Abstract 1601: Acute Elevations in Plasma Osmolality Lead to Sympathetic Activation in Humans
Background: Recent data in experimental animals suggest that increases in plasma sodium concentration activate centrally located osmoreceptors which trigger sympatho-excitation. This sympatho-excitation may be one of the mechanisms underlying salt sensitive hypertension. We examined this issue in humans.
Hypothesis: We hypothesized that an osmotic stimulus designed to acutely increase plasma osmolality would lead to sympatho-excitation.
Methods: To test this hypothesis, 47 normotensive adults (24±1 yrs) underwent a 60-min intravenous infusion of hypertonic saline (3% NaCl; HSI); 13 of these subjects also completed a control trial of isotonic saline (0.9% NaCl; ISO) on a different day. The infusion rate was 0.15 ml/kg/min (range: 477–904 mL). We assessed plasma osmolality (osmometer), sodium concentration (ion selective electrode), hematocrit (microcentrifuge), heart rate (ECG), and beat-by-beat blood pressure (BP; finometer). Our index of sympathetic activity was circulating norepinephrine (NE; HPLC).
Results: The HSI provided an effective osmotic stimulus, increasing plasma osmolality from 288±0.5 to 297±0.5 mOsm/kg (p<0.05) and sodium concentration from 135.1±0.4 to 140.5±0.3 mmol/L (p<0.05); there was no change in osmolality (289±1.0 to 289±0.9 mOsm/kg; p<0.40) or sodium concentration (136.5±0.7 to 136.8±0.5 mmol/L; p<0.40) during the ISO infusion. Hematocrit declined more in the HSI trial than in the ISO trial (p<0.05). Heart rate increased during the HSI (p<0.05) but not the ISO trial. Mean BP increased more during the HSI compared to the ISO (p<0.05). NE increased 27±6%, from 216±13 to 265±18 pg/ml during the HSI (p<0.05). There was no change in NE during the ISO trial (173_20 to 178±28; p<0.40). There was a modest correlation between the change in NE and BP during the HSI (r=0.30, p<0.05).
Conclusion: These data lend support to the hypothesis that elevated plasma osmolality triggers sympatho-excitation, which is consistent with mechanistic studies performed in experimental animals. In conclusion, acute increases in plasma osmolality lead to increases in NE in humans.