Abstract
These studies examined adrenergic reactivity of mesenteric arteries and veins from deoxycorticosterone acetate-salt (DOCA-salt) hypertensive and sham control mice. We measured constrictions in unpressurized arteries and veins by monitoring vessel diameter using computer-assisted video micros-copy in vitro. Veins were more sensitive than arteries to the constricting effects of norepinephrine (NE) and phenylephrine (PE), but the α2-agonists clonidine and UK 14,304 [5-bromo-6-(2-imidazolin-2-yl-amino)-quinoxaline] did not constrict arteries or veins. Reactivity was not altered in arteries or veins from DOCA-salt mice. We next investigated the mechanism of increased venous reactivity to NE and PE by studying desensitization to maximum concentrations of NE and PE. Sham arteries desensitized to NE and PE more than DOCA-salt arteries, whereas DOCA-salt and sham veins maintained 80% of the initial NE and PE constriction. To determine whether the increased reactivity and resistance to desensitization in veins was due to a greater α-adrenoceptor reserve, vessels were incubated with the alkylating agent phenoxybenzamine (PBZ; 0.3, 3, 10, and 30 nM). The NE-elicited initial constriction was reduced by PBZ (3, 10, and 30 nM) in sham but only by PBZ (30 nM) in DOCA-salt veins. All doses of PBZ blocked NE responses in sham and DOCA-salt arteries. These data suggest that mesenteric veins express more α1-adrenoceptors than arteries, accounting for greater reactivity and resistance to desensitization compared with arteries.
Footnotes
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This work was supported by National Institutes of Health Minority Student Predoctoral Fellowship HL072732-01 (to A.A.P.) and by National Institutes of Health Grant HL63973 (to G.D.F. and J.J.G.)
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DOI: 10.1124/jpet.103.056184.
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ABBREVIATIONS: SNS, sympathetic nervous system; NE, norepinephrine; α1, α-1; DOCA, deoxycorticosterone acetate; PE, phenylephrine; PBZ, phenoxybenzamine; CO, cardiac output; MCFP, mean circulatory filling pressure; TPR, total peripheral vascular resistance; UK 14,304, 5-bromo-6-(2-imidazolin-2-yl-amino)-quinoxaline.
- Received June 25, 2003.
- Accepted September 30, 2003.
- The American Society for Pharmacology and Experimental Therapeutics
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