Among the many possible mediators of the early asthmatic response, prostaglandin D2, a bronchoconstrictor, is the principal cyclooxygenase metabolite of arachidonic acid that is released upon the activation of mast cells and is also synthesized by human alveolar macrophages. We performed bronchoalveolar lavage in five patients with chronic stable asthma, before and up to nine minutes after local provocative challenge with Dermatophagoides pteronyssinus. The lavage fluid was analyzed for products of arachidonic acid metabolism. Prostaglandin D2 levels in all five patients rose an average of 150-fold, from less than 8 to 332 +/- 114 pg per milliliter (mean +/- SEM; P less than 0.050), after local instillation of the antigen. Levels of 15-hydroxyeicosatetraenoic acid, which may also have a role in the pulmonary allergic response, were detectable in lavage fluid before challenge and increased after provocation with the antigen in four of the five patients. The activity of beta-glucuronidase, an enzyme released by macrophages and mast cells upon stimulation, tended to increase in the lavage fluid after provocation in all patients. These studies provide evidence that the release of prostaglandin D2 into the airways is an early event after the instillation of D. pteronyssinus in patients who are sensitive to this antigen.

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Potassium is a major regulator of aldosterone production. It also increases adrenal renin. The causal relationship between potassium and adrenal renin is not known. To evaluate the role of the intraadrenal renin-angiotensin (ANG) system in potassium-stimulated aldosterone synthesis and release, specific adrenal renin activity, PRA, and plasma aldosterone were measured during potassium loading or captopril treatment in the rat. Adrenal ANGs were determined using a HPLC system combined with RIA to obtain quantitative information on the components of the adrenal renin-ANG system. In addition, the effect of pretreatment with captopril on aldosterone production by isolated adrenal glomerulosa cells was examined. In intact animals potassium loading markedly increased adrenal renin and plasma aldosterone, whereas PRA was suppressed. The administration of captopril to rats in normal potassium balance did not suppress plasma aldosterone. Captopril treatment during potassium loading inhibited the potassium-induced increase in aldosterone. Furthermore, pretreatment with captopril suppressed adrenal ANG II and reduced the response of aldosterone production to extracellular potassium concentration by isolated adrenal glomerulosa cells in vitro. These results suggest that the adrenal renin-ANG system plays a significant role in the control of aldosterone production under potassium stimulation.

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