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CARDIOVASCULAR

Differential Distribution of Functional ₁-Adrenergic Receptor Subtypes along the Rat Tail Artery

Departments of Pharmacology (S.Y.K., A.M., V.L., A.R.T.S., A.S.P.) and Physiology (I.B.d.C., J.B.), Instituto de Biociências, Universidade Estadual Paulista, Botucatu, São Paulo, Brazil

The rat tail artery has been used for the study of vasoconstriction mediated by _1A-adrenoceptors (ARs). However, rings from proximal segments of the tail artery (within the initial 4 cm, PRTA) were at least 3-fold more sensitive to methoxamine and phenylephrine (n = 6–12; p < 0.05) than rings from distal parts (between the sixth and 10th cm, DRTA). Interestingly, the imidazolines N-[5-(4,5-dihydro-1H-imidazol-2-yl)-2-hydroxy-5,6,7,8-tetrahydronaphthalen-1-yl]methanesulfonamide hydrobromide (A-61603) and oxymetazoline, which activate selectively _1A-ARs, were equipotent in PRTA and DRTA (n = 4–12), whereas buspirone, which activates selectively _1D-AR, was 70-fold more potent in PRTA than in DRTA (n = 8; p < 0.05). The selective _1D-AR antagonist 8-[2-[4-(methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspiro[4.5]decane-7,9-dione dihydrochloride (BMY-7378) was 70-fold more potent against the contractions induced by phenylephrine in PRTA (pK_B of 8.45; n = 6) than in DRTA (pK_B of 6.58; n = 6), although the antagonism was complex in PRTA. 5-Methylurapidil, a selective _1A-antagonist, was equipotent in PRTA and DRTA (pK_B of 8.4), but the Schild slope in DRTA was 0.73 ± 0.05 (n = 5). The noncompetitive _1B-antagonist conotoxin -TIA reduced the maximal contraction induced by phenylephrine in DRTA, but not in PRTA. These results indicate a predominant role for _1A-ARs in the contractions of both PRTA and DRTA but with significant coparticipations of _1D-ARs in PRTA and _1B-ARs in DRTA. Semiquantitative reverse transcription-polymerase chain reaction revealed that mRNA encoding _1A- and _1B-ARs are similarly distributed in PRTA and DRTA, whereas mRNA for _1D-ARs is twice more abundant in PRTA. Therefore, ₁-ARs subtypes are differentially distributed along the tail artery. It is important to consider the segment from which the tissue preparation is taken to avoid misinterpretations on receptor mechanisms and drug selectivities.

Address correspondence to: Dr. André Sampaio Pupo, Department of Pharmacology, Instituto de Biociências, UNESP, Botucatu, São Paulo, Brazil, 18618-000. E-mail: aspupo{at}ibb.unesp.br

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