Central Nervous System Gαi2-Subunit Proteins Maintain Salt Resistance via a Renal Nerve–Dependent Sympathoinhibitory PathwayNovelty and Significance
In salt-resistant phenotypes, chronic elevated dietary sodium intake evokes suppression of renal sodium-retaining mechanisms to maintain sodium homeostasis and normotension. We have recently shown that brain Gαi2 protein pathways are required to suppress renal sympathetic nerve activity and facilitate maximal sodium excretion during acute intravenous volume expansion in Sprague-Dawley rats. Here, we studied the role of brain Gαi2 proteins in the endogenous central neural mechanisms acting to maintain fluid and electrolyte homeostasis and normotension during a chronic elevation in dietary salt intake. Naive or bilaterally renal denervated adult male Sprague-Dawley rats were randomly assigned to receive an intracerebroventricular scrambled or Gαi2 oligodeoxynucleotide infusion and then subjected to either a normal salt (0.4%) or high-salt (8.0%) diet for 21 days. In scrambled oligodeoxynucleotide-infused rats, salt loading, which did not alter blood pressure, evoked a site-specific increase in hypothalamic paraventricular nucleus Gαi2 protein levels and suppression of circulating norepinephrine content and plasma renin activity. In salt-loaded rats continuously infused intracerebroventricularly with a Gαi2 oligodeoxynucleotide, animals exhibited sodium and water retention, elevated plasma norepinephrine levels, and hypertension, despite suppression of plasma renin activity. Furthermore, in salt-loaded bilaterally renal denervated rats, Gαi2 oligodeoxynucleotide infusion failed to evoke salt-sensitive hypertension. Therefore, in salt-resistant rats subjected to a chronic high-salt diet, brain Gαi2 proteins are required to inhibit central sympathetic outflow to the kidneys and maintain sodium balance and normotension. In conclusion, these data demonstrate a central role of endogenous brain, likely paraventricular nucleus-specific, Gαi2-subunit protein–gated signal transduction pathways in maintaining a salt-resistant phenotype.
- blood pressure regulation
- central G-protein–coupled receptors
- renal sympathetic nerves
- sympathetic nervous system
- salt-sensitive hypertension
- Received August 14, 2012.
- Revision received October 31, 2012.
- Accepted November 9, 2012.
- © 2013 American Heart Association, Inc.