Renal Neurogenic Mediation of Intracerebroventricular Angiotensin II Hypertension in Rats Raised on High Sodium Chloride Diet

TLDR: Elevated postnatal NaCl intake enhances the pressor sensitivity of the brain to Ang II, which is dependent on intact renal nerves, and increases the hypertensive response to low-dose I.C.V.

Abstract: Chronic elevation of sodium intake may affect the sensitivity of the central nervous system to intracerebroventricular (ICV) angiotensin II (Ang II) infusion. Experiments were conducted to determine the influence of raising Sprague-Dawley rats from 2 to 3 weeks of age on low (5.0 mmol/L per kg food), normal (50 mmol/L per kg food), or high (250 mmol/L per kg food) NaCl diets on renal and cardiovascular responses to low-dose ICV Ang II infusion. At 12 weeks of age, Sprague-Dawley rats were instrumented for chronic study, including brain lateral ventricular cannulation. Artificial cerebrospinal fluid was infused (0.25 μL/min ICV) during control and recovery, whereas Ang II (20 ng/min) was infused for 5 days. During the experiment, respective sodium intakes were infused intravenously over 24 hours. In rats fed high sodium, control mean arterial pressure was 115±2 mm Hg and increased to 132±4 mm Hg by day 5 of ICV Ang II infusion. This increase in arterial pressure was associated with significant ( P <.05) decreases in sodium excretion, leading to the retention of 5.4±0.6 mmol/L total sodium over the 5 days of Ang II infusion. In rats raised on low and normal sodium intakes from weaning and in 10-week-old rats exposed to a high sodium diet for only 2 weeks, arterial pressure was not increased and sodium was not retained during ICV Ang II infusion at 20 ng/min. In rats raised on the high sodium diet, bilateral renal denervation abolished the arterial hypertension and reduced the sodium retention over 5 days of ICV Ang II infusion. Thus, chronic elevation of sodium intake increases the hypertensive response to low-dose ICV Ang II infusion, which is dependent on intact renal nerves. We conclude that elevated postnatal NaCl intake enhances the pressor sensitivity of the brain to Ang II.