Differential contributions of alpha-1 and alpha-2 adrenoceptors to vasoconstriction in mesenteric arteries and veins of normal and hypertensive mice.
Mesenteric veins are more sensitive than arteries to the constrictor effects of sympathetic nerve stimulation and alpha-adrenergic receptor agonists. In the present study, we tested the hypothesis that alpha(2)-adrenergic receptors (alpha(2)-ARs) contribute to in vitro agonist-induced constriction in veins but not arteries and that alpha(2)-AR function is down-regulated in mesenteric arteries and veins in deoxycorticosterone acetate-salt (DOCA-salt) hypertension. Norepinephrine (NE) concentration-response curves were similar in SHAM and DOCA-salt arteries and veins indicating that adrenergic reactivity of mesenteric blood vessels is not altered in murine DOCA-salt hypertension in vitro. Veins were 30-fold more sensitive to NE than arteries. The alpha(1)-AR antagonist, prazosin (0.003-0.3 microM), produced concentration-dependent rightward shifts of the NE concentration-response curves in arteries but not veins. The alpha(2)-AR agonists, clonidine and UK-14,304, did not constrict arteries or veins in the absence or presence of indomethacin (10 microM) and nitro-L-arginine (NLA; 100 microM). The alpha(2)-AR antagonists, yohimbine (0.003-0.3 microM) and rauwolscine (0.1 microM) did not affect NE responses in SHAM or DOCA-salt arteries but antagonized NE responses in veins. These data indicate that there are different alpha-AR contractile mechanisms in murine mesenteric arteries and veins. Alpha(1)-ARs, but not alpha(2)-ARs, mediate direct contractile responses in arteries and veins while alpha(2)-ARs contribute indirectly to NE-induced constrictions in veins but not arteries in vitro. There may be direct protein-protein interactions between alpha(1)- and alpha(2)-ARs or between their signaling pathways in veins. This contribution of alpha(2)-ARs may account for the greater sensitivity of veins compared to arteries to the contractile effects of NE.
Pérez-Rivera
Alex A
AA
Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI 48824, USA.
Hlavacova
Alexandra
A
Rosario-Colón
Leonardo A
LA
Fink
Gregory D
GD
Galligan
James J
JJ
D018674:Adrenergic Antagonists / Q000494:pharmacology; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D003900:Desoxycorticosterone; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006973:Hypertension / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D008642:Mesenteric Veins / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009638:Norepinephrine / Q000494:pharmacology; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects / Q000378:metabolism*; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects / Q000378:metabolism*; D012965:Sodium Chloride; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D018674:Adrenergic Antagonists; D000316:Adrenergic alpha-Agonists; D018340:Receptors, Adrenergic, alpha-1; D018341:Receptors, Adrenergic, alpha-2; D014662:Vasoconstrictor Agents; D003900:Desoxycorticosterone; D012965:Sodium Chloride; D009638:Norepinephrine