Mechanisms Involved in Sodium Depletion-Induced Facilitation of Respiratory Responses to Baroreceptor Activation

Disorders in blood volume may cause behavioral, hormonal and autonomic responses in order to restore homeostasis. The model of sodium depletion elicited by furosemide promotes neuroendocrine responses, reductions in vascular reactivity and blood volume, with no changes in blood pressure and heart rate (HR) due to the activation of the renin‐angiotensin system. It was demonstrated that changes in the sodium balance modifies the cardiorespiratory responses to peripheral baroreceptor activation in anesthetized conditions. In the present study, we explored the cardiorespiratory baroreflex responses in normovolemic and 24‐h sodium depleted conscious rats and evaluated the contribution the angiotensinergic mechanisms in the reflex responses of both groups. Male Holtzman rats (290–320 g, n=19/group) that received catheter implants into the femoral artery and vein were used. Baroreceptor activation was performed by intravenous (iv) phenylephrine (phenyl) infusions (5 μg/kg/ml) and ventilation (VE) was measured by whole body plethysmograph. Subcutaneous furosemide injections (20 mg/kg) followed by 24 h of sodium‐deficient diet was used to induce sodium depletion. Sodium‐depleted animals (n=19) showed similar baseline mean arterial pressure (102±2 vs 107±2 mmHg), HR (382±9 vs 385±7 bpm) and VE (468±27 vs 447±26 ml/min/kg) compared to normovolemic control animals (n=19). Phenyl infusions in normovolemic and sodium‐depleted rats produced similar pressor (Δ = 58±2 and 59±2 mmHg) and bradicardic (Δ = −97±10 and −120±11 bpm) responses. However, a larger increase in VE during baroreflex activation was observed in sodium‐depleted animals in comparison to controls (Δ = 152±40 vs 53±26 ml/min/kg, p<0.05). This increased VE response of sodium‐depleted rats was attenuated (Δ = 77±33 ml/min/kg) after the systemic antagonism of angiotensin II type 1 receptor with losartan (10 mg/kg). The results suggest that neuroendocrine changes produced by sodium depletion, mainly the increase in angiotensin II levels, facilitate the respiratory response to baroreceptor activation in conscious sodium‐depleted rats. Support or Funding Information FAPESP, FAPESP/Pronex, CNPq, Prope UNESP