title: Stress susceptibility as a determinant of endothelium-dependent vascular reactivity in rat mesenteric arteries.
abstract: In order to investigate the consequences of stress susceptibility on vascular function, the authors assessed the respective contributions of nitric oxide (NO), prostanoids, and endothelium-derived hyperpolarizing factor to the vascular tone in rats with a constitutionally determined high and low susceptibility to behavioral stressors. In mesenteric resistance arteries mounted in a small vessel myograph and precontracted with l-phenylephrine hydrochloride (phenylephrine), the NO-synthase inhibitor N omega-nitro-l-arginine (l-NOARG, 100 microM) elicited a smaller increase of vascular tone in apomorphine-susceptible (APO-SUS) rats (P < 0.01). Addition of indomethacin (10 microM), in the presence of l-NOARG, resulted in a smaller decrease of vascular tone in APO-SUS rats (P < 0.01). Although acetylcholine-induced relaxation in phenylephrine-precontracted arteries was not different (P > 0.1), the individual components contributing to this relaxation were. In arteries precontracted with 125 mM K+, and incubated with indomethacin, acetylcholine-induced relaxation was not significantly different (pEC(50) and E(max): P > 0.1). Sensitivity (pEC(50): P < 0.05) and maximum relaxation (E(max): P < 0.001) to sodium nitroprusside, in the presence of 125 mM K+, was more pronounced in APO-SUS rats. In phenylephrine-precontracted arteries, in the presence of l-NOARG and indomethacin, maximum relaxation to ACh was reduced in APO-SUS rats (E(max): P < 0.05). This study showed that in rats with a high susceptibility to stressors, the contribution of NO to vascular tone was decreased as was the ratio of vasoconstrictor and vasodilator cyclooxygenase products in alpha-adrenergic precontracted arteries. End-organ sensitivity to NO was greater in APO-SUS rats, possibly due to up-regulation. Moreover, the contribution of endothelium-derived hyperpolarizing factor to acetylcholine-induced vasodilation was reduced in APO-SUS rat arteries.
authors.affiliation: Departments of Pharmacology and Toxicology, University Medical Center Nijmegen, HB Nijmegen, The Netherlands.
authors.forename: Niels P
authors.initials: NP
authors.lastname: Riksen
authors.forename: Bart
authors.initials: B
authors.lastname: Ellenbroek
authors.forename: Alexander R
authors.initials: AR
authors.lastname: Cools
authors.forename: Helene
authors.initials: H
authors.lastname: Siero
authors.forename: Gerard A
authors.initials: GA
authors.lastname: Rongen
authors.forename: Bart W
authors.initials: BW
authors.lastname: Smits
authors.forename: Frans G M
authors.initials: FG
authors.lastname: Russel
authors.forename: Paul
authors.initials: P
authors.lastname: Smits
mesh_terms: D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013312:Stress, Physiological / Q000378:metabolism*; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
chemical_list: D009569:Nitric Oxide; D011451:Prostaglandin-Endoperoxide Synthases; D001058:Apomorphine