Alpha-adrenoceptor antagonists and chemical sympathectomy exacerbate anaphylaxis-induced hypotension, but not portal hypertension, in anesthetized rats

Abstract

Anaphylactic shock is sometimes life-threatening, and it is accompanied by hepatic venoconstriction in animals, which, in part, accounts for anaphylactic hypotension. Roles of norepinephrine and α-adrenoceptor in anaphylaxis-induced hypotension and portal hypertension were investigated in anesthetized ovalbumin-sensitized Sprague-Dawley rats. The sensitized rats were randomly allocated to the following pretreatment groups ( n = 6/group): 1) control (nonpretreatment), 2) α1-adrenoceptor antagonist prazosin, 3) nonselective α-adrenoceptor antagonist phentolamine, 4) 6-hydroxydopamine-induced chemical sympathectomy, and 5) surgical hepatic sympathectomy. Anaphylactic shock was induced by an intravenous injection of the antigen. The systemic arterial pressure (SAP), central venous pressure (CVP), portal venous pressure (PVP), and portal venous blood flow (PBF) were measured, and splanchnic [Rspl: (SAP−PVP)/PBF] and portal venous [Rpv: (PVP−CVP)/PBF] resistances were determined. Separately, we measured efferent hepatic sympathetic nerve activity during anaphylaxis. In the control group, SAP markedly decreased, followed by a gradual recovery toward baseline. PVP and Rpv increased 3.2- and 23.3-fold, respectively, after antigen. Rspl decreased immediately, but only transiently, after antigen, and then increased 1.5-fold later than 10 min. The α-adrenoceptor antagonist pretreatment or chemical sympathectomy inhibited the late increase in Rspl and the SAP recovery. Pretreatment with α-adrenoceptor antagonists, or either chemical or surgical hepatic sympathectomy, did not affect the antigen-induced increase in Rpv. Hepatic sympathetic nerve activity did not significantly change after antigen. In conclusion, α-adrenoceptor antagonists and chemical sympathectomy exacerbate anaphylaxis-induced hypotension, but not portal hypertension, in anesthetized rats. Hepatic sympathetic nerves are not involved in anaphylactic portal hypertension.