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Characterization of subtype of alpha 1-adrenoceptor mediating vasoconstriction in perfused rat mesenteric vascular

W Z Zhu¹, Y Y Zhang, Q D Han

¹Institute of Vascular Medicine, Third Hospital, Beijing Medical University, China.

Zhongguo Yao Li Xue Bao = Acta Pharmacologica Sinica

|August 7, 1999

Abstract

Aim:

To characterize the subtype of alpha 1-adrenoceptor mediating vasoconstriction in perfused rat mesenteric vascular bed.

Methods:

The potencies (pA2 values determined by Schild plot) of alpha 1-adrenoceptor-selective antagonists were determined by isolated vasoconstrictive experiment. The pKi values were determined by 125I-BE 2254 binding from the cloned alpha 1A-, alpha 1B-, and alpha 1D-adrenoceptor, stably expressed in human embryonic kidney (HEK) 293 cells.

Results:

The pA2 values for alpha 1A-adrenoceptor-selective antagonists, RS-17053, WB 4101, 5-methyl-urapidil, and the alpha 1D-adrenoceptor-selective antagonist, BMY 7378, were 8.98 +/- 0.28, 9.16 +/- 0.20, 8.69 +/- 0.02, and 6.03 +/- 0.26, respectively, with the slope not different from unity. The pA2 values of the above antagonists correlated well with the binding pKi values only for alpha 1A-adrenoceptors (r = 0.97), but not for alpha 1B-adrenoceptors (r = 0.52) and alpha 1D-adrenoceptors (r = 0.04). The concentration-vasopressor response curve for norepinephrine was not affected by pretreatment with chloroethylclonidine (Chl) 50 mumol.L-1 for 30 min.

Conclusion:

Only alpha 1A-adrenoceptors mediate the norepinephrine-induced vasopressor response in perfused rat mesenteric vascular bed.

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