In this study we analyzed the different α1-adrenoceptor (AR) subtypes present in human saphenous vein (HSV) using reverse transcription polymerase chain reaction (RT-PCR), DNA-DNA hybridization analysis and functional affinities for α-AR antagonists. DNA-DNA hybridization analysis of RT-PCR amplification products confirmed the presence of α1A- and α1B-ARs, and low levels of α1D-AR in HSV. The functional results showed: (1) prazosin, the selective α1-AR antagonist, phentolamine, the α1- and α2-ARs antagonist, WB 4101 and 5-MU, the selective α1A-AR subtype antagonists were potent, competitive antagonists of noradrenaline (NA)-induced contraction (pA2 values of 11.03, 8.06, 9.02 and 8.34, respectively). (2) α1-AR-induced contraction was sensitive to the alkylating effects of CEC (the α1B and α1D-AR subtypes antagonist) and (3) The selective α1D-AR subtype antagonist BMY displayed low affinity (pA2 values of 6.44). This indicates that the contractile response of the HSV to α1-AR-induced is predominantly mediated by both α1A and α1B-AR subtypes. This was also supported by the good relationship between pA2 values from the present study and reported binding affinities (pKi) values of various α1-AR subtype antagonists with cloned human α1A- and α1B-AR subtypes (r=0.89 and r=0.98, respectively), but not the α1D-AR subtype (r=0.67). Our results indicate that α1A- and α1B-ARs are the main functional and expressed receptor subtypes in HSV.
- α-adrenoceptor subtypes
- Human saphenous vein
- Vascular smooth muscle contraction