Renal effects of urodilatin in healthy subjects are independent of blockade of the cyclooxygenase and angiotensin II receptor.

Erling Bjerregaard Pedersen, Jan Carstens

Journal: Scandinavian journal of clinical and laboratory investigation 2008;68(1):2-10

PMID: 17852806

Abstract

OBJECTIVE

Little is known about the role of the renin-angiotensin-aldosterone system and the renal prostaglandins in modulating the renal vasoconstrictive and natriuretic effects of synthetic urodilatin (URO) in healthy humans.

MATERIAL AND METHODS

Twelve volunteers were pretreated in a randomized, single-blind, crossover study with losartan 50 mg a day or placebo for 5 days. Another 12 healthy subjects received indomethacin 25 mg three times a day or placebo for 4 days and a single dose on day 5. All subjects received a URO infusion (15 ng kg(-1) min(-1)) on day 5. Radioactive tracers and the lithium clearance technique were used.

RESULTS

The effective renal plasma flow (ERPF) decreased significantly during URO infusion: losartan pretreatment 573+/-63 to 461+/-76 mL/min versus placebo 540+/-89 to 432+/-90 mL/min. The urinary sodium excretion rate (UNa) increased significantly during URO infusion: losartan 335+/-115 to 502+/-134 umol/min (micromol/min) (UNa) versus placebo 386+/-142 to 476+/-137 umol/min (micromol/min) (UNa). In the indomethacin pretreated subjects, ERPF decreased significantly from 530+/-109 to 446+/-55 mL/min versus 533+/-89 to 449+/-69 mL/min in the placebo group. UNa increased significantly from 395+/-142 to 768+/-254 umol/min (micromol/min) (UNa) in the indomethacin group versus 282+/-117 to 552+/-242 umol/min (micromol/min) (UNa) in placebo.

CONCLUSION

The renal vasoconstrictive and natriuretic effects of synthetic URO are not modified by sustained inhibition of the angiotensin II receptor or the cyclooxygenase in man in a sodium replete state.

Address: Holstebro Hospital, Aarhus University, Department of Medical Research, Holstebro, Denmark. [email protected]

DOI: 10.1080/00365510701504257

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MeSH Terms: Adult, Aldosterone, Angiotensin Receptor Antagonists, Atrial Natriuretic Factor, Blood Pressure, Cross-Over Studies, Cyclic GMP, Diuresis, Diuretics, Glomerular Filtration Rate, Heart Rate, Hematocrit, Humans, Indomethacin, Kidney, Kidney Function Tests, Lithium, Losartan, Male, Natriuresis, Peptide Fragments, Prostaglandin-Endoperoxide Synthases, Prostaglandins, Receptors, Angiotensin, Renal Plasma Flow, Effective, Renin, Single-Blind Method