Marked synergism between vasopressin and angiotensin II in a human isolated artery.
OBJECTIVE
To determine the direct contractile effects of angiotensin II (AII) and vasopressin (VP), and the effects of combinations of these agonists, in human isolated gastroepiploic arteries in vitro.


METHODS
Laboratory and clinical investigation.


METHODS
University laboratory and hospital.


METHODS
Ring segments were prepared from gastroepiploic arteries obtained from 57 patients undergoing gastrectomy. Blood samples were obtained from ten patients after severe hemorrhage and from five healthy volunteers.


METHODS
Mechanical activity in the rings was assessed using a strain gauge. Plasma concentrations of AII and VP in the blood samples were measured using radioimmunoassay kits.


RESULTS
Both AII (1 or 10 ng/mL) and VP (100 or 500 pg/mL) produced concentration-dependent contractions in the rings. However, whereas VP produced reproducible sustained contractions, the contractile responses induced by multiple applications of AII showed marked desensitization (i.e., tachyphylaxis). Indeed, by the sixth application of either 1 ng/mL AII or 10 ng/mL AII, the contractile responses were <20% of the initial (control) response. During applications of AII after the sixth, the co-application of a low concentration of VP (100 pg/mL) fully restored the contractile response to AII in a clearly more-than-additive fashion. Similarly, the tachyphylaxis seen on AII application alone did not occur with repeated applications of an AII + norepinephrine mixture. In patients who had experienced hemorrhage, there were marked elevations of both AII and VP plasma concentrations, with values as high as 2.2 ng/mL and 550 pg/mL, respectively.


CONCLUSIONS
These results indicate that there is a powerful synergism between the contractile effects of low-dose VP and AII in this human isolated artery. Moreover, the elevations of plasma AII and VP levels during hemorrhage suggest that this synergism may be both physiologically and clinically important in optimizing vasoconstriction and maintaining blood pressure in such critical states.
Hidaka
Tatewaki
T
Department of Anesthesiology and Critical Care Medicine, Kagoshima University School of Medicine, Kagoshima, Japan.
Tsuneyoshi
Isao
I
Boyle
Walter A
WA
Onomoto
Masanori
M
Yonetani
Shin
S
Hamasaki
Junichirou
J
Katai
Rumi
R
Kanmura
Yuichi
Y
D000328:Adult; D000368:Aged; D000804:Angiotensin II / Q000097:blood / Q000494:pharmacology*; D001158:Arteries / Q000187:drug effects; D004730:Endothelium, Vascular / Q000187:drug effects; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000097:blood / Q000494:pharmacology*; D014667:Vasopressins / Q000097:blood / Q000494:pharmacology*
D014662:Vasoconstrictor Agents; D014667:Vasopressins; D000804:Angiotensin II