title: Metabolism of exogenous noradrenaline in constricted and in distended rabbit ear arteries.
abstract: (1) The metabolism of extraluminal and of intraluminal 3H-noradrenaline (3H-NA; 0.18 mumol/l) was examined in arteries from reserpine-pretreated rabbits. The arteries were perfused in Ca medium (a) in the absence of prazosin to permit constriction to occur, (b) in the presence of prazosin, and (c) at a high intraluminal pressure (110 mm Hg; prazosin present) in order to distend the vessel. (2) The constrictor activity of the extraluminal NA was extremely weak, and antagonism by prazosin was not associated with a change in metabolite formation. The only change accompanying distension was a small (24%) increase in 3,4-dihydroxyphenylethylene glycol (DOPEG) formation. (3) The constrictor activity of intraluminal NA was much stronger than that of extraluminal NA. Antagonism of constriction by prazosin was accompanied by a 5-fold increase in DOPEG formation and a 2-fold increase in normetanephrine (NMN) formation. Distension resulted in a further 3-fold increase in DOPEG formation, but had little effect on NMN formation. (4) Since DOPEG is neuronal in origin, it is suggested that the changes in DOPEG formation in point 3 above reflect changes in the rate at which the intraluminal NA diffuses into the region of the sympathetic nerve terminals. In support of this suggestion, (a) distension was without effect when DOPEG formation was related to the vascular dimensions which determine rate of diffusion of NA, instead of to vascular mass, and (b) effects of constriction and distension on the rate of diffusion of intraluminal 14C-sorbitol across the artery wall paralleled their effects on DOPEG formation. (5) The effects of constriction on NMN formation in point 3 are attributed to diminished uptake2 (on which NMN formation depends) in the contracted smooth muscle, in association with tendencies for both NMN formation, and contractile activity, to be localized to the region of the vessel wall closest to the surface of entry of the NA. (6) Diffusion coefficients of 14C-sorbitol were estimated. The estimates indicate that (a) the changes in vascular dimensions are the prime determinants of rates of diffusion, (b) diffusivity is decreased when the vessel constricts, and (c) there may be bulk flow of the intraluminal medium into the vessel wall when it is distended by a high intraluminal pressure.
authors.affiliation: Department of Clinical and Experimental Pharmacology, University of Adelaide, Australia.
authors.forename: M G
authors.initials: MG
authors.lastname: Venning
authors.forename: I S
authors.initials: IS
authors.lastname: De la Lande
authors.forename: R G
authors.initials: RG
authors.lastname: Morris
mesh_terms: D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D001692:Biological Transport / Q000187:drug effects; D004058:Diffusion; D004423:Ear / Q000098:blood supply*; D008734:Methoxyhydroxyphenylglycol / Q000031:analogs & derivatives / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism* / Q000494:pharmacology; D010477:Perfusion; D011224:Prazosin / Q000494:pharmacology; D011312:Pressure; D011817:Rabbits; D013012:Sorbitol / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000378:metabolism* / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D013012:Sorbitol; D008734:Methoxyhydroxyphenylglycol; C010117:3,4-dihydroxyphenylglycol; D009638:Norepinephrine; D011224:Prazosin