Differential effects of cyclooxygenase inhibitors on the cardiovascular response to hyperosmotic mannitol

The intravenous infusion of mannitol (1.37 mosm kg-1 min-1 during 4 min) to anesthetized, open-chest, intact dogs produced a hemodynamic response characterized by a positive inotropic effect and a decrease in total peripheral resistance. This response is attributable to a direct effect of hypertonicity (plasma osmolality raised from 309 +/- 4 to 332 +/- 5 mosm kg-1 H2O). Pretreatment with indomethacin (5 mg kg-1 i.v.) or meclofenamic acid (2 mg kg-1 i.v.) attenuated the mannitol-induced response but acetylsalycilic acid (10 mg kg-1 i.v.) was without effect. Indomethacin (5 mg kg-1 i.v.) did not change the decrease in canine hindlimb perfusion pressure produced by intra-arterial mannitol 5 mosm kg-1. Indomethacin (3 microM) did not alter the chronotropic and inotropic responses to mannitol (150 mosm above normal) in isolated rabbit atria. These results suggest that the cardiovascular response to hyperosmotic mannitol may be partly mediated in intact animals by prostaglandin release.