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

Abstract:

:To determine whether the vasoconstriction evoked by A1-adenosine receptor stimulation in the skin circulation caused the 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 microns) 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 microM] or prazosin [10 microM]), serotonin (methysergide [11 microM]), angiotensin II (saralasin [0.11 microM]), thromboxane (SK&F 88046 [13 microM]), or leukotrienes (SK&F 102922 [2.1 microM]). The vasoconstriction evoked by 2 nM CHA was attenuated by a subthreshold concentration (1 nM) of norepinephrine, whereas the vasoconstriction evoked by 0.1-1 microM 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 microM) 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 alpha-adrenergic and A1-adenosinergic receptors.

journal_name

Circ Res

journal_title

Circulation research

authors

Proctor KG,Stojanov I

doi

10.1161/01.res.68.3.683

subject

Has Abstract

pub_date

1991-03-01 00:00:00

pages

683-8

issue

3

eissn

0009-7330

issn

1524-4571

journal_volume

68

pub_type

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