Responsiveness to noradrenaline in aorta from wild-type, nitric oxide synthase-2, nitric oxide synthase-3 and alpha2A/D-adrenoceptor knockout mice.
We have investigated the responsiveness of mouse aorta to noradrenaline (10 microM). In wild-type mice, noradrenaline produced an initial peak contraction (3.35+/-0.28 mN) and a significantly smaller plateau response (2.15+/-0.41 mN). The contractions were similar in aorta from nitric oxide synthase-2 (NOS-2) knockout mice. In vessels from NOS-3 knockout mice, noradrenaline contractions consisted of an early steeply rising phase with a later shallow rising phase to a maximum (10.21+/-0.84 mN), which was significantly greater than in wild-type and NOS-2 knockout mice, and resembled the contraction to phenylephrine (10 microM) in wild-type. In alpha(2A/D)-adrenoceptor knockout mice, the noradrenaline maximum was significantly smaller than in NOS-3 knockout but significantly larger than in wild-type. Following N(G)-nitro-L-arginine methyl ester (L-NAME, 10 microM), responses in wild-type and alpha(2A/D)-adrenoceptor knockout were as in NOS-3 knockout mice. The alpha(2D)-adrenoceptor antagonist BRL 44408 (2-((4,5-dihydro-1H-imidazole-2-yl)methyl)-2,3-di-hydro-1-methyl-1H-isoindole maleate; 1 microM) increased noradrenaline-induced contractions and the alpha(2)-adrenoceptor agonist xylazine reduced Prostaglandin F(2alpha)-induced contractions, in wild-type but not NOS-3 knockout. Contractions to noradrenaline in mouse aorta are modulated by NOS-3 and part of the effect involves activation of alpha(2A/D)-adrenoceptors.
Vandeputte
Catherine
C
Department of Physiology, Royal College of Surgeons in Ireland, 2, Dublin, Ireland.
Aiden McCormick
P
P
Docherty
James R
JR
D000316:Adrenergic alpha-Agonists / Q000097:blood / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000502:physiology; D004730:Endothelium, Vascular / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D054833:Isoindoles; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000172:deficiency / Q000235:genetics*; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D009638:Norepinephrine / Q000097:blood / Q000494:pharmacology*; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D014991:Xylazine / Q000494:pharmacology
C547769:Adra2a protein, mouse; D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D007093:Imidazoles; D007211:Indoles; D054833:Isoindoles; D018341:Receptors, Adrenergic, alpha-2; D014991:Xylazine; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496317:Nos2 protein, mouse; C496315:Nos3 protein, mouse; D019331:NG-Nitroarginine Methyl Ester; D009638:Norepinephrine; C072125:BRL 44408