Enhanced blood pressure response to cyclooxygenase inhibition in salt-sensitive human essential hypertension.

Abstract

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.

Age‐Dependent Influence on Heart Rate Variability in Salt‐sensitive Hypertensive Subjects

“…Immediately afterward, they began a 7‐day placebo‐supplemented diet, supplying a daily sodium intake of 20 mEq of Na + (low‐salt diet). Hypertensive patients were denned as salt sensitive if their DBP decreased by 10 mm Hg or more between the high and low sodium intakes 15,42–44 . The two diets had an equal number of calories and an equal Na + content.…”

Renal Changes Induced by Nitric Oxide and Prostaglandin Synthesis Reduction

“…In support of this hypothesis, it has been reported that NO synthesis seems to be reduced in salt-sensitive hypertension 6 and that the administration of a cyclooxygenase inhibitor induces an increase of arterial pressure in salt-sensitive hypertensive patients. 7 Recent studies of our group have demonstrated that captopril (0.8 g ⅐ kg Ϫ1 ⅐ min Ϫ1 ) is only effective in treating the renal vasoconstriction, 3 and verapamil (2 g ⅐ kg Ϫ1 ⅐ min Ϫ1 ) is effective in treating the antinatriuretic effects 8 induced by acute meclofenamate administration, when NO is reduced. Based on these findings and on the well-known pharmacological actions of calcium antagonists and CEIs, 9 -11 it could be expected that the combination of the two drugs would be effective in treating both renal effects produced by the acute inhibition of PG synthesis when NO production is reduced.…”

Celecoxib does not alter cardiovascular and renal function during dietary salt loading

“…Statistical significance was set at P < 0.05. Based on data from Ferri et al 27 12 subjects would allow us > 80% power to detect a 5 mmHg increase in systolic BP, a 3 mmHg increase in diastolic BP and a 15% reduction in sodium excretion from COX inhibition.…”

“…For example, Ferri et al 27 demonstrated that indomethacin resulted in impaired renal sodium excretion and increased BP in hypertensive subjects who were determined to have 'salt-sensitive' BP, but not in those determined to be 'salt resistant'. In the present study, our focus was to examine the effect of a clinical dose of a selective COX-2 inhibitor on urinary parameters and BP in a group of middle-aged adults without regard Data are the mean ± SEM *P < 0.05 compared with the low-salt (LS) diet; † P < 0.05 compared with placebo.…”