Nitric oxide and salt sensitivity.

Studies in laboratory animals suggest that altered nitric oxide (NO) production may be associated with salt sensitivity. In this investigation we determined whether the endogenous NO production was altered in salt-sensitive human subjects when salt intake was changed. Salt sensitivity was assessed from the magnitude of the blood pressure (BP) lowering obtained when the salt intake was reduced from high to a low intake. The combined urinary excretion of nitrites and nitrates, the major metabolites of NO, was employed as an index of endogenous NO production. Salt-sensitive subjects (n = 23) were older, heavier, and had greater waist-to-hip ratios and higher baseline BP than salt-resistant individuals (n = 25). In salt-sensitive subjects, mean blood pressure (MBP) decreased 11.8+/-0.7 mm Hg, and NO metabolite excretion increased from 823+/-102 to 1530+/-148 mmol/24 h, when salt intake was reduced from 316 to 28 micromol/day. NO metabolite excretion was 45% lower during high salt (0.66+/-0.1 micromol/mg creatinine) than during low salt intake (1.12+/-0.1 micromol/mg creatinine) (P < .001). In contrast, when salt intake was reduced, salt-resistant subjects exhibited no significant mean changes in BP or NO metabolite excretion. During low salt intake, NO metabolite excretion (micromol/ day) was significantly higher in salt-sensitive individuals. The magnitude of decrease of systolic blood pressure, diastolic blood pressure, or MBP induced by reducing salt intake was not related to the increase in urinary excretion of NO metabolite levels (r2 = 0.009; P = .66). In summary, to the extent that urinary NO metabolite levels reflect the activity of the endogenous NO system, our results support the view that salt sensitivity may in part be determined by an inability to increase or to sustain NO production in response to high salt. Insufficient NO production during high salt may in turn lead to altered pressure-natriuresis relationships and to an increase in BP. The possibility that the increase in BP induced by high salt intake in salt-sensitive individuals could be the key factor in reducing NO metabolite levels can not be ruled out.

Insulin and blood pressure responses to changes in salt intake.

In this study we evaluated the role of insulin in hypertension and on salt sensitivity. The study was conducted in 47 consecutive patients attending the Center for the Detection and Treatment of Cardiovascular and Metabolic Risk factors. The relationships between fasting and post-glucose load insulin levels and the blood pressure (BP) responses to changes in salt intake, were investigated. No correlation was observed between fasting or 2-h post-load insulin levels and mean BP (MBP), systolic BP (SBP) or diastolic BP (DBP). The plasma concentrations of insulin were not significantly related to body mass index (BMI) (r2 = 0.05; P = 0.135). Neither fasting nor 2-h post-load insulin predicted the BP response to changes in salt intake. A reduction in salt intake from 316 +/- 13 to 26 PM 3 mmoles/day, produced similar BP lowering in subjects with fasting insulin >15 microU/ml and in subjects with normal fasting insulin levels (<15 microU/ml). In addition, no relationship was observed between the magnitude of the BP responses to salt and the levels of insulin, either fasting (r2 = 0.007; P = 0.86) or 2-h after a glucose load (r2 = 0.01; P = 0.213). A very strong association was found between body weight or BMI and MBP (r2 = 0.443; P< 0.0001). In conclusion, our results are against the view of a cause-effect relationship between insulin and BP levels. In addition, the insulin status of a patient does not predict (nor determines) his (her) vascular reactivity to changes in salt intake. Finally, our findings further support the existence of a strong and direct association between body weight and hypertension, and speak against a major role of insulin in the pathogenesis of hypertension associated with obesity.