title: Stress susceptibility as a determinant of the response to adrenergic stimuli in mesenteric resistance arteries of the rat.
abstract: Characterized by the behavioral response to apomorphine, two outbred lines of Wistar rats can be recognized with constitutionally determined high (apomorphine susceptible, APO-SUS) or low (apomorphine unsusceptible, APO-UNSUS) adrenal responses to similar environmental stress. Within the accumbens nucleus, the APO-SUS and APO-UNSUS rats differ in alpha -adrenergic receptor responsiveness. This study explored whether these differences in adrenergic receptor sensitivity also exist in mesenteric resistance arteries. A Mulvany myograph was used to study the vasomotor responses of isolated mesenteric resistance arteries to adrenergic receptor stimulation. Phenylephrine (alpha1-agonist)-induced vasoconstriction did not differ between the two lines (pEC : 5.8 +/- 0.05 microM versus 5.8 +/- 0.04 microM and Emax: 36 +/- 2 kPa versus 33 +/- 1 kPa for APO-SUS, n = 9, and APO-UNSUS, n = 11, respectively, p > 0.1). After precontraction with phenylephrine, salbutamol (beta -agonist)-induced relaxation was less in APO-SUS rats (pEC50 4.9 +/- 0.06 versus 5.3 +/- 0.06M for APO-SUS, n = 9, and APO-UNSUS, n = 7, respectively, p < 0.001). Likewise, clonidine (alpha2-agonist)-induced relaxation was reduced in APO-SUS rats (pEC50: 6.7 +/- 0.07 versus 7.0 +/- 0.04, for APO-SUS, n = 9, and APO-UNSUS, n = 8, respectively; p < 0.01). In conclusion, constitutionally determined high susceptibility to stress is accompanied by an impaired vasorelaxation to adrenergic stimuli whereas vasoconstriction is unaffected. An unopposed vasoconstrictor action of norepinephrine may place the APO-SUS rats at increased risk for the development of hypertension, insulin resistance, and atherosclerosis.
authors.affiliation: Department of Pharmacology-Toxicology, University Medical Center Nijmegen, Nijmegen, the Netherlands.
authors.forename: Bart W
authors.initials: BW
authors.lastname: Smits
authors.forename: Helene L M
authors.initials: HL
authors.lastname: Siero
authors.forename: Bart A
authors.initials: BA
authors.lastname: Ellenbroek
authors.forename: Niels P
authors.initials: NP
authors.lastname: Riksen
authors.forename: Alexander R
authors.initials: AR
authors.lastname: Cools
authors.forename: Joop M P M
authors.initials: JM
authors.lastname: Borggreven
authors.forename: Gerard A
authors.initials: GA
authors.lastname: Rongen
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 / Q000008:administration & dosage / Q000494:pharmacology*; D018491:Dopamine Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D011941:Receptors, Adrenergic / Q000187:drug effects*; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects
chemical_list: D018491:Dopamine Agonists; D011941:Receptors, Adrenergic; D014662:Vasoconstrictor Agents; D010656:Phenylephrine; D001058:Apomorphine