Venous response to nitroglycerin is enhanced in young, healthy carriers of the 825T allele of the G protein beta3 subunit gene (GNB3).
OBJECTIVE
The ultimate mode of action by which nitroglycerin elicits vasodilation remains elusive. Animal studies point to an involvement of pertussis toxin-sensitive G proteins. The 825T allele of the GNB3 C825T polymorphism in the gene encoding the G protein beta3 subunit is associated with enhanced signal transduction via pertussis toxin-sensitive pathways in vitro. We hypothesized that G proteins have a role in nitroglycerin-mediated vasodilation and that carriers of the 825T allele would exhibit a stronger response to nitroglycerin.


METHODS
We used the linear variable transducer technique to compare dorsal hand vein compliance in 28 young, healthy men with and without the T allele (n = 15 CC, n = 8 CT, and n = 5 TT). After individual dose-response curves to phenylephrine had been established, veins were preconstricted to 70% of the maximal phenylephrine-induced constriction. Nitroglycerin was then infused in ascending doses (0.02-2000 ng/min), and the vasodilatory response was measured.


RESULTS
The vasodilatory response to nitroglycerin was significantly greater in carriers of the 825T allele. The maximal response to nitroglycerin was 102% +/- 6% venodilation in the CT/TT group and 78% +/- 5% in the CC control group (P =.0045) (mean difference, -24% +/- 8%; 95% confidence interval, 8%-40%). Comparison of the nitroglycerin dose-response curves by ANOVA confirmed an enhanced nitroglycerin-induced venodilation in 825T-allele carriers (P <.0001).


CONCLUSIONS
Our results suggest that the GNB3 C825T polymorphism determines venous response to nitroglycerin and that G proteins may be involved in the signal transduction pathway.
Departments of Nephrology & Hypertension and Pharmacology, Essen University, Essen, Germany. anna.mitchell@uni-esen.de
Anna
A
Mitchell
Sandra
S
Bührmann
Anne
A
Seifert
Jens
J
Nürnberger
René R
RR
Wenzel
Winfried
W
Siffert
Thomas
T
Philipp
Rafael F
RF
Schäfers
D000328:Adult; D000483:Alleles; D015992:Body Mass Index; D004305:Dose-Response Relationship, Drug; D006225:Hand / Q000098:blood supply; D020962:Heterotrimeric GTP-Binding Proteins / Q000235:genetics*; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D005996:Nitroglycerin / Q000494:pharmacology*; D011110:Polymorphism, Genetic / Q000235:genetics; D012039:Regional Blood Flow / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*
C454420:G-protein beta3 subunit; D014665:Vasodilator Agents; D020962:Heterotrimeric GTP-Binding Proteins; D005996:Nitroglycerin