Vanadate-evoked relaxation of the perfused rat mesenteric vascular bed.
Sodium orthovanadate (SOV) can contract smooth muscle; however, little is known about its effect on the vascular endothelium. We compared the vasorelaxant effects of acetylcholine (ACh) and SOV in the preconstricted, isolated perfused mesenteric vascular bed (MVB) of Sprague-Dawley rats. The maximal relaxation response evoked by SOV (40-45%) was lower than ACh (92-94%) but the IC50 values were similar. At concentrations > 1 mM, SOV elevated the basal tone. Endothelial denudation resulted in a substantial reduction of relaxation responses to both agents, whereas either nitric oxide synthase (NOS) inhibitors or high KCl partially reduced the responses. A combination of NOS inhibitors along with either a calcium-activated potassium channel (KCa) blocker, tetrabutylammonium (TBA), or high KCI inhibited the responses to a similar extent as endothelium denudation. Neither clotrimazole nor TBA attenuated ACh responses; however, maximal responses to SOV in the presence of TBA or clotrimazole were reduced. Indomethacin had no effect on responses to either agonists. These results indicate that like ACh, SOV-mediated vasorelaxation of the MVB involves recruitment of both endothelial derived hyperpolarizing factor (EDHF) and endothelial derived nitric oxide (NO) and not vasodilator eicosanoids. As the relaxation to SOV was dose-dependent at a low concentration range, it is likely that vanadate is involved in the regulation of total peripheral resistance.
Misurski
D
D
Department of Pharmacology, College of Medicine, University of Saskatchewan, Saskatoon, Canada.
Tatchum-Talom
R
R
McNeill
J R
JR
Gopalakrishnan
V
V
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D066298:In Vitro Techniques; D008643:Mesentery / Q000098:blood supply*; D008729:Methoxamine / Q000494:pharmacology; D009126:Muscle Relaxation / Q000187:drug effects; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D014638:Vanadates / Q000494:pharmacology*
D014638:Vanadates; D008729:Methoxamine; D000109:Acetylcholine