Fumihiro Miura

Renal sodium handling and sodium transport inhibitor in salt-sensitive essential hypertension.

To investigate the mechanism whereby blood pressure rises with NaCl loading in salt-sensitive essential hypertension, salt-sensitivity index was determined along with sodium and lithium clearances, plasma Na+, K+-ATPase inhibitor and intra-erythrocyte sodium and potassium concentrations. Salt-sensitivity index was defined as the percentage of change in mean blood pressure when NaCl intake was changed from low (34 mmol/day) to high (342 mmol/day). Salt-sensitivity index was inversely correlated with fractional excretion of lithium both on the low and high NaCl diets (r = −0.721, P < 0.01 and r = −0.591, P < 0.02, respectively; n = 16), but not with fractional excretion of sodium. The change of plasma Na+, K+-ATPase inhibition with NaCl loading had a direct correlation with salt-sensitivity index (r = 0.704, P < 0.01; n = 16). Either intra-erythrocyte sodium and potassium concentrations or the ratio of these two values did not change significantly with an increase of dietary NaCl intake. These results suggest that an enhancement of proximal tubular sodium reabsorption stimulates secretion of plasma Na+, K+-ATPase inhibitor which may be involved in a rise in blood pressure with sodium loading. They also suggest that lithium clearance is a determinant which can predict salt sensitivity without actual NaCl loading.

Is salt sensitivity in essential hypertension affected by ageing

To investigate the question of whether the salt sensitivity of blood pressure in human essential hypertension is affected by ageing, the salt-sensitivity index was determined in 54 hospitalized patients with essential hypertension, aged 26–67 years (mean ± s.d. 46.9 ± 9.5 years) as well as plasma inhibition of Na+, K+-ATPase (sodium-pump inhibitor), erythrocyte sodium and potassium concentrations and fractional excretion of lithium. The salt-sensitivity index was calculated as the percentage change in mean blood pressure when the dietary sodium content was increased from 34 mmol/day (low sodium) to 340 mmol/day (high sodium) for 8 days each. Despite wide range of ages, age showed no correlation with the salt-sensitivity index, the sodium-pump inhibitor, the erythrocyte Na+: K+ ratio or fractional excretion of lithium. Furthermore, the distribution of the salt-sensitivity index did not differ between older (45 years old) and younger (<45 years old) age groups. In contrast, the distribution of this index was correlated positively with the change in sodium pump inhibition induced by a sodium load (r = 0.415, P> 0.05) and negatively with the fractional excretion of lithium (r = −0.725, P> 0.01). The erythrocyte Na+: K+ ratio tended to be higher in patients with a salt-sensitivity index of 10% than in those with an index of <5%. These results indicate that the salt-sensitivity index is less affected by ageing than by (genetically determined?) sodium reabsorption at proximal tubules; an increase in sodium tubular reabsorption will lead to a rise in blood pressure through stimulation of sodium-pump inhibitor secretion and a consequent increase in intracellular sodium.

A sensitive radioimmunoassay of α human atrial natriuretic polypeptide using monoclonal antibody recognizing human form ring structure

A monoclonal antibody (C351) against alpha human atrial natriuretic polypeptide (alpha hANP) recognizing human form ring structure was established and applied to a radioimmunoassay of plasma alpha hANP. The minimum detectable amount in terms of 10% radioligand displacement relative to zero dose were 0.28 fmol/tube, corresponding to 0.7 fmol/ml in plasma after extraction using Sep-Pak C18 cartridges. When the mean plasma levels at recumbent position in fasted morning were compared in 10 young (less than 30 years) and 10 elderly (greater than or equal to 50 years) healthy subjects taking normal sodium diet, it was slightly higher in the latter (3.2 +/- 0.4 vs 4.7 +/- 0.5 fmol/ml, mean +/- SE, p less than 0.05). After i.v. infusion of hypertonic saline (2.5% NaCl) at a rate of 0.24 ml/kg/min for 20 min in 6 normal subjects (26 to 35 years), it was increased from 4.1 +/- 0.4 to 5.9 +/- 0.7 fmol/ml (p less than 0.01). In 6 patients with essential hypertension (34 to 57 years), it was elevated with high salt intake, i.e. 3.3 +/- 0.3, 3.9 +/- 1.03 and 7.6 +/- 1.5 fmol/ml under 34, 170 and 340 mEq NaCl/day for 7 days, respectively. From these results, the radioimmunoassay of plasma IR-alpha hANP using MAb C351 seems to be quite suitable to detect rather small changes at low plasma concentrations and to investigate a physiological importance of alpha hANP in man.