| An aqueous extract of black walnut (BW) was tested for the ability to constrict isolated equine vessels and to potentiate the concentration-response (C-R) curve for epinephrine-induced constriction of isolated equine digital vessels in the presence of hydrocortisone. Clinical signs, hematologic and serum biochemical parameters, plasma epinephrine and cortisol concentrations, distribution of digital capillary perfusion, lesions, and the efficacy of a single dose of prazosin were assessed for horses in the acute phase and in the convalescent phase of laminitis induced by an aqueous extract of BW.;Although BW failed to constrict the isolated vessels, it did reversibly potentiate the contraction of isolated equine digital vessels induced by epinephrine in the presence of hydrocortisone. All 3 of the vasodilators reversed the Epi C-R curve for the isolated equine digital vessels. Prazosin and isoxsuprine reversed the epinephrine C-R curve in a parallel fashion. Nifedipine, however, decreased the maximum height without changing the location of the epinephrine C-R curve.;All 12 horses that were dosed with BW developed acute laminitis within 8-12 hr after dosing. Affected horses became slightly stuperous and developed lower limb edema as well as clinical signs characteristic of equine laminitis. After BW dosing, a transient neutropenia developed before the onset of lameness. Mild increases in plasma epinephrine and cortisol were suggested in severely affected horses. Dorsal laminar sections obtained from severely affected horses 84 hr after BW dosing were characterized by a loss of architecture and necrosis of the tips of primary epidermal laminae. These laminae had epidermal regeneration with increased numbers of mitotic figures and disorganized clusters of epidermal cells, and a proliferative response of the dermal vasculature.;Digital and laminar perfusion were decreased relative to perfusion of the distal limb in horses with acute BW-induced laminitis. This effect was reversed using prazosin. Horses convalescing from laminitis exhibited a relative increase in dorsal laminar perfusion when compared to predose controls. Thus, quantitative models for use in vitro and in vivo were described to enable screening of potential vasoactive drugs for the treatment of relative changes in digital and laminar perfusion associated with laminitis. |
