Neuronal Nitric Oxide Synthase Expression within the Nucleus Tractus Solitarius of Normotensive and Spontaneously Hypertensive Rats

Abstract

The skeletal muscle exercise pressor reflex (EPR) generates increases in blood pressure and sympathetic nerve activity during exercise. The pressor and sympathetic responses to EPR stimulation are exaggerated in hypertension. The afferent arm of the EPR is composed of sensory neurons that relay information to the nucleus tractus solitarius (NTS) within the brainstem. Neuronal nitric oxide synthase (nNOS), the enzyme responsible for nitric oxide (NO) production, is present within the NTS. NTS-derived NO has been demonstrated to buffer the cardiovascular response to EPR activation. Thus, a reduction in NO, and hence its buffering capacity, could account for the exaggerated cardiovascular response to activation of the EPR in hypertension. Consistent with this concept, we have previously shown that nNOS expression is reduced in the NTS of spontaneously hypertensive rats (SHR) immediately lateral to the calamus scriptorius. However, this is only one location within the NTS. The NTS comprises a large area and nNOS expression throughout the subnuclei affects NO production. Thus, there is a need to characterize nNOS expression throughout the extent of the NTS. PURPOSE: To determine nNOS protein expression at multiple locations along the lateral nuclei of the NTS in normotensive Wistar Kyoto (WKY) and SHR animals. METHODS: Male WKY (n=12) and SHR (n=14) rats were transcardially perfused with paraformaldehyde. The brainstem was excised, blocked, and cut into sequential 35 micron sections. Sections were stained immunohistochemically for nNOS protein expression. Neurons expressing nNOS within the medial NTS from 1mm rostral to 1mm caudal of the calamus scriptorius were counted. The cells counted in three consecutive tissue slices were averaged as a representation of nNOS expression within that region of the NTS. RESULTS: Cell counts indicated that SHR had less nNOS protein expression throughout the extent of the medial NTS than WKY (p<0.001). CONCLUSIONS: It has been demonstrated that SHR have less nNOS protein at multiple points within the NTS compared to WKY. This evidence supports the concept that reductions in nNOS expression decrease NO production within the NTS thereby contributing to the EPR-mediated exaggerated cardiovascular response to exercise in hypertension. Supported by NIH HL-08842