Angiotensin II and vasopressin are involved in the defense system against anaphylactic hypotension in anesthetized rats

Abstract

Anaphylactic shock is sometimes life-threatening, but the defense system against this circulatory failure was not fully understood. Ameliorating roles of angiotensin (ANG) II and vasopressin in anaphylactic hypotension were investigated in anesthetized ovalbumin-sensitized Sprague-Dawley rats. The sensitized rats were randomly allocated to the following pretreatment groups (n=7/group): (1) control (non-pretreatment), (2) ANG II synthesis inhibitor captopril, (3) ANG II receptor antagonist losartan, and (4) V1a vasopressin receptor antagonist. 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 vascular resistance (Rspl: (SAP-PVP)/PBF) was determined. In the control group, SAP markedly decreased, followed by a gradual recovery toward baseline. Rspl transiently decreased immediately after antigen, and then increased 1.5-fold at 15 min and thereafter. The pretreatment with either losartan, captopril or V1a receptor antagonist augmented the initial fall of SAP and attenuated the SAP recovery along with augmentation of the late increase in Rspl. The 2-h survival rate was significantly smaller in either pretreatment group than in the control group (100%). Plasma levels of ANG II and vasopressin increased to 3.8- and 9.8-fold, respectively, at 30 min after antigen in the control group, whereas captopril pretreatment inhibited the increase in ANG II. In conclusion, inhibition of ANG II or vasopressin exacerbates anaphylaxis-induced hypotension in anesthetized rats.

Introduction

Anaphylactic shock is a serious allergic reaction and is potentially life threatening (Brown, 1995). The knowledge on the defense system against hemorrhagic shock is well established: profound hemorrhage activates a number of compensatory mechanisms, including activation of the sympathetic nervous system and release of circulating vasoconstrictor hormones such as vasopressin and angiotensin (ANG) II, which act synergistically to achieve the subsequent cardiovascular recovery (Ponchon and Elghozi, 1997). In contrast, the defense system against anaphylactic shock is not well known. We have recently shown using the rat anaphylactic shock model that activation of the sympathetic nervous system is crucial against anaphylactic shock: β-adrenergic receptor activation is necessary to prevent early fatal outcome (Zhang et al., 2011a, Zhang et al., 2011b); norepinephrine released from the sympathetic nerve endings and α-adrenergic receptor activation exerted beneficial effects at the recovery phase (Wang et al., 2013) in anesthetized rats suffering from anaphylactic shock. However, the roles of other compensatory vasoconstrictor hormones such as vasopressin and ANG II in anaphylactic shock remain unknown. The patients administered of angiotensin converting enzyme synthesis inhibitors or its receptor antagonists show increased severity of anaphylactic shock (Sampson et al., 2005), suggesting the ameliorating action of ANG II against anaphylactic hypotension.

The purpose of this study was to determine the roles of ANG II and vasopressin in the compensatory defense system against anaphylactic shock. We studied the effects of pharmacological inhibition of ANG II and vasopressin on anaphylactic hypotension in anesthetized rats.