Venning M G, De la Lande I S, Morris R G
Department of Clinical and Experimental Pharmacology, University of Adelaide, Australia.
Blood Vessels. 1988;25(4):185-98. doi: 10.1159/000158731.
(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.
(1) 研究了利血平预处理家兔动脉中外腔和内腔3H-去甲肾上腺素（3H-NA；0.18 μmol/L）的代谢情况。动脉在含钙培养基中进行灌注：(a) 无哌唑嗪时，以使血管收缩；(b) 有哌唑嗪时；(c) 内腔压力较高（110 mmHg；存在哌唑嗪）时，以使血管扩张。(2) 外腔NA的收缩活性极弱，哌唑嗪的拮抗作用与代谢产物生成的变化无关。扩张伴随的唯一变化是3,4-二羟基苯乙二醇（DOPEG）生成量小幅增加（24%）。(3) 内腔NA的收缩活性比外腔NA强得多。哌唑嗪对收缩的拮抗作用伴随DOPEG生成量增加5倍，去甲变肾上腺素（NMN）生成量增加2倍。扩张使DOPEG生成量进一步增加3倍，但对NMN生成影响不大。(4) 由于DOPEG源于神经元，因此推测上述第(3)点中DOPEG生成的变化反映了内腔NA扩散到交感神经末梢区域的速率变化。支持这一推测的依据是：(a) 当DOPEG生成量与决定NA扩散速率的血管尺寸相关而非与血管质量相关时，扩张无影响；(b) 收缩和扩张对内腔14C-山梨醇跨动脉壁扩散速率的影响与其对DOPEG生成的影响平行。(5) 第(3)点中收缩对NMN生成的影响归因于收缩的平滑肌中摄取2（NMN生成所依赖）减少，同时NMN生成和收缩活性均倾向于定位于血管壁最靠近NA进入表面的区域。(6) 估算了14C-山梨醇的扩散系数。估算结果表明：(a) 血管尺寸变化是扩散速率的主要决定因素；(b) 血管收缩时扩散率降低；(c) 当内腔压力较高使血管扩张时，内腔介质可能会大量流入血管壁。
