Responses to noradrenaline in human subcutaneous resistance arteries are mediated by both alpha 1- and alpha 2-adrenoceptors.
1. In vitro experiments in a microvascular myograph were designed to characterize postjunctional alpha-adrenoceptors of human subcutaneous resistance arteries (normalised internal diameter 143-313 microns). 2. Both the alpha 1-selective agonist phenylephrine in the presence of 0.3 microM yohimbine and the alpha 2-selective agonist B-HT 933 in the presence of 0.3 microM prazosin elicited prominent and concentration-dependent contractions. The maximum response to phenylephrine and B-HT 933 was not different from the response to high K physiological salt solution (125 mM K+), and the pD2 values (-log EC50) were 5.90 and 6.11, respectively. 3. In the presence of the alpha 2-selective antagonist yohimbine (0.3 microM), the alpha 1-selective antagonist prazosin competitively antagonised the responses to phenylephrine; the pA2 of prazosin for the receptor which mediated the response to phenylephrine was 8.41. 4. Blockade of either alpha 2-adrenoceptors with 0.1 microM yohimbine or alpha 1-adrenoceptors with 0.1 microM prazosin caused shifts to the right of the noradrenaline concentration-response curves and the shifts in pD2 were 0.69 and 0.61, respectively. The combination of the two antagonists at the above-mentioned concentrations caused a marked, parallel shift to the right of the noradrenaline concentration-response curve, the shift of the pD2 was 2.68. 5. These results suggest that activation of both alpha 1- and alpha 2-adrenoceptors produces contractions in human subcutaneous resistance arteries, and that responses to noradrenaline in these vessels are mediated by both alpha-adrenoceptor subtypes.
Nielsen
H
H
Institute of Pharmacology & Danish Biomembrane Research Centre, University of Aarhus, Denmark.
Mortensen
F V
FV
Mulvany
M J
MJ
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000328:Adult; D000368:Aged; D001158:Arteries / Q000187:drug effects; D001381:Azepines / Q000494:pharmacology; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009638:Norepinephrine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D011224:Prazosin / Q000378:metabolism / Q000494:pharmacology; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D015016:Yohimbine / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D001381:Azepines; D011942:Receptors, Adrenergic, alpha; D015016:Yohimbine; C015603:azepexole; D009638:Norepinephrine; D011224:Prazosin