Mouse Anaphylactic Hypotension Is Characterized by Initial Baroreflex Independent Renal Sympathoinhibition Followed by Sustained Renal Sympathoexcitation

Abstract

Aim: The hemodynamic response to mouse systemic anaphylaxis is characterized by an initial hypertension followed by sustained hypotension. However, the defense mechanisms of the sympathetic nervous system against this circulatory disturbance is not known. Here, we investigated the renal sympathetic nerve activity (RSNA) response to mouse systemic anaphylaxis, along with the roles of carotid sinus baroreceptor, vagal nerves and the transient receptor potential vanilloid type 1 channel (TRPV1). Methods: Male ovalbumin-sensitized C57BL/6N mice were used under pentobarbital anesthesia. RSNA, systemic arterial pressure (SAP) and heart rate (HR) were continuously measured for 60 min after the antigen injection. Results: Within 3 min after antigen injection, RSNA decreased along with a transient increase in SAP. Thereafter, RSNA showed a progressive increase during sustained hypotension. In contrast, HR continuously increased. Sinoaortic denervation, but not vagotomy, significantly attenuated the renal sympathoexcitation and tachycardia from 30 and 46 min, respectively, after antigen. The responses of RSNA, SAP and HR to anaphylaxis were not affected by pretreatment with a TRPV1 inhibitor, capsazepine, or by genetic knockout of TRPV1. Conclusion: The mouse systemic anaphylaxis causes a biphasic RSNA response with an initial baroreflex-independent decrease and secondary increase. The antigen-induced sympathoexcitation and tachycardia at the late stage are partly mediated by carotid sinus baroreceptors. Either vagal nerve or TRPV1 does not play any significant roles in the RSNA and HR responses in anesthetized mice.

Keywords: TRPV1; anaphylaxis; autonomic nerves; baroreflex; mice; vagal afferents.

Figure 1

The changes in RSNA and hemodynamic variables after antigen injection in anesthetized mice. The typical raw data of RSNA and cardiovascular responses to anaphylaxis are presented, and expanded raw data of RSNA are represented in upper area (A). Time-course data of the changes in RSNA (B), MAP (C), and HR (D) after antigen injection or treatment of PNE injection and hemorrhage in mice are also shown. ●, the sensitized mice (anaphylaxis); ○, the nonsensitized mice (control); □, mice treated with PNE injection and hemorrhage (PNE + hemorrhage); ▲, SAD mice treated with PNE injection and hemorrhage (PNE + hemorrhage, SAD). The numbers of mice used are given in parentheses. Values are expressed as means ± SD. ^#P < 0.05 vs. the nonsensitized mice (control). ^†P < 0.05 the anaphylaxis group vs. the PNE + hemorrhage group. ^*P < 0.05 vs. the baseline; the black bar, white bar and gray bar show the significant changes in anaphylaxis group, PNE + hemorrhage group, and PNE + hemorrhage + SAD group, respectively.

Figure 2

Renal sympathetic and cardiovascular responses to anaphylactic hypotension in the intact, vagotomized, and SAD mice. Summary of the changes in RSNA (A), MAP (B), and HR (C) after antigen injection in the intact mice (●), vagotomized mice (▲), and SAD mice (□). The numbers of mice used are given in parentheses. Values are expressed as means ± SD. ^#P < 0.05 vs. the intact mice. ^*P < 0.05 vs. the baseline; the black bar, white bar and gray bar show the significant changes in intact mice, SAD mice and vagotomized mice, respectively.

Figure 3

Effects of a TRPV1 blocker on renal sympathetic and cardiovascular responses to anaphylactic hypotension. Time-course data of the changes in RSNA (A), MAP (B), and HR (C) after antigen injection in the sensitized and vehicle-pretreated mice (●; vehicle anaphylaxis), the sensitized and CPZ-pretreated mice (□; CPZ anaphylaxis), the nonsensitized and vehicle-pretreated mice (▲; vehicle control), and the nonsensitized and CPZ-pretreated mice (♦; CPZ control). The numbers of mice used are given in parentheses. Values are expressed as means ± SD. ^#P < 0.05 vs. the vehicle control group; ^*P < 0.05 vs. the baseline; the black bar and white bar show the significant changes in vehicle anaphylaxis group and CPZ anaphylaxis group, respectively.

Figure 4

Renal sympathetic and hemodynamic responses to anaphylactic hypotension in TRPV1^−/− mice. Time-course data of the changes in RSNA (A), MAP (B), and HR (C) during anaphylactic shock in TRPV1−/− mice (□), and wild-type mice (●). The numbers of mice used are given in parentheses. Values are expressed as means ± SD. ^*P < 0.05 vs. the baseline; the black bar and white bar show the significant changes in wild-type mice and TRPV1^−/− mice, respectively.