Dose- and time-dependency of the dilator effects of the endothelin antagonist, BQ-123, in the human forearm.
OBJECTIVE
Endothelin-1 is a potent endogenous vasoconstrictor that acts on the endothelin A (ET[A]) receptor. The dose-response and time-course of the dilator effect of the ET(A) receptor antagonist, BQ-123, was investigated in the forearm of healthy volunteers.


METHODS
Forearm blood flow was measured using mercury-in rubber strain gauge venous occlusion plethysmography.


RESULTS
Following intra-arterial infusion of BQ-123 (50 nmol min-1) for 5 min, forearm blood flow increased by approximately 60% over the next 60 minutes; lower doses were without significant effect. The degree of dilatation was similar to that observed in previous studies using 20-fold larger doses.


CONCLUSIONS
This study confirms that basal endothelin-1 has a role in the physiological regulation of vascular tone. It is possible that at low doses, BQ-123 might be a more sensitive pharmacological tool for the detection of abnormal endothelin-1 mediated constriction.
Berrazueta
J R
JR
Department of Medicine, Cantabria University of Spain, Santander.
Bhagat
K
K
Vallance
P
P
MacAllister
R J
RJ
D000328:Adult; D004305:Dose-Response Relationship, Drug; D065128:Endothelin Receptor Antagonists; D005260:Female; D005542:Forearm / Q000098:blood supply*; D006801:Humans; D008297:Male; D010456:Peptides, Cyclic / Q000494:pharmacology*; D010991:Plethysmography; D012039:Regional Blood Flow / Q000187:drug effects; D013997:Time Factors; D014665:Vasodilator Agents / Q000494:pharmacology*
D065128:Endothelin Receptor Antagonists; D010456:Peptides, Cyclic; D014665:Vasodilator Agents; C072247:cyclo(Trp-Asp-Pro-Val-Leu)