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 flow. In four lactating Saanen goats, the response of mammary blood flow to intraarterial infusion of the nitric oxide donor diethylamine NONOate and the inhibitor of nitric oxide synthesis N omega-nitro-arginine was measured. Diethylamine NONOate induced a rapid and sustained increase of mammary blood flow in the infused gland only, suggesting a direct effect on vasculature of the mammary gland. In contrast, infusion of N omega-nitro-arginine decreased mammary blood flow by up to 35%, and the coinfusion of arginine, the nitric oxide precursor, with N omega-nitro-arginine markedly reduced its ability to decrease mammary blood flow. The distribution of nitric oxide synthase was investigated in cryosections of caprine and bovine mammary tissue by histochemical staining for NADPH-diaphorase activity and by immunocytochemistry using specific antibodies against two nitric oxide synthase isoforms. Both techniques revealed nitric oxide synthase in the vascular endothelium and secretory epithelium of the two species. Only antibodies against nitric oxide synthase-III showed specific staining. These results suggest that the mammary gland produces and responds to nitric oxide and, further, raise the possibility that the epithelium may control its own blood supply by secreting nitric oxide.