INCREASE BY ADRENALINE OR ANGIOTENSIN-II OF THE ACCUMULATION OF LOW-DENSITY-LIPOPROTEIN AND FIBRINOGEN BY AORTIC WALLS IN UNRESTRAINED CONSCIOUS RATS

1 Earlier experiments of ours with anaesthetized rabbits showed that i nfusions of catecholamines into the carotoid blood stream significantl y increased the uptake of radioiodinated low density lipoprotein (LDL) by the artery wall after as little as 2 h. This observation has now b een extended to much longer time periods, i.e., 6 days, and another sp ecies, viz. conscious and unrestrained rats; also to another presser a gent, angiotensin II, as well as to another plasma protein, fibrinogen . 2 Groups of rats were infused from subcutaneously implanted osmotic minipumps for 6 days. The infusions were either into a carotid artery or into the surrounding tissues, with essentially the same effects. Co ntrol animals were infused with saline, and test animals with either a drenaline or angiotensin II. The minipump concentration of adrenaline of 4-5 mu M, which gave blood concentrations of 25-41 nM, increased th e blood pressure significantly after 3 days. The minipump concentratio n of angiotensin II of 9.9 mg ml(-1) was chosen to produce similar inc reases in blood pressure. 3 Five days after starting the infusion, rat s were injected i.v. with either homologous or human LDL labelled with [I-125]-tyramine cellobiose (TC), or with [I-131]-TC labelled human f ibrinogen. Twenty-four hours later, the animals were killed and the ra dioactivities determined in the whole aorta. The labelled TC radioacti vities represent primarily metabolised protein (because TC is trapped intracellularly), but also include the fraction of intact, i.e., non-m etabolized protein in transit through the vessel wall. To determine th e contribution of the latter, in some experiments we injected double-l abelled [I-131]-[(TC)-T-125]-LDL only. These experiments showed that t he [I-131]-LDL counts representing protein in transit accounted for ap prox. 20% of the total (TC)-T-125 counts and that this percentage was not significantly affected by adrenaline or angiotensin II. Therefore, the bulk of the experiments was carried out with single labelled prot eins, using I-125 to label TC-LDL and I-131 to label TC-fibrinogen. In these experiments, the radioactivity of the arterial wall thus provid es a cumulative measure of the uptake and degradation of proteins. 4 A ortic wall radioactivities from rat and human LDL and from human fibri nogen were significantly increased by both agents. Adrenaline at 25-41 nM increased the radioactivities by 52 and 47% for rat and human LDL respectively, and by 31% for human fibrinogen; these differences were highly significant (P < 0.01). Angiotensin II at ca. 10 nM also increa sed the radioactivities significantly, by 21% for human LDL and by 109 % for human fibrinogen (P < 0.05). 5 The results suggest that the accu mulation of LDL and of fibrinogen by rat aorta is increased by adrenal ine or by angiotensin II at concentrations which raise the blood press ure progressively and significantly after 3 or 5 days respectively.