Our findings indicate that circulating ET-1 levels significantly increase during euglycemic hyperinsulinemic clamp in men with NIDDM. The negative correlation between total glucose uptake and circulating ET-1 levels suggests that the peptide might exert negative effects on the insulin sensitivity of target tissues. The consequent increase in insulin secretion as well as the insulin-related ET-1 release from endothelial cells could favor the development of diabetes-related vascular lesions.

A strong influence of urinary kallikrein excretion on the salt sensitivity of blood pressure has been recently suggested in normotensive patients. To evaluate the relationship between kallikrein and salt sensitivity in essential hypertension, active kallikrein excretion, plasma renin activity, atrial natriuretic peptide and aldosterone levels were evaluated in 37 male hypertensives (mean age 43.3 +/- 4.7 years) after two weeks on a normal NaCl diet (120 mmol NaCl per day). After kallikrein determination, salt sensitivity was assessed in a randomized cross-over double-blind fashion by evaluating the blood pressure response to a high (240 mmol NaCl per day for two weeks) and a low (40 mmol NaCl per day for 2 weeks) NaCl intake. Blood pressure changes were evaluated considering as baseline blood pressure the measurement taken at the end of the 2 weeks under normal NaCl intake. Patients were classified as salt sensitive when a diastolic blood pressure change of 10 mm Hg or more occurred after both periods of low and high NaCl intake. At the end of the assessment of salt sensitivity, 19 hypertensive patients (mean age 43.0 +/- 4.6 years) were resistant. The urinary excretion of active kallikrein was significantly lower (P < 0.0001) in salt sensitive (0.51 +/- 0.36 U/24 hr) than in salt resistant patients (1.28 +/- 0.48 U/24 hr). Also, plasma atrial natriuretic peptide levels were higher in salt sensitive than in salt resistant hypertensives (P < 0.02), and a significant correlation between urinary kallikrein and plasma atrial natriuretic peptide was demonstrated in salt sensitive hypertensives (r = -0.691, P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

To evaluate the influence of salt sensitivity on the blood pressure response to oral indomethacin treatment, we studied 35 hospitalized essential hypertensive patients (24 men and 11 women, aged from 40 to 55 years). During a normal NaCl intake (120 mmol Na + per day), patients were assigned to receive in a randomized double-blind fashion either 200 rag indomethacin (25 patients) or placebo (10 patients) for 5 days. Two weeks after the interruption of indomethacin treatment, during which the normal NaCl intake was continued, salt sensitivity was assessed by giving each patient a high (220 mmol Na + per day for 10 days) and then a low (20 mmol Na + per day for 10 days) NaCl diet Blood pressure changes were evaluated, and the measurement taken at the end of the 2 weeks under normal sodium intake was considered baseline blood pressure. Patients were classified as salt sensitive when a diastolic blood pressure change of 10 mm Hg or more occurred after both low and high periods of sodium intake. In salt-resistant patients treated with indomethacin (n = 12, nine men and three women, mean age 50.5±3.7 years), neither blood pressure (systolic blood pressure from 150.8±11.2 to 154.6±9J mm Hg, NS; diastolic blood pressure from 99.3 ±2.1 to 101.1 ±4.4 mm Hg, NS) nor the urinary Na + excretion (from 108.1±20.9 to 97.9±9.1 mmol/24 hr, NS) was significantly affected by the drug. On the contrary, when compared with patients receiving placebo (five men and five women, mean age 44.4±4.1 years), salt-sensitive hypertensive patients (n=13, 10 men and three women, mean age 47.9 ±6.5 years) showed significantly higher levels (p< 0.004) of diastolic blood pressure after indomethacin therapy. According to these data, compared with pretreatment values blood pressure significantly increased in salt-sensitive patients after indomethacin treatment (systolic blood pressure from 156.9±9.7 to 163.5±10.8 mm Hg, p<0.001; diastolic blood pressure from 98.5±2.1 to 105.7±5.7 mm Hg,p<0.006) despite a marked plasma renin activity (from 0.18±0.14 to 0.10±0.09 ng/L per second,p<0.02) and aldosterone (from 390.5±154.9 to 299.3±169.5 pmol/L,p<0.002) decrease. Salt-sensitive patients also showed a significant indomethacin-related decrease of urinary Na + excretion (from 108.1±11.6 to 90.9±10.1 mmol/24 hr,p<0.04). Our results indicate that the blood pressure response to indomethacin depends on salt sensitivity in human essential hypertensive patients. The increase of blood pressure, observed in salt-sensitive hypertensive patients, is followed by a significant reduction in urinary Na + excretion. This finding suggests that the indomethacin-induced decrease in Na + excretion is responsible for the blood pressure increase showed by salt-sensitive patients after oral indomethacin treatment.

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