Increased systolic blood pressure with rofecoxib in congenital furosemide-like salt loss.
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 x 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.


CONCLUSIONS
Congenital furosemide-like renal salt loss does not protect against the prohypertensive effects of rofecoxib. The positive correlation between bp SDS values with T x B2 but not with FeNa or CRC point towards an altered vascular homeostasis as one mechanism increasing blood pressure.
Department of Pediatrics, Philipps University Marburg, D-35033 Marburg, Germany. koemhoff@med.uni-marburg.de
Martin
M
Kömhoff
Günter
G
Klaus
Sofia
S
Nazarowa
Stephan C
SC
Reinalter
Hannsjörg W
HW
Seyberth
D000293:Adolescent; D000328:Adult; D001794:Blood Pressure; D002648:Child; D002675:Child, Preschool; D051546:Cyclooxygenase 2 / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D005260:Female; D005665:Furosemide / Q000494:pharmacology*; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D007783:Lactones / Q000494:pharmacology*; D008297:Male; D012189:Retrospective Studies; D012737:Sex Factors; D013450:Sulfones / Q000494:pharmacology*; D013599:Systole; D013997:Time Factors
D052246:Cyclooxygenase 2 Inhibitors; D007783:Lactones; D013450:Sulfones; C116926:rofecoxib; D005665:Furosemide; D051546:Cyclooxygenase 2; D007213:Indomethacin