Urocortin 2 infusion in healthy humans: hemodynamic, neurohormonal, and renal responses.
OBJECTIVE
We sought to examine the effects of urocortin (UCN) 2 infusion on hemodynamic status, cardiovascular hormones, and renal function in healthy humans.


BACKGROUND
Urocortin 2 is a vasoactive and cardioprotective peptide belonging to the corticotrophin-releasing factor peptide family. Recent reports indicate the urocortins exert important effects beyond the hypothalamo-pituitary-adrenal axis upon cardiovascular and vasohumoral function in health and cardiac disease.


METHODS
We studied 8 healthy unmedicated men on 3 separate occasions 2 to 5 weeks apart. Subjects received placebo, 25-microg low-dose (LD), and 100-microg high-dose (HD) of UCN 2 intravenously over the course of 1 h in a single-blind, placebo-controlled, dose-escalation design. Noninvasive hemodynamic indexes, neurohormones, and renal function were measured.


RESULTS
The administration of UCN 2 dose-dependently increased cardiac output (mean peak increments +/- SEM) (placebo 0.5 +/- 0.2 l/min; LD 2.1 +/- 0.6 l/min; HD 5.0 +/- 0.8 l/min; p < 0.001), heart rate (placebo 3.3 +/- 1.0 beats/min; LD 8.8 +/- 1.8 beats/min; HD 17.8 +/- 2.1 beats/min; p < 0.001), and left ventricular ejection fraction (placebo 0.6 +/- 1.4%; LD 6.6 +/- 1.5%; HD 14.1 +/- 0.8%; p < 0.001) while decreasing systemic vascular resistance (placebo -128 +/- 50 dynes x s/cm(5); LD -407 +/- 49 dynes x s/cm(5); HD -774 +/- 133 dynes.s/cm(5); p < 0.001). Activation of plasma renin activity (p = 0.002), angiotensin II (p = 0.001), and norepinephrine (p < 0.001) occurred only with the higher 100-mug dose. Subtle decreases in urine volume (p = 0.012) and natriuresis (p = 0.001) were observed.


CONCLUSIONS
Brief intravenous infusions of UCN 2 in healthy humans induced pronounced dose-related increases in cardiac output, heart rate, and left ventricular ejection fraction while decreasing systemic vascular resistance. Subtle renal effects and activation of plasma renin, angiotensin II, and norepinephrine (at high-dose only) were observed. These findings warrant further investigation of the role of UCN 2 in circulatory regulation and its potential therapeutic application in heart disease.
Davis
Mark E
ME
Christchurch Cardioendocrine Research Group, Christchurch School of Medicine and Health Sciences, Christchurch, New Zealand. mark.davis@chmeds.ac.nz
Pemberton
Christopher J
CJ
Yandle
Timothy G
TG
Fisher
Steve F
SF
Lainchbury
John G
JG
Frampton
Christopher M
CM
Rademaker
Miriam T
MT
Richards
A Mark
AM
D000328:Adult; D000804:Angiotensin II / Q000097:blood* / Q000187:drug effects; D003346:Corticotropin-Releasing Hormone / Q000008:administration & dosage / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D007262:Infusions, Intravenous; D007668:Kidney / Q000187:drug effects* / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D009318:Natriuresis / Q000187:drug effects*; D009638:Norepinephrine / Q000097:blood*; D012083:Renin / Q000097:blood* / Q000187:drug effects; D016037:Single-Blind Method; D013318:Stroke Volume / Q000187:drug effects*; D014556:Urine; D054832:Urocortins; D014655:Vascular Resistance / Q000187:drug effects*
C426705:UCN2 protein, human; D054832:Urocortins; D000804:Angiotensin II; D003346:Corticotropin-Releasing Hormone; D012083:Renin; D009638:Norepinephrine