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An alpha(1A)/alpha(1L)-adrenoceptor mediates contraction of canine subcutaneous resistance arteries



An alpha(1A)/alpha(1L)-adrenoceptor mediates contraction of canine subcutaneous resistance arteries



Journal of Pharmacology and Experimental Therapeutics 295(2): 627-633



To determine the characteristics of the alpha(1)-adrenoceptor subtypes involved in adrenergic regulation of peripheral vascular resistance, contraction of canine subcutaneous resistance arteries was studied using wire myographs. The potencies of agonists and antagonists, chosen for their ability to discriminate between alpha(1)-adrenoceptor subtypes, were assessed in the presence of cocaine (3 microM), corticosterone (30 microM), and propranolol (1 microM). The rank order of agonist potency (pEC(50) +/- S.E.) was (R)-A-61603 (7.88 +/- 0.1) > norepinephrine (6.41 +/- 0.1) > phenylephrine (5.83 +/- 0.1). The high sensitivity to (R)-A-61603 relative to phenylephrine is inconsistent with the presence of the alpha(1D)-adrenoceptor and most consistent with an alpha(1A)-adrenoceptor response. This is supported by the low affinity for the alpha(1D)-selective antagonist BMY 7378 (pK(B) 6.51 +/- 0.47). The low pA(2) values for prazosin (8.36) and HV723 (8.81), by definition, indicate the involvement of the putative alpha(1L)-adrenoceptor, a hypothesis supported by the pA(2) values for WB4101 (8.42) and 5-methyl-urapidil (8.08). Pre-exposure to 1 microM CEC had little effect, whereas 100 microM CEC reduced the maximum contraction but not the sensitivity to norepinephrine. This low sensitivity to CEC argues against the presence of the alpha(1B)-adrenoceptor. We conclude that, by current definitions, an alpha(1A)-/alpha(1L)-adrenoceptor causes contraction of these vessels. This does not support the concept that selectivity for the alpha(1A)-adrenoceptor is the basis for the effectiveness of some alpha-blockers in some tissues, such as prostate, but not in other tissues such as blood vessels. Rather, the generally low potency of alpha-blockers in some tissues may be due to a tissue-specific property of the receptors.

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Accession: 010155588

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PMID: 11046098


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