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

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.

• Clinical pharmacology
• kidney function tests
• kidney function tests
• kidney function tests
• medical biochemistry
• estimation of glomerular filtration rate
• medical biochemistry
• urinanalysis
• medical biochemistry
• renal physiology
• medical physiology

Acknowledgements

Boehringer Mannheim, Germany, kindly supplied the synthetic URO. We thank Lisbeth Mikkelsen for skilful technical assistance. We confirm that there are no professional or financial affiliations that may be perceived to have biased the presentation.