Anaphylactic shock accidents after allergen exposure are frequent. After immunization with ovalbumin (OVA), a common dietary constituent, we evaluated the efficacy of pretreatment with histamine-receptor or serotonin-receptor blockers administered alone or in combination with a nitric oxide synthase inhibitor (L-NAME) on OVA-induced anaphylactic shock in Brown Norway rats. Animals were allocated to the following groups (n = 6 each): control (0.9% saline); diphenydramine (15 mg kg(-1)); cimetidine (20 mg kg(-1)); diphenydramine + cimetidine; dihydroergotamine (50 microg kg(-1)); diphenydramine + cimetidine + dihydroergotamine; L-NAME (100 mg/kg) alone or associated with diphenydramine, cimetidine, diphenydramine + cimetidine, dihydroergotamine, or diphenydramine + cimetidine + dihydroergotamine. Mean arterial blood pressure (MABP), heart rate (HR), and survival time were monitored for 60 min following treatment. The shock was initiated with i.v. OVA. The MABP drop after i.v. OVA was worsened by diphenydramine and was modestly attenuated by cimetidine, dihydroergotamine, or both together. L-NAME potentiated slightly the effects of cimetidine and dihydroergotamine by lessening the initial MABP decrease, but this transient effect was not sufficient to prevent the final collapse or to improve survival time. Decreased vasodilatory (prostaglandins E2), increased vasoconstrictory (thromboxane B2) prostaglandins, and unchanged leukotriene C4 concentrations were contributory to the overall hemodynamic changes. Thus, the combined blockade of vasodilator mediators (histamine, serotonin, and nitric oxide) slowed the MABP drop in anaphylactic shock, but did not improve survival. More studies are needed to understand these discordant effects.

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Hyponatremia is a common electrolyte abnormality that causes symptoms as a result of swelling of brain cells. We evaluated the impact of a negative balance for sodium (Na) and potassium (K) salts on the intracellular fluid (ICF) volume, emphasizing the role of anions excreted with K. Rats (N = 10) were deprived of food and water for 24 hours. They received half-isotonic saline to expand their extracellular fluid (ECF) volume by 20%; a long acting antidiuretic hormone (DDAVP) preparation was given to prevent the excretion of electrolyte-free water. The concentration of Na in plasma fell from 139 +/- 1 mM to 120 +/- 2 mM 24 hours after the infusion of hypotonic saline (P < 0.01). Since these rats had a small negative balance for water (4 +/- 1 ml), hyponatremia was due to their negative balances for Na (2.2 +/- 0.3 mmol) and K (2.2 +/- 0.1). There were negative balances for Cl (2.4 +/- 0.2 mmol) and phosphate (0.7 +/- 0.05 mmol). Despite the negative balance for NaCl, the ECF volume as assessed by 3H-inulin space was not contracted. In this model for acute hyponatremia, its basis was electrolyte loss, but the ECF volume was not contracted, suggesting that water shifted from the ICF to the ECF. Hyponatremia is associated with cell swelling only if its cause is positive water balance and/or is loss of Na from the ECF. It is critical to examine the urine anions to determine the compartment of origin of particles excreted with K and thereby whether hyponatremia will result in overall expansion or contraction of the ICF volume.

Recent findings in human septic shock suggest that glucocorticosteroids can limit and even reverse hemodynamic disturbances and dependence on catecholamines. In a rodent model of hypotensive and hypokinetic septic shock, we investigated the effects of early or late dexamethasone administration on hemodynamics, response to catecholamines, and cardiac beta-adrenergic signalling. As compared with sham-operated rats, the untreated septic rats displayed significant arterial hypotension and reduced aortic blood flow. However, in vivo pressor response to epinephrine and phenylephrine was not different among sham and septic animals. Conversely, the chronotropic response to isoproterenol was significantly attenuated in septic animals. Steroid-treated septic animals displayed complete reversal of hypotension, improvement in aortic blood flow, and reduced plasma lactate and nitrite/nitrate concentrations as compared with untreated septic animals. The number of myocardial beta-adrenergic receptors and in vivo isoproterenol-stimulated myocardial cAMP content were similar in sham and septic animals. Glucocorticosteroids, although not changing these patterns, significantly decreased the receptors affinity when administered late, but not early. In this model of septic shock, hemodynamic abnormalities may not be related to adrenergic receptor desensitization. That steroids can improve them suggests that they could act mainly distal to adrenergic receptors, for instance, on myocardial and vascular smooth fiber contraction properties through mechanisms probably including inducible nitric oxide synthase inhibition.