Central infusions of
benzamil prevent/reverse
salt-induced
hypertension in genetic models of
salt-sensitive
hypertension.
Benzamil acts by blockade of ion--presumably
sodium--channels. In the present study, we assessed in Dahl
salt-sensitive (S) rats on high
salt intake whether these channels mediate increases in brain "
ouabain" and, thereby,
hypertension. Intracerebroventricular (icv) infusions of a low (1.2 microg/kg per hour) or high (4.0 microg/kg per hour) dose of
benzamil were given to Dahl S rats on high
salt diet (1370 micromol Na+/g food) for 2 or 4 weeks. "
Ouabain" content was measured using a specific
enzyme-linked
immunosorbent assay (ELISA). Systolic blood pressure (BP) in Dahl S rats on high
salt for 4 weeks increased markedly (188+/-10 versus 128+/-4 mm Hg, n=8, P<0.05).
Benzamil fully blocked this increase (131+/-7 mm Hg after the high dose of
benzamil). Hypothalamic and pituitary "
ouabain" increased significantly (22+/-7 versus 12+/-3 and 151+/-38 versus 69+/-6 ng/g tissue, respectively, P<0.05) in Dahl S rats on high
salt versus regular
salt diet for 2 weeks.
Benzamil blocked these increases of brain "
ouabain" to high
salt intake. Similarly, high
salt intake for 4 weeks increased hypothalamic (18+/-2 versus 13+/-1 ng/g tissue, P<0.05) and pituitary (183+/-30 versus 78+/-8 ng/g tissue, P<0.05) "
ouabain."
Benzamil also inhibited these increases of brain "
ouabain." Both hypothalamic and pituitary "
ouabain" showed significant positive correlations with BP. In contrast, high
salt intake did not affect "
ouabain" levels in the adrenal gland or plasma in Dahl S rats on high
salt for either 2 or 4 weeks. These findings indicate that in Dahl S rats high
salt intake only increases brain and not peripheral "
ouabain" and that
benzamil-blockable brain
sodium channels mediate the increases in brain "
ouabain" and the subsequent
hypertension.