The involvement of smooth muscle P2X receptors in the prolonged vasorelaxation response to purine nucleotides in the rat mesenteric arterial bed.
1. ATP and adenine dinucleotides can elicit three different types of vasomotor response in the rat mesenteric arterial bed; vasocontraction, rapid relaxation (which may be masked by contraction) and slow and prolonged vasorelaxation. Contraction is mediated by smooth muscle P2X receptors and rapid relaxation by endothelial P2Y receptors. The mechanism of prolonged relaxation is, however, controversial. 2. In the present study, bolus injection of doses of alpha,beta-methylene ATP (alpha,beta-meATP; 5 pmol - 0.5 micromol; P2X receptor agonist) in methoxamine-preconstricted rat isolated mesenteric arterial beds, mimicked the action of ATP, causing contraction (R(max) 76+/-9 mmHg) followed by prolonged relaxation (78+/-11%; t(1/2) 14.6+/-1.5 min). KCl also elicited a biphasic response (R(max) contraction 73+/-8 mmHg; R(max) prolonged relaxation 70+/-6%; t(1/2) 7.7+/-1.9 min). 3. P2X receptor desensitization caused by perfusion with alpha,beta-meATP (10 microM) abolished contraction and prolonged relaxation to doses of alpha,beta-meATP (50 nmol). Rapid relaxation (32+/-7%; t(1/2) 32+/-2 s) was revealed, which was abolished by removal of the endothelium using distilled water. 4. Sodium deoxycholate treatment blocked contractile and prolonged relaxation responses to alpha,beta-meATP, ATP and KCl, whilst distilled water treatment had no significant effect on either phase of the biphasic responses. 5. These data indicate that smooth muscle P2X receptors are involved in both phases of the biphasic response (contraction followed by prolonged relaxation) to purine nucleotides in the rat isolated mesenteric arterial bed. Caution should be applied when using sodium deoxycholate to remove the endothelium because of possible damage caused by the detergent to receptors and/or the vascular smooth muscle.
Ralevic
V
V
School of Biomedical Sciences, University of Nottingham Medical School, Queen's Medical Centre, Nottingham NG7 2UH, UK. vera.ralevic@nottingham.ac.uk
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D003840:Deoxycholic Acid / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology*; D011189:Potassium Chloride / Q000494:pharmacology; D011685:Purine Nucleotides / Q000494:pharmacology*; D058910:Purinergic P2 Receptor Agonists; D058919:Purinergic P2 Receptor Antagonists; D051381:Rats; D017208:Rats, Wistar; D018048:Receptors, Purinergic P2 / Q000502:physiology*; D012701:Serotonin / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology; D014867:Water / Q000494:pharmacology
D011685:Purine Nucleotides; D058910:Purinergic P2 Receptor Agonists; D058919:Purinergic P2 Receptor Antagonists; D018048:Receptors, Purinergic P2; D014662:Vasoconstrictor Agents; D003840:Deoxycholic Acid; D014867:Water; D012701:Serotonin; D011189:Potassium Chloride; D000255:Adenosine Triphosphate; C002630:alpha,beta-methyleneadenosine 5'-triphosphate