Stress susceptibility as a determinant of the response to adrenergic stimuli in mesenteric resistance arteries of the rat.
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.
Smits
Bart W
BW
Department of Pharmacology-Toxicology, University Medical Center Nijmegen, Nijmegen, the Netherlands.
Siero
Helene L M
HL
Ellenbroek
Bart A
BA
Riksen
Niels P
NP
Cools
Alexander R
AR
Borggreven
Joop M P M
JM
Rongen
Gerard A
GA
Russel
Frans G M
FG
Smits
Paul
P
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
D018491:Dopamine Agonists; D011941:Receptors, Adrenergic; D014662:Vasoconstrictor Agents; D010656:Phenylephrine; D001058:Apomorphine