Effects of prostacyclin on renal haemodynamics, renal tubular function and vasoactive hormones in healthy humans. A placebo-controlled dose-response study.
OBJECTIVE
To investigate the acute effects of prostacyclin (Flolan) on renal haemodynamics, renal tubular function, plasma concentration of angiotensin II (Ang II), aldosterone (Aldo), atrial natriuretic peptide (ANP), arginine vasopressin (AVP), mean arterial blood pressure (MBP), and heart rate (HR).


METHODS
Thirteen healthy control subjects were investigated on two separate occasions in a placebo controlled, randomized, dose-response study of the effect of intravenous infusion of prostacyclin (PGI2, Flolan, 2, 4 and 8 ng kg(-1) min(-1)). Glomerular filtration rate (GFR) and renal plasma flow (RPF) were measured by the use of constant infusion of [51Cr]-EDTA and [125I]-hippurane. Urinary output, urinary sodium excretion, fractional sodium excretion, fractional lithium excretion were measured and hormones were measured using radioimmunoassay.


RESULTS
During prostacyclin (PGI2) infusion we observed a significant increase in RPF (PGI2: 4.8%; 6.1% and 5.2% vs Plac: -1.5%; -1.9% and -5.8% for 2, 4 and 8 ng kg(-1) min(-1) respectively; P < or = 0.05 for 4 and 8 ng kg(-1) min(-1)) in Ang II (PGI2: 20.0%; 42.9% and 88.9% vs Plac: 0.1%; 8.0% and 0.0%, P < or = 0.01 for 4 and 8 ng kg(-1) min(-1)) in ANP (PGI2: 13.6%; 12.7% and 37.5% vs Plac: -10.2%; -6.6% and -2.4%, P < or = 0.05 for 2 ng kg(-1) min(-1) and P < or = 0.01 for 4 and 8 ng kg(-1) min(-1)), and in HR (PGI2: 8.8%; 17.6% and 32.7% vs Plac: 0.8%; 4.1% and 3.5%, P < or = 0.05 for 2 and P < or = 0.01 for 4 and 8 ng kg(-1) min(-1)). A significant decrease was observed in MBP (MBP:PGI2: -1.7%; -1.9% and -5.6% vs Plac: -0.4%; -1.6% and +2.1%, P < or = 0.01 for 8 ng kg(-1) min(-1)). No significant changes were seen in the other effect variables.


CONCLUSIONS
Infusion of prostacyclin in healthy control subjects increases renal plasma flow, angiotensin II, atrial natriuretic peptide, and heart rate and decreases mean blood pressure. Furthermore prostacyclin infusion does not change net sodium excretion in healthy controls.
Nielsen
C B
CB
Research Laboratory of Nephrology and Hypertension Aarhus University Hospital, Aarhus C, Denmark.
Bech
J N
JN
Pedersen
E B
EB
D000328:Adult; D000450:Aldosterone / Q000097:blood*; D000804:Angiotensin II / Q000097:blood*; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001127:Arginine Vasopressin / Q000097:blood*; D009320:Atrial Natriuretic Factor / Q000097:blood*; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D011464:Epoprostenol / Q000494:pharmacology*; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007684:Kidney Tubules / Q000187:drug effects* / Q000502:physiology; D008094:Lithium / Q000493:pharmacokinetics / Q000652:urine; D008297:Male; D010919:Placebos; D012079:Renal Circulation / Q000187:drug effects*; D012964:Sodium / Q000652:urine
D000959:Antihypertensive Agents; D010919:Placebos; D000804:Angiotensin II; D001127:Arginine Vasopressin; D000450:Aldosterone; D009320:Atrial Natriuretic Factor; D008094:Lithium; D012964:Sodium; D011464:Epoprostenol