxide (CO)-based relaxation. mPGES1 suppression differs, therefore, from cyclooxygenase (COX) suppression, whether genetically or pharmacologically induced, where NO is markedly up-regulated. In vivo, the ductus was patent, albeit occasionally with a narrowed lumen, in all mPGES1Ϫ/Ϫ fetuses. Conversely, postnatal closure progressed regularly in mPGES1Ϫ/Ϫ animals thanks to residual PGE 2 originating via mPGES2. We conclude that mPGES1 is critical for PGE 2 formation in the ductus but its loss does not entail compensatory upregulation of other relaxing mechanisms. Accordingly, an mPGES1 inhibitor stands out as a prospective better tool, compared with the currently used COX inhibitors, for the management of premature infants with persistent ductus. (Pediatr Res 64: 523-527, 2008) P rostaglandin (PG) E 2 is viewed as the prime agent for prenatal patency of the ductus arteriosus (1). Conversely, PGI 2 is without a role, notwithstanding its occurrence in the vessel and its known importance for vasoregulation elsewhere (2,3). Ductal PGE 2 is formed primarily through the cyclooxygenase-2 (COX2)/microsomal PGE synthase-1 (mPGES1) complex, while little of the compound originates from the COX1/mPGES1 complex and none at all from cytosolic PGES (cPGES). No information is available on microsomal PGE synthase-2 (mPGES2), but evidence from other vascular districts points to its minor function (4). Several findings support this arrangement in the ductus, namely, immunocytochemical data showing a predominant colocalization of COX2 with mPGES1 (5); the increase in COX2 and mPGES1 expression occurring selectively through development (6); the constrictor action of COX2 inhibitors on the ductus, being close or even equal in magnitude to that of a dual COX1/ COX2 inhibitor (7-9); the greater impairment of PGE 2 -based relaxation upon COX2 than COX1 deletion (5) along with the marked curtailment of PGE 2 formation after inhibition of either COX2 or mPGES1 (6,7). Consistent with the preferential operation of the COX2/mPGES1 route for PGE 2 synthesis is also evidence from adult blood vessels (10) and the notion that mPGES1 is catalytically most active among the PGES (11).Despite these facts, previous attempts to prove the actual importance of the COX2/mPGES1 pathway for ductus patency have failed. As shown by others and ourselves (5,12,13), COX2 removal does not result in loss of patency, likely thanks to ...

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“…Furchgott and Jothianandan (1991) reported that CO, arising from the metabolism of heme by HO, dilated blood vessels, whereas inhibition of HO by tinmesoporphyrin (SnMP) produced vasoconstriction (Kozma et al, 1999) and raised blood pressure (Johnson et al, 1995(Johnson et al, , 1996. Heme, by activating HO, has been shown to dilate the ductus arteriosus (Coceani et al, 1997). Moreover, contiguous, if not overlapping, spheres of activity within the vasculature of nitric oxide (NO) and CO were suggested by the study of Zakhary et al (1996).…”

mentioning

confidence: 99%

Role of the Heme Oxygenases in Abnormalities of the Mesenteric Circulation in Cirrhotic Rats

Sacerdoti

Abraham²,

Oyekan³

et al. 2003

J Pharmacol Exp Ther

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Carbon monoxide (CO), a product of heme metabolism by heme-oxygenase (HO), has biological actions similar to those of nitric oxide (NO). The role of CO in decreasing vascular responses to constrictor agents produced by experimental cirrhosis induced by carbon tetrachloride was evaluated before and after inhibition of HO with tin-mesoporphyrin (SnMP) in the perfused superior mesenteric vasculature (SMV) of cirrhotic and normal rats and in normal rats transfected with the human HO-1 (HHO-1) gene. Perfusion pressure and vasoconstrictor responses of the SMV to KCl, phenylephrine (PE), and endothelin-1 (ET-1) were decreased in cirrhotic rats. SnMP increased SMV perfusion pressure and restored the constrictor responses of the SMV to KCl, PE, and ET-1 in cirrhotic rats. The relative roles of NO and CO in producing hyporeactivity of the SMV to PE in cirrhotic rats were examined. Vasoconstrictor responses to PE were successively augmented by stepwise inhibition of CO and NO production, suggesting a complementary role for these gases in the regulation of reactivity of the SMV. Expression of constitutive but not of inducible HO (HO-1) was increased in the SMV of cirrhotic rats as was HO activity. Administration of adenovirus containing HHO-1 gene produced detection of HHO-1 RNA and increased HO activity in the SMV within 7 days. Rats transfected with HO-1 demonstrated reduction in both perfusion pressure and vasoconstrictor responses to PE in the SMV. We propose that HO is an essential component in mechanisms that modulate reactivity of the mesenteric circulation in experimental hepatic cirrhosis in rats.

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Carbon monoxide formation in the ductus arteriosus in the lamb: implications for the regulation of muscle tone

Cited by 106 publications

References 38 publications

Carbon monoxide: from toxin to endogenous modulator of cardiovascular functions

Carbon monoxide: from toxin to endogenous modulator of cardiovascular functions

Role of Microsomal Prostaglandin E Synthase-1 (mPGES1)-Derived PGE2 in Patency of the Ductus Arteriosus in the Mouse

Role of the Heme Oxygenases in Abnormalities of the Mesenteric Circulation in Cirrhotic Rats

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