LOCAL SECRETION OF NITRIC-OXIDE AND THE CONTROL OF MAMMARY BLOOD-FLOW

Our objective was to test the hypothesis that local production of the vasorelaxant nitric oxide could regulate mammary blood now. In four la ctating Saanen goats, the response of mammary blood flow to intraarter ial infusion of the nitric oxide donor diethylamine NONOate and the in hibitor of nitric oxide synthesis N-omega-nitro-arginine was measured. Diethylamine NONOate induced a rapid and sustained increase of mammar y blood flow in the infused gland only, suggesting a direct effect on vasculature of the mammary gland. In contrast, infusion of N-omega-nit ro-arginine decreased mammary blood flow by up to 35%, and the coinfus ion of arginine, the nitric oxide precursor, with N-omega-nitro-argini ne markedly reduced its ability to decrease mammary blood flow. The di stribution of nitric oxide synthase was investigated in cryosections o f caprine and bovine mammary tissue by histochemical staining for NADP H-diaphorase activity and by immunocytochemistry using specific antibo dies against two nitric oxide synthase isoforms. Both techniques revea led nitric oxide synthase in the vascular endothelium and secretory ep ithelium of the two species. Only antibodies against nitric oxide synt hase-III showed specific staining. These results suggest that the mamm ary gland produces and responds to nitric oxide and, further, raise th e possibility that the epithelium may control its own blood supply by secreting nitric oxide.