| Abstract
| - Background. To analyse whether congenital furosemide- or thiazide-like renal salt loss protects against the potential prohypertensive effects of two cyclooxygenase (COX) inhibitors: rofecoxib, a COX-2 selective inhibitor, and indomethacin, an unselective COX-inhibitor. Methods. In a retrospective analysis, the effects of rofecoxib and indomethacin on blood pressure (bp: transformed into age-independent standard deviation scores (SDS) values), creatinine clearance (CRC), fractional excretion of sodium (FeNa), and renal excretion of systemic prostaglandins were studied in 28 patients with a genetically proven congenital hypokalaemic salt-losing tubulopathy (SLT) (11 female and 17 male, age: 2-25 years), 19 with a furosemide-like SLT, and nine with a thiazide-like SLT. Results. In furosemide-like SLT patients, systolic SDS bp values were significantly higher with rofecoxib (1.03±0.16 SDS, n = 107) compared with indomethacin (0.56±0.09 SDS, n = 282; P = 0.007, 95% CI: 0.12-0.8). Without the drugs, systolic SDS bp values were elevated by 0.63±0.11 SDS, n = 164. Both drugs reduced renin and aldosterone-plasma levels to a similar extent. SDS values were significantly correlated with the excretion of the vasoconstrictor thromboxane (T × B2) (R2: 0.038, P = 0.021, n: 159), but not with CRC or FeNa. Blood pressure was not increased in thiazide-like SLT patients treated with rofecoxib. Conclusion. Congenital furosemide-like renal salt loss does not protect against the prohypertensive effects of rofecoxib. The positive correlation between bp SDS values with T × B2 but not with FeNa or CRC point towards an altered vascular homeostasis as one mechanism increasing blood pressure.
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