Vasorelaxation and hyperpolarisation of rat small mesenteric artery by the quaternary anion tetraphenylboron.
This study characterises the vasorelaxation and hyperpolarisation effects of the negatively charged quaternary compound tetraphenylboron (TPB) in the rat small mesenteric artery. Segments of rat small mesenteric artery were mounted in a myograph and vessel tone and membrane potential were measured simultaneously. In vessels pre-contracted with vasopressin (0.3-0.6 nM), U46619 (30-90 nM) or methoxamine (0.3-3 microM), TPB (0.1-100 microM) produced a marked endothelium-independent relaxation. However, vasorelaxation responses to TPB were abolished in tissues pre-contracted with K(+) (50 mM), and significantly inhibited by glibenclamide (glib, 10 microM). In the absence of tone, TPB (1-30 microM) caused a concentration-dependent membrane hyperpolarisation of rat mesenteric artery smooth muscle cells, which was not dependent on the endothelium, but sensitive to glibenclamide (10 microM). In methoxamine (0.3-3 microM) pre-contracted vessels, the relaxation response was associated with a marked hyperpolarisation, which was also sensitive to glibenclamide (10 microM), further inhibited by a combination of K(+) channel blockers (glib [10 microM], charybdotoxin [100 nM], apamin [100 nM], 4-aminopyridine [1 mM] and Ba(2+) [30 microM]) and abolished by 50 mM K(+). The results of this study show that TPB causes a vasorelaxation and hyperpolarisation response in the rat small mesenteric artery through a direct action on the vascular smooth muscle. TPB exerts its effects partially via the activation of K(ATP) channels, but also by another mechanism involving K(+)-dependent hyperpolarisation.
Favaloro
Joanne L
JL
Department of Pharmacology, Monash University, 3800 Clayton, Victoria, Australia. Joanne.Favaloro@med.monash.edu.au
McPherson
Grant A
GA
D000818:Animals; D002462:Cell Membrane / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials; D017537:Mesenteric Artery, Inferior / Q000187:drug effects* / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D011188:Potassium / Q000502:physiology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013775:Tetraphenylborate / Q000008:administration & dosage / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*
D026902:Potassium Channel Blockers; D015221:Potassium Channels; D014665:Vasodilator Agents; D013775:Tetraphenylborate; D011188:Potassium