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


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.


CONCLUSIONS
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.
Carstens
Jan
J
Holstebro Hospital, Aarhus University, Department of Medical Research, Holstebro, Denmark. drjc@dadlnet.dk
Pedersen
Erling Bjerregaard
EB
D000328:Adult; D000450:Aldosterone / Q000097:blood; D057911:Angiotensin Receptor Antagonists; D009320:Atrial Natriuretic Factor / Q000008:administration & dosage / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D018592:Cross-Over Studies; D006152:Cyclic GMP / Q000097:blood; D004231:Diuresis / Q000187:drug effects; D004232:Diuretics / Q000008:administration & dosage / Q000494:pharmacology; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006400:Hematocrit; D006801:Humans; D007213:Indomethacin / Q000008:administration & dosage / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D007677:Kidney Function Tests; D008094:Lithium / Q000652:urine; D019808:Losartan / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D009318:Natriuresis / Q000187:drug effects; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D011453:Prostaglandins / Q000378:metabolism; D011945:Receptors, Angiotensin / Q000378:metabolism*; D017596:Renal Plasma Flow, Effective / Q000187:drug effects; D012083:Renin / Q000097:blood; D016037:Single-Blind Method
D057911:Angiotensin Receptor Antagonists; D004232:Diuretics; D010446:Peptide Fragments; D011453:Prostaglandins; D011945:Receptors, Angiotensin; D000450:Aldosterone; C056452:Ularitide; D009320:Atrial Natriuretic Factor; D008094:Lithium; D011451:Prostaglandin-Endoperoxide Synthases; D012083:Renin; D006152:Cyclic GMP; D019808:Losartan; D007213:Indomethacin