Characterization of alpha(1)-adrenoceptor subtypes mediating vasoconstriction in human umbilical vein

1 The present study attempted to characterize pharmacologically the subtype s of alpha-adrenoceptors mediating contractions in human umbilical vein (HU V). 2 HUV rings were mounted in isolated organ baths and cumulative concentrati on-response curves were constructed for the alpha-adrenoceptor agonists phe nylephrine and adrenaline. Adrenaline was more potent than phenylephrine (p D(2) = 7.29 and 6.04 respectively). 3 Isoproterenol exhibited no agonism on KCl pre-contracted HUV rings. Propr anolol (1 mu M) and rauwolscine (0.1 mu M) did not affect the concentration -response curves to adrenaline. These results demonstrate the lack of invol vement of functional beta- or alpha(2)-adrenoceptors in adrenaline-induced vasoconstriction. 4 The non subtype selective alpha(1)-adrenoceptor antagonist prazosin was e valuated on phenylephrine and adrenaline concentration-response curves. The effects of the competitive alpha(1A) and alpha(1D)-adrenoceptor antagonist s, 5-methyl urapidil and BMY 7378 and the irreversible alpha(1B) selective compound chloroethylclonidine (CEC) were also evaluated on adrenaline conce ntration-response curves. 5 The potencies of prazosin against responses mediated by adrenaline (pA(2) = 10.87) and phenylephrine (pA(2) = 10.70) indicate the involvement of pra zosin-sensitive functional alpha(1)-adrenoceptor subtype in vasoconstrictio n of the HUV. 6 The potencies of 5-methyl urapidil (pA(2) = 6.70) and BMY 7378 (pA(2) = 7 .34) were not consistent with the activation of an alpha(1A)- or alpha(1D)- adrenoceptor population. 7 Exposure to a relatively low CEC concentration (3 mu M) abolished the max imum response to adrenaline suggesting that this response was mediated by a n alpha(1B)-adrenoceptor subtype. 8 We conclude that HUV express a prazosin-sensitive functional alpha(1)-adr enoceptor resembling the alpha(1B)-subtype according with the low pA(2) val ues for both 5-methyl urapidil and BMY 7378 and the high sensitivity to CEC .