The effects of urotensin II and urantide on forearm blood flow and systemic haemodynamics in humans.
OBJECTIVE
(i) To compare the effects of intra-arterial administration of urotensin II in patients with CVD with healthy volunteers, and (ii) to study the haemodynamic effects of intra-arterial infusion of the urotensin II receptor antagonist, urantide.


METHODS
Ten healthy volunteers and 10 patients with CVD received a dose-ramped brachial artery infusion of urotensin II. A further six healthy male volunteers received a prolonged urotensin II infusion and 11 healthy male volunteers received a dose-ramped infusion of urantide. Forearm blood flow (FBF) was measured every 20 min and blood pressure and heart rate were assessed every 20 min.


RESULTS
In healthy volunteers and patients with CVD, intra-arterial infusion of urotensin II had no effect on FBF ratio. A dose-ramped infusion of urantide similarly had no effect on FBF ratio. During dose-ramped infusions of urotensin II and urantide, systolic and mean arterial blood pressure increased significantly. In healthy volunteers, urotensin II and urantide, respectively, increased systolic blood pressure from 133 +/- 6 to 137 +/- 5 mmHg (P < 0.01) and from 113 +/- 4 to 120 +/- 4 mmHg (P < 0.01). In patients with CVD, heart rate also significantly increased during dose-ramped infusion of urotensin II from 59 +/- 3 to 62 +/- 4 bpm (P < 0.05).


CONCLUSIONS
We have shown no in vivo effect of urotensin II or urantide on human forearm resistance vessels. Previous discrepancies do not seem to relate to either the age or CVD status of subjects. Changes in systemic cardiovascular haemodynamics during the dose-ramped infusion studies are unlikely to be caused by urotensin II receptor modulation.
Cheriyan
Joseph
J
Clinical Pharmacology Unit, Addenbrooke's Hospital, University of Cambridge, Cambridge CB2 2QQ, UK.
Burton
Timothy J
TJ
Bradley
Timothy J
TJ
Wallace
Sharon M L
SM
Mäki-Petäjä
Kaisa M
KM
Mackenzie
Isla S
IS
McEniery
Carmel M
CM
Brown
John
J
Wilkinson
Ian B
IB
D000328:Adult; D001794:Blood Pressure / Q000187:drug effects*; D002318:Cardiovascular Diseases / Q000188:drug therapy; D016022:Case-Control Studies; D005542:Forearm / Q000098:blood supply*; D006339:Heart Rate / Q000187:drug effects*; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D007261:Infusions, Intra-Arterial; D008297:Male; D010446:Peptide Fragments / Q000008:administration & dosage / Q000187:drug effects*; D012039:Regional Blood Flow / Q000187:drug effects; D016896:Treatment Outcome; D014579:Urotensins / Q000008:administration & dosage / Q000187:drug effects*; D055815:Young Adult
D010446:Peptide Fragments; D014579:Urotensins; C492079:urotensin II (4-11), Pen(5)-Trp(7)-Orn(8)-