Stress susceptibility as a determinant of endothelium-dependent vascular reactivity in rat mesenteric arteries.
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.
Riksen
Niels P
NP
Departments of Pharmacology and Toxicology, University Medical Center Nijmegen, HB Nijmegen, The Netherlands.
Ellenbroek
Bart
B
Cools
Alexander R
AR
Siero
Helene
H
Rongen
Gerard A
GA
Smits
Bart W
BW
Russel
Frans G M
FG
Smits
Paul
P
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*
D009569:Nitric Oxide; D011451:Prostaglandin-Endoperoxide Synthases; D001058:Apomorphine