Vol. 295, Issue 2, 627-633, November 2000

An _1A/_1L-Adrenoceptor Mediates Contraction of Canine Subcutaneous Resistance Arteries¹

Sally Anne Argyle and John Christie McGrath

Autonomic Physiology Unit, Division of Neuroscience and Biomedical Systems, Institute of Biomedical & Life Sciences, University of Glasgow, Glasgow, Scotland, United Kingdom

To determine the characteristics of the 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 ₁-adrenoceptor subtypes, were assessed in the presence of cocaine (3 µM), corticosterone (30 µM), and propranolol (1 µM). The rank order of agonist potency (pEC₅₀ ± 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 _1D-adrenoceptor and most consistent with an _1A-adrenoceptor response. This is supported by the low affinity for the _1D-selective antagonist BMY 7378 (pK_B 6.51 ± 0.47). The low pA₂ values for prazosin (8.36) and HV723 (8.81), by definition, indicate the involvement of the putative _1L-adrenoceptor, a hypothesis supported by the pA₂ values for WB4101 (8.42) and 5-methyl-urapidil (8.08). Pre-exposure to 1 µM CEC had little effect, whereas 100 µM CEC reduced the maximum contraction but not the sensitivity to norepinephrine. This low sensitivity to CEC argues against the presence of the _1B-adrenoceptor. We conclude that, by current definitions, an _1A-/_1L-adrenoceptor causes contraction of these vessels. This does not support the concept that selectivity for the _1A-adrenoceptor is the basis for the effectiveness of some -blockers in some tissues, such as prostate, but not in other tissues such as blood vessels. Rather, the generally low potency of -blockers in some tissues may be due to a tissue-specific property of the receptors.