This project will study the role of the neuropeptide substance P in CNS regulation of blood pressure and possible abnormalities of this system in hypertension. This project comprises 4 Areas, with the following specific aims: Area I: Conduct studies in normal and spontaneously hypertensive rats on effects of administration into the fourth ventricle and into the nucleus tractus solitarius of peptides related to Substance P, of enzymes which process Substance P and of antisera directed against these enzymes. Area II: Isolate, purify and characterize the enzymes which process Substance P in rat brain. Area III: Raise monoclonal and polyclonal antibodies directed against the enzymes which process Substance P in rat brain. Area IV: Conduct immunocytochemical studies to localize the Substance P-processing enzymes at the light and electron microscopic level in the CNS of normal and hypertensive rats. To develop methods to measure the enzymes. Substance P appears to be an essential neurotransmitter for regulation of blood pressure, both at afferent and efferent levels. Substance P appears to exert its neurotransmitter and/or neuromodulator effects in the CNS only after processing by enzymes which produce N-terminal or C-terminal fragments. These enzymes will be characterized, localized and quantitated in normal and spontaneously hypertensive rats.
