Vascular reactivity of mesenteric arteries and veins to endothelin-1 in a murine model of high blood pressure.
We characterized vascular reactivity to endothelin-1 (ET-1) in mesenteric vessels from DOCA-salt hypertensive and SHAM control mice and assessed the effect that endothelial-derived vasodilators have on ET-1-induced vasoconstriction. Changes in the diameter of unpressurized small mesenteric arteries and veins (100- to 300-microm outside diameter) were measured in vitro using computer-assisted video microscopy. Veins were more sensitive than arteries to the contractile effects of ET-1. There was a decrease in arterial maximal responses (E(max)) compared to veins, this effect was larger in DOCA-salt arteries. The selective ET(B) receptor agonist, sarafotoxin 6c (S6c), contracted DOCA-salt and SHAM veins but did not contract arteries. The ET(B) receptor antagonist, BQ-788 (100 nM), but not the ET(A) receptor antagonist, BQ-610 (100 nM), blocked S6c responses. BQ-610 partially inhibited responses to ET-1 in mesenteric veins from DOCA-salt and SHAM mice while BQ-788 did not affect responses to ET-1. Co-administration of both antagonists inhibited responses to ET-1 to a greater extent than BQ-610 alone suggesting a possible functional interaction between ET(A) and ET(B) receptors. Responses to ET-1 in mesenteric arteries were completely inhibited by BQ-610 while BQ-788 did not affect arterial responses. Nitric oxide synthase inhibition potentiated ET-1 responses in veins from SHAM but not DOCA-salt mice. There was a prominent role for ET-mediated nitric oxide release in DOCA-salt but not SHAM arteries. In summary, these studies showed a differential regulation of ET-1 contractile mechanisms between murine mesenteric arteries and veins.
Department of Pharmacology and Toxicology, Michigan State University, East Lansing, B 440 Life Sciences Building, East Lansing, MI 48824, USA. perezriv@msu.edu
Alex A
AA
Pérez-Rivera
Gregory D
GD
Fink
James J
JJ
Galligan
D000465:Algorithms; D000818:Animals; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D003900:Desoxycorticosterone; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects; D006973:Hypertension / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D007213:Indomethacin / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D008642:Mesenteric Veins / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D009206:Myocardium / Q000473:pathology; D009842:Oligopeptides / Q000494:pharmacology; D009929:Organ Size / Q000187:drug effects; D010880:Piperidines / Q000494:pharmacology; D017466:Receptors, Endothelin / Q000819:agonists; D014665:Vasodilator Agents / Q000494:pharmacology; D014757:Viper Venoms / Q000494:pharmacology
D016861:Cyclooxygenase Inhibitors; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D009842:Oligopeptides; D010880:Piperidines; D017466:Receptors, Endothelin; D014665:Vasodilator Agents; D014757:Viper Venoms; C057354:sarafotoxins s6; C087220:BQ 610; D003900:Desoxycorticosterone; C086539:BQ 788; D007213:Indomethacin