The NK, Receptor Antagonist GR-82334 in the NTS Attenuates the Muscle Pressor Response

The present study on chloralose anesthetized cats (n=18, 2.7±0.1 kg) was designed to determine what role substance P (SP) plays in mediating the muscle presser response in the CNS. SPantibody coated probes (Williams, et al. Neuropeptides 26: 319327; 1994) were placed in the rostral brainstem during rest and isometric contraction [1C] (n=4) and indicated that immunoreactive SP (irSP) was released from the medial nucleus of the solitary tract (mNTS) during 1C. During the 1C with no injections into the CNS, the BP increased 60±12 mm Hg above rest (n=15,p\u3c0.01). To determine what role SP may play in this area, the NK1 specific antagonist GR-82334 (50pmol/50nl) was injected bilaterally into the mNTS. After bilateral 50nl vehicle injections of 0.9% saline (n=4), BP increased 52±13mm Hg above rest during IC (p\u3c0.03), but only increased 4±7mm Hg after antagonist injection (n=4, p=0.56). GR-82334 injections did not significantly alter the resting BP (n=6, p=0.94). These data indicate that irSP is released from the mNTS during fatiguing isometric contractions. They also suggest that SP is involved in the muscle presser response and that its effects in the mNTS are mediated by the NK1 receptor