Orthostatic hypotension (OH) can cause syncope that is difficult to treat. We have found that 473 mL (16 oz) of water can increase systolic blood pressure (SBP) by > 30 mm Hg in many OH patients (the gastropressor response). OH patients are routinely advised to increase their sodium intake to augment their blood volume. We tested the hypothesis that the ingestion of salt with water would increase the magnitude of the acute pressor response compared with water alone in patients with OH. Patients with OH (n = 9; female = 5; 65+/-3 years) underwent a randomized crossover trial of drinking water (H2O) and salt water (NaCl-H2O). Noninvasive heart rate and BP were measured with the patient seated for > or = 60 minutes after ingestion. The area under the curve for SBP was greater with H2O than NaCl-H2O for the 30 minutes (714+/-388 mm Hg x min versus 364+/-369 mm Hg x min; P = 0.002) and 60 minutes (1454+/-827 mm Hg x min versus 812+/-734 mm Hg x min; P = 0.048) after ingestion. The increase in SBP with H2O was greater than with NaCl-H2O at 30 minutes (37+/-6 versus 18+/-5 mm Hg; P = 0.006) but not at 60 minutes (17+/-6 versus 10+/-6 mm Hg; P = 0.4). Norepinephrine increased after H2O (P = 0.018) but not after NaCl-H2O (P = 0.195). Both oral water and salt water increase BP in patients with OH. Instead of augmenting the gastropressor response, the additional salt paradoxically attenuates the pressor response to water. These data suggest a potentially important role for gastrointestinal osmolality in the activation of the sympathetic nervous system leading to cardiovascular reflexes responsible for the gastropressor response.