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1-adrenoceptor-mediated constriction of
arterioles
Department of Physiology and Biophysics, University of Louisville School of Medicine, Louisville, Kentucky 40292
We examined endothelial modulation
of norepinephrine (NE)-mediated constriction in isolated, cannulated,
first-order arterioles from skeletal muscle of rats. Acute arteriolar
constrictor responses to NE (10
9 to 10
7 M)
were significantly (P < 0.05) enhanced after either
endothelial denudation or inhibition of nitric oxide synthase with
NG-monomethyl-L-arginine
(10
4 M, 30 min). In contrast, arteriolar constrictions to
NE were not different after treatment with either the cyclooxygenase
inhibitor diclofenac (10
6 M, 30 min) or the
K+-channel blocker tetrabutylammonium (5 × 10
5 M, 30 min). We also measured arteriolar responses to
the vasoconstrictor PGF2
; responses were not altered by
any of the experimental treatments, which indicates that this
phenomenon is not ubiquitous to all vasoconstricting agents.
Mechanistically, we examined vascular smooth muscle (VSM) and
endothelial cell calcium. Both NE and PGF2
significantly
increased VSM cell calcium measurements; however, endothelial cell
calcium was significantly increased with NE or phenylephrine (an
1-adrenergic agonist) but not with PGF2
or UK-14304 (an
2-adrenergic agonist). Together these findings suggest that in rat cremaster first-order arterioles, NE
stimulates an increase in VSM calcium via adrenergic receptors with
subsequent increase in endothelial cell calcium, possibly via
stimulation of
1-adrenergic receptors on the arteriolar
endothelium. The burst in endothelial cell calcium may then lead to the
production of nitric oxide, which diffuses to the VSM, attenuates
constriction, and maintains at least some minimal level of blood flow.
norepinephrine; vascular smooth muscle; endothelial cell calcium; protstglandin F2
; phenylephrine; UK-14304
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