Dentate granule cells as a central cardioregulatory site in the rat

Dentate granule cells can be selectively destroyed by intrahippocampal injections of colchicine. This study evaluates the consequences of granule cell destruction on blood pressure regulation in the normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive rat (SHR). Bilateral destruction of dentate granule cells at 6 weeks of age produced a significant increase in blood pressure in the WKY that lasted for approximately 3 weeks, and a biphasic effect (increase then decrease) in the SHR that resulted in a significant hypotensive period that persisted for 6 weeks. Granule cell destruction at 11 weeks produced a maximal hypertension in the SHR that preceded age-matched controls by 4 weeks, but produced only a small transient increase in WKY blood pressure. Dentate granule cells are the exclusive source of prodynorphin-derived peptides in the hippocampal formation and their synthesis is regulated by glucocorticoids. Evidence suggests glucocorticoids may be involved in the regulation of blood pressure and hypertension. We determined that chronic high levels of corticosterone significantly reduced hippocampal dynorphin B levels in normotensive Sprague-Dawley rats. In addition, we confirmed that naive SHRs also contain significantly lower levels of hippocampal dynorphin B. These results suggest (i) that dentate granule cells represent a discrete neural site that may exert a tonic inhibitory influence on blood pressure, (ii) that dentate granule cells are not required for the full expression of hypertension in the SHR, and (iii) that chronic high levels of corticosterone can reduce dynorphin B levels in the dentate granule cells of normotensive rats.