Thromboxane mimics the pulmonary but not systemic vascular responses to bolus HCl injections in broiler chickens

Abstract

Bolus i.v. injections of 1.2 N HCl elicit a rapid but transient pulmonary vasoconstriction in broiler chickens. In mammals, the pulmonary vasoconstrictive response to bolus acid injection depends on increased synthesis of thromboxane A2; however, the vascular responsiveness of domestic fowl to thromboxane previously had not been evaluated. In the present study, we tested the hypothesis that, if HCl triggers pulmonary vasoconstriction by stimulating thromboxane A2 synthesis in broilers, then bolus i.v. injections of the potent thromboxane A2 mimetic U44069 (9,11-dideoxy-9alpha,11alpha-epoxy-methanoprostaglandin++ + F2alpha; 1 micromol/mL; 0.5 mL injected volume) should trigger hemodynamic responses similar to those elicited by HCl (1.2 N; 1.5 mL injected volume). Both HCl and the thromboxane mimetic elicited twofold or greater increases in pulmonary vascular resistance, which in turn increased pulmonary arterial pressure by 50% despite concurrent reductions in cardiac output. The reductions in cardiac output were associated with reductions in stroke volume but not heart rate. The thromboxane mimetic also increased the total peripheral resistance, which minimized the reduction in mean systemic arterial pressure associated with the decrease in cardiac output. In contrast, HCl injections did not increase total peripheral resistance; consequently, the reduction in cardiac output caused the mean systemic arterial pressure to decrease by 30 mm Hg. Mannitol (2.5%; 1.5 mL) was injected i.v. as a volume control, and had no influence on any of the variables. This study provides the first direct evidence that thromboxane is a potent pulmonary vasoconstrictor in broilers, and provides support for the hypothesis that thromboxane mediates the pulmonary vasoconstrictive response to bolus i.v. injections of HCl. The differential response of the systemic vasculature to the thromboxane mimetic and HCl may indicate that cardiopulmonary responses to HCl injections are not mediated solely via thromboxane production. Alternatively, a direct dilatory effect of elevated hydrogen ion concentrations on the systemic vasculature may have counteracted any tendency for simultaneously evolved endogenous thromboxane to elicit systemic vasoconstriction.

Broiler pulmonary hypertensive responses during lipopolysaccharide-induced tolerance and cyclooxygenase inhibition

“…The U44069 (Sigma Chemical Co.) was diluted to 1 mM in 2.5% mannitol, and was injected as a 0.05-to 0.1-mL i.v. bolus as described previously (Wideman et al, 1999Chapman and Wideman, 2006b). Previously we demonstrated that neither i.v.…”

“…The mammalian PH response to LPS appears to be mediated primarily by ET-1 and TxA 2 (Morel et al, 1989;Longworth et al, 1994;Faltin et al, 1996;Snapper et al, 1998;Wanecek et al, 2000). Thromboxane A 2 , ET-1, and 5-HT are known to be potent pulmonary vasoconstrictors in chickens (Wideman et al, 1998(Wideman et al, , 1999Martinez-Lemus et al, 1999Wideman, 2002, 2006a,b;Villamor et al, 2002;Yang et al, 2005). Recent experiments demonstrated that the major peak of broilers' PAP response to LPS cannot be attributed to 5-HT (Chapman and Wideman, 2006c;Chapman et al, 2008); therefore, in the present study we assessed the potential role of arachidonic acid (AA) derivatives such as TxA 2 .…”

“…In broilers, i.v. AA infusions trigger rapid increases the PVR and PAP without affecting the cardiac output (Wideman et al, 2005a), and the TxA 2 mimetic U44069 is an extremely potent vasoconstrictor in broilers (Wideman et al, 1999(Wideman et al, , 2005aChapman and Wideman, 2006b). Activated chicken macrophages transiently increase their production of TxA 2 (Golemboski et al, 1990).…”

Pulmonary arterial hypertension (ascites syndrome) in broilers: A review

“…Intravenous AA infusions trigger rapid increases in the pulmonary vascular resistance and pulmonary arterial pressure in broilers, and these responses are blocked by inhibiting cyclooxygenases (Wideman et al, 2005a(Wideman et al, , 2009. Thromboxane A 2 , whether administered intravenously as the TxA 2 mimetic U44069 or produced by activated thrombocytes, consistently causes pulmonary vasoconstriction and pulmonary hypertension in broilers (Wideman et al, 1996b(Wideman et al, , 1998a(Wideman et al, , 1999a(Wideman et al, , 2005a(Wideman et al, , 2009Villamor et al, 2002;Chapman and Wideman, 2006b). The precise contribution of TxA 2 to the progression of pulmonary hypertension in PAHsusceptible broilers remains to be determined.…”

Developmental changes in the effects of prostaglandin E2 in the chicken ductus arteriosus

“…Prostanoids are produced in chicken blood vessels and participate in the regulation of vascular tone (Chand and Eyre 1976;Claeys et al 1981;Wideman et al 1999). However, we have observed that in the chicken DA COX inhibitors did not produce signiWcant contractile eVects (Agren et al 2007) and did not aVect endothelium-dependent relaxation (Agren et al 2008), suggesting that locally produced PGs are not important mediators in the control of chicken ductal tone.…”