Nitric oxide release during alpha(1)-adrenoceptor-mediated constriction ofarterioles

We examined endothelial modulation of norepinephrine (NE)-mediated constric tion in isolated, cannulated, first-order arterioles from skeletal muscle o f rats. Acute arteriolar constrictor responses to NE (10(-9) to 10(-7) M) w ere significantly (P < 0.05) enhanced after either endothelial denudation o r inhibition of nitric oxide synthase with N-G-mono-methyl- L-arginine (10( -4) M, 30 min). In contrast, arteriolar constrictions to NE were not differ ent 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 PGF( 2<alpha>); responses were not altered by any of the experimental treatments , which indicates that this phenomenon is not ubiquitous to all vasoconstri cting agents. Mechanistically, we examined vascular smooth muscle (VSM) and endothelial cell calcium. Both NE and PGF2a significantly increased VSM ce ll calcium measurements; however, endothelial cell calcium was significantl y increased with NE or phenylephrine (an alpha (1)-adrenergic agonist) but not with PGF(2 alpha) or UK-14304 (an alpha (2)-adrenergic agonist). Togeth er these findings suggest that in rat cremaster first-order arterioles, NE stimulates an increase in VSM calcium via adrenergic receptors with subsequ ent increase in endothelial cell calcium, possibly via stimulation of alpha 1-adrenergic receptors on the arteriolar endothelium. The burst in endothel ial cell calcium may then lead to the production of nitric oxide, which dif fuses to the VSM, attenuates constriction, and maintains at least some mini mal level of blood flow.