Pulmonary Vasoconstrictive and Bronchoconstrictive Responses to Anaphylaxis Are Weakened via β2-adrenoceptor Activation by Endogenous Epinephrine in Anesthetized Rats

Abstract

Background: Patients treated with propranolol, a nonselective ␤-adrenoceptor antagonist, have increased incidence and severity of anaphylaxis. We determined whether ␤ 1 -or ␤ 2 -adrenoceptor antagonist modulated pulmonary vasoconstriction and bronchoconstriction in rat anaphylactic hypotension. Methods: Anesthetized ovalbumin-sensitized male SpragueDawley rats were randomly allocated to the following pretreatment groups (n ϭ 7/group): (1) sensitized control (nonpretreatment), (2) propranolol, (3) the selective ␤ 2 -adrenoceptor antagonist ICI 118,551, (4) the selective ␤ 1 -adrenoceptor antagonist atenolol, and (5) adrenalectomy. Shock was induced by an intravenous injection of the antigen. Mean arterial pressure, pulmonary arterial pressure, left atrial pressure, central venous pressure, portal venous pressure, airway pressure, and aortic blood flow were continuously measured. Results: In either sensitized control or atenolol-pretreated rats, mean arterial pressure and aortic blood flow decreased substantially, whereas pulmonary arterial pressure and airway pressure did not increase soon after antigen injection. In contrast, in rats pretreated with either propranolol, ICI 118,551, or adrenalectomy, airway pressure significantly increased by 14 cm H 2 O, and pulmonary arterial pressure by

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

“…This finding contrasts with the results of our previous studies using the same anaphylaxis rat models (32,33), in which all rats pretreated with the ␤ 2 -adrenoceptor antagonists ICI118,551 or propranolol, died within 50 min after antigen; 40% of those pretreated with the ␤ 1 -adrenoceptor antagonist atenolol died within 60 min. These results suggest that the detrimental action of ␣-adrenoceptor inhibition is less than that of ␤-adrenoceptor inhibition in anaphylactic hypotension.…”

“…after antigen (32). Thus, we suppose that the circulating norepinephrine released from organs other than liver may contribute to constriction of the hepatic vessels, even if hepatic sympathetic nerve activity does not increase.…”

“…One explanation is that the circulating levels of epinephrine, which could dilate hepatic vessels via ␤-adrenoceptors (10, 25) increased much more than that of norepinephrine (32), counteracting the vasoconstrictor action of norepinephrine. However, this seems unlikely because ␤-adrenoceptor blockade did not affect the anaphylaxis-induced increases in PVP of anesthetized rats (32,33). Here, for the first time, we demonstrated that hepatic sympathetic nerve activity did not increase, but tended to decrease, in response to anaphylactic hypotension.…”

“…from the sympathetic nerve terminals in anaphylactic shock have not been determined, although those of ␤-adrenoceptors and epinephrine released from the adrenal gland have been reported (32). It remains unknown whether the peripherally released norepinephrine exerts beneficial actions against anaphylactic shock; the effects on anaphylaxis of the norepinephrine-selective neurotoxic drug 6-hydroxydopamine (6-OHDA), which destroys peripheral norepinephrine terminals (8,18), have not been examined in animal models.…”

“…As an alternative mechanism, activation of the sympathetic nervous system may evoke anaphylactic hepatic venoconstriction; electrical stimulation of the rat hepatic sympathetic nerve induced constriction of the hepatic vessel (3,9). In addition, circulating norepinephrine increases during systemic anaphylaxis (32) and may constrict hepatic vessels via activation of ␣-adrenoceptors (22). However, the response of the hepatic sympathetic nerve activity to anaphylactic hypotension or its role in anaphylactic portal hypertension remains unknown.…”