Nitric oxide release during alpha1-adrenoceptor-mediated constriction of arterioles.
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 x 10(-5) M, 30 min). We also measured arteriolar responses to the vasoconstrictor PGF2alpha; 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 PGF2alpha significantly increased VSM cell calcium measurements; however, endothelial cell calcium was significantly increased with NE or phenylephrine (an alpha1-adrenergic agonist) but not with PGF2alpha or UK-14304 (an alpha2-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 alpha1-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.
Tuttle
J L
JL
Department of Physiology and Biophysics, University of Louisville School of Medicine, Louisville, Kentucky 40292, USA.
Falcone
J C
JC
D000818:Animals; D001160:Arterioles / Q000502:physiology*; D002118:Calcium / Q000502:physiology*; D004730:Endothelium, Vascular / Q000502:physiology; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018340:Receptors, Adrenergic, alpha-1 / Q000502:physiology*; D014661:Vasoconstriction / Q000502:physiology*
D018340:Receptors, Adrenergic, alpha-1; D009569:Nitric Oxide; D002118:Calcium