Direct vasoconstriction evoked by A1-adenosine receptor stimulation in the cutaneous microcirculation

K. G. Proctor, I. Stojanov

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Abstract

To determine whether the vasoconstriction evoked by A1-adenosine receptor stimulation in the skin circulation caused tbe release of other substances or whether A1 stimulation modulated the vasoconstriction evoked by other compounds, a potent A1-selective, synthetic agonist, cyclohexyladenosine (CHA), was topically applied simultaneously with several different vasoconstrictor agonists or antagonists. CHA was chosen instead of adenosine because the parent compound is metabolized quickly and also does not discriminate between A1 or A2 receptors. Blood flow was calculated from measurements of arteriolar diameter (40-60 μm) and red blood cell velocity using intravital videomicroscopy. Responses were recorded only in a steady state. The dose-related vasoconstriction evoked by CHA (ED50, 2.07 ± 0.80 nM; half-minimal response, 93 ± 1%) was not attenuated by antagonists to norepinephrine (phentolamine [11 μM] or prazosin [10 μM]), serotonin (methysergide [11 μM]), angiotensin II (saralasin [0.11 μM]), thromboxane (SK and F 88046 [13 μM]), or leukotrienes (SK and F 102922 [2.1 μM]). The vasoconstriction evoked by 2 nM CHA was attenuated by a subthreshold concentration (1 nM) of norepinepbrine, whereas the vasoconstriction evoked by 0.1-1 μM norepinephrine was attenuated by a threshold concentration (1 nM) of CHA. Higher concentrations (10-100 nM) of CHA had no additional inhibitory effect. In contrast, CHA had no effect on the vasoconstrictions evoked by angiotensin II (10 nM or 1 μM) or serotonin (100 or 500 nM). Therefore, it is unlikely that A1-receptor stimulation causes the release of norepinephrine, serotonin, angiotensin, thromboxane, or leukotrienes in the skin microcirculation. Because norepinephrine attenuated the vasoconstriction evoked by CHA while CHA attenuated that evoked by norepinephrine, there appears to be a negative interaction between α-adrenergic and A1-adenosinergic receptors.

Original languageEnglish (US)
Pages (from-to)683-688
Number of pages6
JournalCirculation research
Volume68
Issue number3
DOIs
StatePublished - Jan 1 1991

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Keywords

  • angiotensin
  • leukotriene
  • micr ocirculation
  • norepinephrine
  • serotonin
  • skin
  • thromboxane

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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