Characterization Of Alpha1-Adrenoceptor Subtypes Mediating Vasoconstriction In Human Umbilical Vein

ANDREA EMILSE ERRASTI, MARÍA PÍA ROGINES VELO, RODRIGO MARTÍN TORRES, SERGIO PABLO SARDI, AND RODOLFO PEDRO ROTHLIN

BRITISH JOURNAL OF PHARMACOLOGY

Nature Publishing Group

Lugar: England; Año: 1999 vol. 126 p. 437 - 442

0007-1188

Characterization of alpha1-adrenoceptor subtypes mediating vasoconstriction in human umbilical vein. Errasti AE, Velo MP, Torres RM, Sardi SP, Rothlin RP. Departamento de Farmacologia, Facultad de Medicina, Universidad de Buenos Aires, Argentina. 1. The present study attempted to characterize pharmacologically the subtypes of alpha-adrenoceptors mediating contractions in human umbilical vein (HUV). 2. HUV rings were mounted in isolated organ baths and cumulative concentration-response curves were constructed for the alpha-adrenoceptor agonists phenylephrine and adrenaline. Adrenaline was more potent than phenylephrine (pD2=7.29 and 6.04 respectively). 3. Isoproterenol exhibited no agonism on KCl pre-contracted HUV rings. Propranolol (1 microM) and rauwolscine (0.1 microM) did not affect the concentration-response curves to adrenaline. These results demonstrate the lack of involvement of functional beta-or alpha2-adrenoceptors in adrenaline-induced vasoconstriction. 4. The non subtype selective alpha1-adrenoceptor antagonist prazosin was evaluated on phenylephrine and adrenaline concentration-response curves. The effects of the competitive alpha1A and alpha1D-adrenoceptor antagonists, 5-methyl urapidil and BMY 7378 and the irreversible alpha1B selective compound chloroethylclonidine (CEC) were also evaluated on adrenaline concentration-response curves. 5. The potencies of prazosin against responses mediated by adrenaline (pA2= 10.87) and phenylephrine (pA2= 10.70) indicate the involvement of prazosin-sensitive functional alpha1-adrenoceptor subtype in vasoconstriction of the HUV. 6. The potencies of 5-methyl urapidil (pA2 = 6.70) and BMY 7378 (pA2= 7.34) were not consistent with the activation of an alpha1A- or alpha1D-adrenoceptor population. 7. Exposure to a relatively low CEC concentration (3 microM) abolished the maximum response to adrenaline suggesting that this response was mediated by an alpha1B-adrenoceptor subtype. 8. We conclude that HUV express a prazosin-sensitive functional alpha1-adrenoceptor resembling the alpha1B-subtype according with the low pA2 values for both 5-methyl urapidil and BMY 7378 and the high sensitivity to CEC. Keywords: Human umbilical vein; a1-adrenoceptors; adrenaline; isoproterenol; rauwolscine; propranolol; prazosin; BMY7378; 5-methyl urapidil; chloroethylclonidine