How Is the NaCl signal transmitted in NaCl-induced hypertension?

Abstract

Is the NaCl signal perceived as a small increase in the concentration of NaCl in extracellular fluid? We used 8 g NaCl/100 g soluble nutrients and fed only a hypertonic (1.4% NaCl) or a hypotonic (0.45% NaCl) drink to Dahl salt-sensitive (DS) rats. After 12 weeks, 11 rats receiving the hypertonic drink had a mean blood pressure of 195 mm Hg versus 195 mm Hg in 12 rats receiving the hypotonic drink. Thus, the high-NaCl signal seems unrelated to a higher NaCl concentration in extracellular fluid, thereby suggesting volume signals. Most volume controls are near the third brain ventricle (3V). As a working hypothesis, high dietary NaCl may swell the tissues surrounding 3V, which is slitlike. Such swelling would partially close the upper part of the slit and cause ependymal cells and nerve fibers on opposite walls to touch, possibly leading to hypertension in susceptible humans or rats. To test this, we stereotaxically blocked the aqueduct with inert silicone to produce hydrocephalus of 3V in DS rats and thus prevent ependymal cells and nerve fibers from touching. After blocking or sham-blocking the aqueduct, either a 6% NaCl diet or a 0.23% NaCl diet was started. Intra-arterial blood pressure was taken after 6 weeks. A group of 28 sham-blocked rats and a group of 29 blocked rats, all fed a 0.23% low NaCl diet, had equal blood pressures averaging 130 mm Hg. Forty-six sham-blocked rats fed the 6% NaCl diet averaged 175±3.0 mm Hg blood pressure, whereas 52 blocked rats fed the 6% NaCl diet averaged 149±3.2 mm Hg blood pressure. Thus, with 6% NaCl, blood pressure rose 45 mm Hg in sham-blocked rats and only 19 mm Hg in blocked rats, a 58% reduction (p<0.001). After 12 weeks on the 6% NaCl diet, 43% of the sham-blocked rats had died compared with an 8% mortality in the blocked rats, an 82% reduction in mortality (p<0.001). Twenty-seven other DS rats fed a 6% NaCl diet for 6 weeks underwent thermal lesions of periaqueductal fibers. Their blood pressures were 8 mm Hg higher than 17 rats with sham lesions (p=NS). Thus, the aqueductal block lowered blood pressure apparently not through local injury. The key finding in this study is that an aqueduct block sufficient to produce hydrocephalus will markedly lower blood pressure and mortality rate in NaCI-fed DS rats. The mechanism involved is uncertain and may or may not be explained by our working hypothesis. © 1989 American Heart Association, Inc.