Involvement of splanchnic vascular bed in anaphylactic hypotension in anesthetized BALB/c mice

Abstract

August 22, 2007; doi:10.1152/ajpregu.00904.2006.-Using in vivo and isolated perfused liver preparations of BALB/c mice, we determined the roles of the liver and splanchnic vascular bed in anaphylactic hypotension. Intravenous injection of ovalbumin antigen into intact-sensitized mice decreased systemic arterial pressure (Psa) from 92 Ϯ 2 to 39 Ϯ 3 (SE) mmHg but only slightly increased portal venous pressure (Ppv) from 6.4 Ϯ 0.1 cmH2O to the peak of 9.9 Ϯ 0.5 cmH2O at 3.5 min after antigen. Elimination of the splanchnic vascular beds by ligation of the celiac and mesenteric arteries, combined with total hepatectomy, attenuated anaphylactic hypotension. Ligation of these arteries alone, but not partial hepatectomy (70%), similarly attenuated anaphylactic hypotension. In contrast, isolated sensitized mouse liver perfused portally at constant flow did not show anaphylactic venoconstriction but, rather, substantial constriction in response to the anaphylaxisassociated platelet-activating factor, indicating that venoconstriction in mice in vivo may be induced by mediators released from extrahepatic tissues. These results suggest that splanchnic vascular beds are involved in BALB/c mouse anaphylactic hypotension. They presumably act as sources of chemical mediators to cause the anaphylaxisinduced portal hypertension, which induced splanchnic congestion, resulting in a decrease in circulating blood volume and, thus, systemic arterial hypotension. Mouse hepatic anaphylactic venoconstriction may be induced by factors outside the liver, but not by anaphylactic reaction within the liver. anaphylactic shock; hepatic circulation; portal hypertension; splanchnic congestion ANAPHYLACTIC HYPOTENSION appears to be caused primarily by a decrease in blood flow to the heart, because left ventricular function is relatively well preserved during anaphylactic shock (1, 2). Peripheral circulatory collapse is ascribed to hypovolemia, which results from a decrease in effective circulating blood volume. The latter could be due to vasodilation with the peripheral pooling and increased vascular permeability with a shift of intravascular fluid to the extravascular space (1, 2).In canine experimental models of anaphylactic shock, an increase in resistance to venous return is important in the pathogenesis of circulatory collapse (27): increased venous resistance decreases venous return, with a resultant decrease in stroke volume and systemic arterial pressure. Indeed, eviscerated dogs did not develop anaphylactic shock (19). In addition, Enjeti et al. (9) reported that the severity of the anaphylactic shock could be decreased by occlusion of the descending aorta. In dogs, the anaphylaxis-induced increase in venous resistance is partly caused by constriction of the hepatic veins (27, 30), which induces pooling of blood in the liver, as well as in upstream splanchnic organs. In addition, we recently demonstrated that the liver and splanchnic vascular beds are involved in rat anaphylactic hypotension by showing that elimination of splanchnic ci...

PAF, rather than Histamine, Participates in Mouse Anaphylactic Hypotension

“…We have proposed that the liver and splanchnic vascular beds are involved in anaphylactic hypotension [6][7][8] and recently confirmed their importance in the pathogenesis of mouse anaphylactic hypotension [8] . Thus, us- ing a PAF receptor antagonist, CV-6209, and a nonspecific histamine H 1 receptor antagonist, diphenhydramine (DPH), we determined the roles of PAF and histamine in both systemic and hepatic circulation during anaphylactic hypotension in anesthetized BALB/c mice.…”

“…The mice were actively sensitized by the subcutaneous injection of an emulsion made by mixing aluminum potassium sulfate adjuvant (2 mg) with 0.01 mg ovalbumin (grade V, Sigma) dissolved in physiological saline (0.2 ml) [8] . The antigen emulsion was injected again 1 week after the first antigen injection.…”

NG-Nitro-L-arginine Methyl Ester, but Not Methylene Blue, Attenuates Anaphylactic Hypotension in Anesthetized Mice

“…Indeed, elimination of the liver and splanchnic circulation by total hepatectomy combined with ligation of the celiac and mesenteric arteries attenuates anaphylactic hypotension in anesthetized rats (5). More recently, the same surgical procedures (hepatectomy and elimination of the splanchnic vascular bed) have been shown to attenuate mouse anaphylactic hypotension (6). However, in the present study, antigen-induced increases in Ppv were observed in both L-NAME and D-NAME groups, although a significantly smaller decrease in Psa after antigen occurred in the L-NAME group compared to the D-NAME group.…”

“…In addition, in sensitized rabbits, anaphylactic hypotension is accompanied by substantial portal hypertension (4), although right heart overload due to pulmonary hypertension is recognized as a causative factor (8). In rats, antigen-induced hepatic venoconstriction also contributes to anaphylactic hypotension (5), and we have recently reported that the liver and splanchnic vascular beds are also involved in mouse anaphylactic hypotension (6).…”

The responses of the hepatic and splanchnic vascular beds to vasopressin in rats

“…Following a midline incision of the abdominal wall, a catheter (ID 0.47 mm, OD 0.67 mm) was inserted directly into the main portal vein. This catheter was connected to a Y-type miniature plastic tube (7,24), one twig end of which was connected via a water-filled polyethylene tube to the pressure transducer for measurement of Ppv, and another twig end was used to introduce a thin inner polyethylene tube, which was tapered to ~0.3 mm in diameter over hot air, for an intravenous injection of vasopressin. The total hepatic blood flow (HBF) was measured with an ultrasound transit-time flow probe (Transonics, Ithaca, NY), which was 2 mm in width, and placed around both the portal vein and the hepatic artery at the hepatic hilum.…”