Arterial wall metabolism in experimental hypertension of coarctation of the aorta of short duration.

Coarctation of the mid-thoracic aorata was surgically produced in mongrel dogs which were sacrificed from 4-12 wk after the operation. As compared to the findings in control animals, the sodium, chloride, and water content of the hypetensive portion of the coarcted thoracic aorta was significantly elevated, whereas the electrolyte and water content of the relatively normotensive portion of the coarcted aorta was normal. The sodium, potassium, and water content of the pulmonary artery, skeletal muscle, and cardiac muscle of the coarcted dog was not altered. These observations suggest that an elevated arterial pressure may influence the electrolyte and water composition of the arteries. The arterial pressure also may influence the content and synthesis of acid mucopolysaccharides (MPS) in the arteries since the content of sulfated MPS and the incorporation of injected radiosulfate into sulfated MPS were significantly increased in the hypertensive portion of the coarcted thoracic aorta but were significantly reduced in the relatively normotensive ("hypotensive") portion of the coarcted aorta. The observed increase in MPS may have been a factor directly responsible for the increase in the sodium content of the hypertensive aorta since MPS can act as polyelectrolytes and bind cations. Although the arterial pressure may influence certain metabolic functions in the arteries, it did not appear to have a direct effect on the arterial lipids since the lipid content of the hypertensive and of the relatively normotensive portions of the coarcted aorta were comparable to the values found in the normal aorta.

Effects of three fat-enriched diets on the arterial pressure of rabbits.

Rabbits were fed diets enriched with proprietary edible fats for 5 weeks, raising the fat content of their diet from 4% to 23%. The diet enriched with animal fat caused a 13.5% rise in arterial pressure. The diet enriched with vegetable oil caused an 8.5% rise in arterial pressure. The diet enriched with butter caused an initial rise of 10% decreasing to 6% by the fifth week. Histological examination of the carotid and renal arteries, and aorta revealed no changes in connective tissue or lipid content as compared with those of control animals. It is concluded that changes in arterial pressure can occur after ingestion of excess dietary lipid, and that these changes are not confined to any class of lipid, or related to its properties as an atherosclerotic agent.

The biochemical composition of haemodynamically-stressed vascular tissue. Part 2. The concentrations of protein and connective tissue components in the salt extracts of experimental arteriovenous fistulae.

Arteriovenous fistulae were fashioned between the right external jugular vein and the right common carotid artery in seven experimental sheep, which were then grazed for periods up to 4.25 years. Since the morphological changes in the tissue resemble human atherosclerosis, some of the changes in the extractable protein components in this model were studied. In the experimental venous tissue there was a 1.5-2.5 fold increase in salt-soluble protein. The concentration of extractable collagen was 1.5 times higher in the salt extracts of the experimental veins. The concentration of elastin in the extracts from experimental venous tissue was higher than for the sham-operated veins but the experimental arteries yielded lower levels than the contralateral arteries.

Effect of vasoactive agents and applied stress on the albumin space of excised rabbit carotid arteries.

Experiments were undertaken on excised rabbit common carotid arteries to assess whether the distribution volume for radioactively labelled albumin is influenced by smooth muscle tone or externally applied stress. In arteries at relaxed length and zero transmural pressure, the distribution volume in the media was reduced by noradrenaline at concentrations exceeding 10(-9) M and increased by both sodium nitrite and isosorbide dinitrate at concentrations exceeding 10(-4) M. The distribution volume was lower in both the media and adventitia of segments at in vivo length pressurized with air to prevent convection through the wall, than in segments at relaxed length and zero transmural pressure. Noradrenaline decreased and sodium nitrite increased the medial distribution volume of the tracer in these air-pressurized segments. The vasoactive agents did not change the [51Cr]EDTA space in vessels at relaxed length and zero transmural pressure, although there were small alterations of medial water content. Transient conditions raise interpretative difficulties because of uncertainty about endothelial permeability and time-dependent changes of wall properties. The changes of the distribution volume for labelled albumin are thought to reflect changes in the properties of the interstitium.

Calcitonin gene-related peptide in cardiovascular tissues of the rat.

The distribution of calcitonin gene-related peptide immunoreactivity in the cardiovascular system of the rat was investigated by radioimmunoassay and immunocytochemistry. The nature of the immunoreactivity was studied by gel permeation and high performance liquid chromatography. Immunocytochemistry demonstrated the existence of calcitonin gene-related peptide-containing nerve fibres throughout the cardiovascular system. These were present in all regions of the heart, particularly in association with the coronary arteries, within the papillary muscles and within the sinoatrial and atrioventricular nodes. Calcitonin gene-related peptide-containing fibres were found mainly in the adventitia of the arteries and veins. Calcitonin gene-related peptide concentrations were high in major arteries and veins but comparatively low in the heart, aortic arch and thoracic aorta. Chromatography showed that approximately 70% of the total immunoreactivity was identical to synthetic calcitonin gene-related peptide. Calcitonin gene-related peptide concentrations in the blood vessels of rats treated neonatally with capsaicin were not found to be significantly different from those in control animals although capsaicin caused significant reductions of calcitonin gene-related peptide levels in certain other tissues. The results of this study suggest that calcitonin gene-related peptide-containing fibres are likely to be of importance in the innervation of vascular tissues and raise the possibility that these fibres are different in character from calcitonin gene-related peptide-containing fibres found in other tissues.

The plasminogen activator of the arterial wall.

The plasminogen activator in 645 specimens of various human arteries--thoracic, abdominal aorta, carotic, pulmonary, renal, basilar, coronary - was studied using Todd's histochemical method. 92 cadavers were used, 1--18 hours post mortem from subjects aged from 272 days to 83 years. 45 specimens of pulmonary, renal and splenic arteries were obtained during surgery. The greatest fibrinolytic activity was within the adventitia. Intima occasionally showed very little fibrinolytic activity, or none at all. No statistically significant differences in plasminogen activator activity were found between the various arteries examined. A statistically significant increase in fibrinolysis in adventitia of atherosclerotic arteries was established. No correlation was found between the fibrinolytic activity of the arteries and their alkaline phosphatase content. Some properties of the plasminogen activator of the arterial vessel wall were evaluated. Influence of storage, inactivation with epsilonaminocaproic acid and extracted with potassium thiocyanate was studied.

Study of isotonic contrast media in intravenous digital subtraction angiography.

Arterial enhancement obtained with isotonic contrast media in intravenous digital subtraction angiography was studied. Ten dogs were injected with ioxaglate, iopamidol, and ioxitalamate at equal iodine concentration and at concentrations corresponding to plasma osmolality. Three variables were studied: osmolality, injection rate, and iodine dose. Provided their iodine concentration is sufficient, isotonic contrast media appear as efficient as the corresponding hypertonic formulation, at equal iodine dose. Moreover, the use of isotonic ioxaglate allows a lower dose of iodine to be administered without significant reduction in peak arterial value.

Incorporation of labeled renin into the tissues of the rabbit.

Our previous work has shown that pure hog renin, when injected into one-kidney, one-clip hypertensive rabbits elicits not only antirenin antibodies but also antibodies to what appears to be an altered form of renin (antigen M). Antiantigen M stains the cytoplasm of smooth muscle cells and certain other cells in tissues of normal and hypertensive rabbits. We now report studies in which pure 125I hog and rabbit renin have been infused into hypertensive rabbits for seven-day periods and the tissues subsequently examined for nondegraded radioactive components. The concentration and the distribution of radioactivity found in different tissues of six rabbits that received hog renin and six that received rabbit renin showed enormous variation, for which there is no reasonable explanation. A very significant amount of radioactivity was found to be incorporated into a high molecular weight or insoluble form that may be antigen M. A major portion of the radioactivity has a molecular weight of about 40,000 and has been assumed to be unaltered 125I renin. In plasma there was a very high molecular weight radioactive component that was capable of binding to antirenin or antiantigen M antibodies to a limited degree. In addition there was a major component with a molecular weight of 68,000 that is not formed in vitro but is produced in vivo. It resembles prorenin in human plasma in that it does not adsorb on pepstatin-Sepharose and does adsorb on Cibacron Blue. However, it differs from prorenin in that it does not bind to antirenin antibodies nor can it be activated by trypsin.

In vitro 4 MHz NMR proton relaxation times and in vitro mechanical behavior at low extension of human common carotid arterial wall.

We investigated the influence of the biomechanical behavior of human common carotid arterial wall on the NMR proton relaxation times using a Bruker Minispec at 4 MHz. The study was limited to low extension in simple longitudinal elongation of the carotid wall (the maximum loading stretch ratio being 40%). Twenty-five carotid samples divided into 2 longitudinal strips were tested. The first strip was used to determine the nondimensional elastic parameter alpha according to the mechanical model of Fung. The second strip was used to measure the proton relaxation times. T1 value was 316.8 ms +/- 27.6 and T2 value was 59.9 ms +/- 6.8. A significant linear correlation was found between T1 and Ln alpha (p = 0.02). T1 and T2 were not correlated to the age but linearly correlated to the tissue water content (p less than 0.0001), however the age and alpha were not correlated to the tissue water content. These results may reflect the differences in the amount of water binding sites of the elastin which is involved in the elasticity of the carotid wall at low extension.

Origins of human atherosclerotic plaques. The role of altered gene expression.

The dramatic rise and equally dramatic fall in the mortality from coronary heart disease in the 20th century is only partly explained. This article reviews the development of our ideas concerning possible pathways other than lipids that might play a role in the development of human atherosclerosis alone or in combination with one or more of the usually considered risk factors. In some instances, such as that of cigarette smoking, the proposed concept regarding genetic alterations in vascular smooth muscle suggests a mechanism for development of at least some of the lesions. Recent studies have shown that an aberration in platelet-derived growth factor gene expression is unlikely to be a factor in proliferation of smooth-muscle cells. Aberrant expression of other oncogenes or some as yet unknown virus remain as possible explanations of some of the incidence of atherosclerosis and its consequent coronary heart disease.

The effects of epsilon aminocaproic acid on contractile properties and catecholamine content of rat carotid arteries.

The prevalent use of epsilon aminocaproic acid (EACA) to prevent rebleeding in the preoperative management of ruptured intracranial aneurysms raises the question of a relationship between this drug and cerebral vasospasm. The effects of EACA on the contractile properties of the rat common carotid artery were measured in vitro, and the effects of EACA on the catecholamine content of these arteries were determined qualitatively. When carotid artery segments from rats that had been infused with lactated Ringer's solution alone were incubated in the presence of 1 mM EACA, they exhibited a decrease in contractile activity brought about by the presence of either serotonin or norepinephrine, and an increase in contractile activity when potassium chloride was used. These changes were not witnessed if the arterial segments came from rats that had been infused with lactated Ringer's solution containing EACA. No effect of epsilon aminocaproic acid was found on the median effective dose values for each vasoconstrictor used. Fluorescence histochemistry showed no qualitative changes in the catecholamine content of carotid arteries following EACA treatment.

Isolation and characterization of salt-soluble cross-linked elastin from vascular tissue.

Fibrous elastin, a stable and important constituent of vascular tissue undergoes degenerative changes including fragmentation in atherosclerosis. The nature of the protein fragments produced during the in vivo degradation of elastin is largely unknown. From salt extracts of haemodynamically stressed tissue in sheep, polypeptides were isolated by hydrophobic interaction chromatography. These polypeptides coacervated and had amino acid compositions similar to those of in vitro solubilized elastins. The presence of the cross-links, desmosine and isodesmosine, in the isolated material indicates that the fragments originated from fibrous elastin and that cleavage of cross-links is not necessary for the solubilization of the fibre.

Ammonia toxicity in cattle. V. Ammonia concentration of lymph and portal, carotid and jugular blood after the ingestion of urea.

Four rumen-fistulated Holstein steers were fitted with cannulas for the collection of portal, jugular and carotid blood. In addition, the thoracic duct of one steer was cannulated for the collection of lymph. Steers were given .125, .25 or .5 g urea/kg body weight 16 hr after a previous feeding. Within 5 min after the administration of the .5-g dose, rumen ammonia increased from 9.7 to 32.0 mg/100 ml, rumen pH from 6.47 to 7.87; portal blood ammonia from 1.02 to 8.01 mg/100 ml, carotid blood ammonia from .18 to 1.17 mg/100 ml and jugular blood ammonia from .13 to .36 mg/100 ml. Lymph ammonia increased from .22 to .32 mg/100 ml within 15 minutes. The .125- and .25-g doses or urea produced proportionate changes. In a second experiment, three Jersey cows were given .5 g urea/kg body weight, and the rates at which urea appeared in carotid and jugular blood were determined. Only small amounts of urea appeared in carotid and jugular blood during the first 5 min after dosing, but the concentrations then increased slowly but progressively. We concluded that because carotid blood ammonia concentration increased so rapidly after dosing with urea, ammonia must leak past the liver, and it is therefore unlikely, that there is a liver threshold for ammonia which must be exceeded before ammonia will reach the carotid artery. The marked difference in ammonia concentrations in carotid and jugular blood suggests that the brain takes up ammonia rapidly. While some ammonia is absorbed via the lymph, and thus bypasses the liver, the lymph does not appear to be a major contributor of ammonia to carotid blood.

[Evaluation of two commercial bovine vascular heterografts (author's transl)]. / Evaluation de deux hétérogreffes bovines commerciales pour le remplacement vasculaire.

Two commercially available grafts made from chemically modified bovine carotif arteries, Artegraft (Surgikos Corp. U.S.A.) and Solcograft (Solco A.G. Switzerland), were evaluated. Preliminary evaluation indicates that these products compare favorably with other more common chemically treated grafts of biological origin. Morphological characteristics, inflammatory response and thrombogenic potential were measured. Their structure suggest that each of the processes conserve the collagen morphology of the media and the adventitia originally present in the precursor arteries. Test implantations in dogs reveal a tendency to undergo stenosis near the anastomoses within a few months. After six months of in-vivo function, these grafts are not invaded with the expected neo-formed cells and new collagen in their central portion; this process takes place only near the anastomoses.