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.

Purification and characterization of human vascular plasminogen activator.

The vascular tree of the legs of human corpses was perfused with 0.15 M NaCl, and eluted with 2 M KSCN and finally with 0.15 M NaCl. The average total activity of human vascular plasminogen activator and protein eluted per leg was 29 800 Ploug units and 8.3 g respectively. Fibrin-Sepharose adsorbed the plasminogen activator activity, which could be eluted with 2 M KSCN. A small column containing from 0.5--1.9 ml of phenyl-Sepharose, normally coupled directly to the outlet of the fibrin-Sepharose column, adsorbed all the plasminogen activator activity. Elution of this hydrophobic matrix yielded a plasminogen activator preparation 17% pure judging from sodium dodecyl sulphate polyacrylamide gel electrophoresis. By this method human vascular plasminogen activator was found to have an Mr of 60 000. Upon reduction, two bands of Mr 30 000 and 31 000 were estimated. Human vascular plasminogen activator could be inhibited by diisopropylfluorophosphate. Isoelectric focusing yielded four major bands with the isoelectric points of 6.9, 7.4, 8.0 and 8.6. Human vascular plasminogen activator was found to be a relatively stable protein in purified form.

Possible mechanism of prostaglandin-induced renal vasoconstriction in the rat.

We studied the role of the renin-angiotensin system in the vasoconstrictor effect induced by prostaglandins (PG) on the renal microcirculation in 25 euvolemic Munich-Wistar rats. Infusions of subvasodepressor doses of PgE2 and PGI2 led to lower mean values for single nephron (SN) glomerular filtration rate (GFR), total kidney GFR, glomerular plasma flow rate, QA, and ultrafiltration coefficient (Kf) than were found in animals given vehicle alone (control group). On the other hand, the mean values for glomerular transcapillary hydraulic pressure difference, delta P, and total renal arteriolar resistance, RTA, tended to be higher in the experimental groups. The effects of PGI2 on the renal microcirculation were more pronounced than for PGE2. These increases in delta P and RTA and decreases in QA and Kf are typical of changes induced by angiotensin II (AII). To further explore this AII-like phenomenon, an infusion of saralasin, a competitive AII antagonist, was used. Indeed, when saralasin was infused together with either PGE 2 or PGI2 the previously noted effects on delta P, QA, RTA and Kf were largely abolished. Thus, saralasin transformed the renal action of PGE2 and PGI2 from vasoconstrictor (low QA, high RTA) to vasodilator (high QA and low RTA). Therefore, the effects of nonvasodepressor doses of PGE2 and PGI2 on the renal microcirculation appear to depend on an intermediate action of AII.

Characterization of post-junctional alpha-adrenoceptors in the rat isolated perfused femoral artery.

A comparison was made of contractile responses to alpha-adrenoceptor agonists in the rat aorta and in the rat isolated perfused femoral artery. Dose-response curves were constructed to noradrenaline (alpha 1/alpha 2), methoxamine (alpha 1-selective) and B-HT 920 (alpha 2-selective). Methoxamine behaved as a full agonist in both tissues as compared with noradrenaline, while B-HT 920 was only a partial agonist in the aorta and produced small responses in the femoral artery preparation which were not dose-dependent. pA2 or -log KB values were calculated for prazosin and idazoxan against noradrenaline and methoxamine. Similar -log KB values for prazosin against both agonists were obtained in both tissues, while idazoxan was approximately ten times more potent in the femoral artery preparation than in the aorta. These results suggest that the aorta contains a single population of alpha 1-adrenoceptors, while the perfused femoral artery preparation contains predominantly alpha 1-adrenoceptors but also a small population of alpha 2-adrenoceptors.

Plasma concentrations of 6-keto-prostaglandin F1 alpha in patients with hypertension, cerebrovascular disease or Takayasu's arteritis.

The peripheral venous plasma levels of 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) were determined by radioimmunoassay in 23 control subjects, 14 patients with essential hypertension, 19 patients with cerebrovascular disease (CVD) not taking aspirin, 12 patients with DVD taking aspirin, and 12 patients with Takayasu's arteritis. There was no significant difference in 6-keto-PGF1 alpha levels between the control subjects and hypertensive patients. In CVD patients and patients with Takayasu's arteritis, the plasma 6-keto-PGF1 alpha levels were significantly lower than those in control subjects. The internal jugular venous and femoral arterial plasma levels of 6-keto-PGF1 alpha and thromboxane B2 (TxB2) were measured in 10 CVD patients not taking aspirin. The patients with occlusive lesions of major arteries exhibited higher TxB2/6-keto-PGF1 alpha ratios in the internal jugular venous plasma.

Restriction of placental growth in sheep enhances placental metabolism of fetal beta-endorphin-like immunoreactivity.

The opioid polypeptide beta-endorphin is present in fetal blood but it is not clear whether its source is the fetus or the placenta. We therefore measured beta-endorphin in extracts of fetal femoral arterial and umbilical venous blood plasma in sheep by radioimmunoassay to determine whether the fetus or the placenta is the major source of beta-endorphin in the fetal circulation. Chromatographic analysis of extracts of fetal arterial plasma showed that beta-lipotropin and other precursors of beta-endorphin made only a minor contribution to the immunoreactivity detected. Concentrations of immunoreactive beta-endorphin were higher in the femoral artery than in the umbilical vein in fetal sheep between 113 and 128 days of pregnancy. Therefore the placenta removes beta-endorphin or a closely related polypeptide of fetal origin from the umbilical circulation in sheep at this stage of gestation. Acute hypoxaemia and hypoglycaemia increase the concentrations of immunoassayable beta-endorphin in blood plasma of adult and fetal sheep, but little is known about the effects of chronic hypoxaemia or hypoglycaemia on the circulating levels of beta-endorphin and related polypeptides in the fetus. Therefore we also measured immunoreactive beta-endorphin in blood plasma from fetal sheep in which growth retardation in association with restricted placental growth was produced by removal of endometrial caruncles before mating. Intra-uterine growth retardation was accompanied by chronic hypoglycaemia and chronic hypoxaemia in the fetuses. This was not associated with higher concentrations of beta-endorphin-like immunoreactivity in fetal arterial or umbilical venous plasma, but was accompanied by significantly increased placental extraction of fetal immunoreactive beta-endorphin from the umbilical circulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Heterogeneity of desmin, the muscle-type intermediate filament protein, in blood vessels and astrocytes.

Monoclonal antibodies were isolated from mice immunized with chicken gizzard desmin. Antibodies reacting with desmin on immunoblots and selectively decorating chicken and rat intestinal smooth muscle as well as the Z-line in striated muscle, were selected for this study. Based on their staining pattern on cryostat sections of chicken and rat cerebellum, spleen, kidney, aorta and femoral artery, monoclonal supernatants could be divided in three groups: (i) antibodies decorating astrocytes and vascular smooth muscle; (ii) antibodies decorating only vascular smooth muscle; (iii) antibodies decorating only astrocytes. Antibodies in group (i) and (iii) also stained GFA-negative Bergmann glia in chicken cerebellum. It is proposed that desmin may vary depending on the histological localization.

Activation of the human terminal complement pathway in atherosclerosis.

The presence of the terminal C5b-9 complement complex in tissues indicates that complement activation has occurred in situ with subsequent membrane damage, tissue injury, and inflammatory response mediation. The terminal C5b-9 neoantigens of the complement system, S protein C3c, C3d, and apolipoprotein B deposits were localized in 20 aortic fibrous plaques, 12 aortic intimal thickenings, 8 aortic fatty streak intimae, 14 coronary fibrous plaques, 5 coronary intimal thickenings, and 8 femoral fibrous plaques, using an indirect and double-staining immunoperoxidase technique. The specific granular deposits were present from the early to the advanced stages of atherosclerosis in relation to the degree of fibrosis and necrosis. The different double-staining localization of C5b-9 and S protein may suggest local assembly of the complex as a consequence of complement activation and may sustain its role in the chronic progression of atherosclerosis.

Arterial fibrous proteins in cynomolgus monkeys after atherogenic and regression diets.

Fibrous proteins were measured in five arterial beds in adult cynomolgus monkeys after administration of atherogenic and regression regimens. Atherosclerosis was induced by feeding the monkeys a hypercholesterolemic diet containing 1.2% cholesterol for 17 months. A low-fat, cholesterol-free regression diet was then given for 60 days, 200 days, and 20 months. In atherosclerosis, collagen concentration (mg/g dry weight) and collagen content (mg/cm length of artery) both increased. At 200 days of regression the collagen concentration, but not the collagen content, was higher than it was in atherosclerosis. In late regression (20 months), the collagen content was lower than it was in atherosclerosis, although in the five arterial beds considered together the collagen concentration was not significantly lower. Both the elastin concentration and the elastin content rose in atherosclerosis and decreased in regression. These mass data suggest that fibrous proteins are lost from the arterial wall during a regression regimen. Correlative evidence suggests that younger intimal fibers may be chiefly susceptible to fibrolytic activity, leaving dense intimal scars characteristic of regressed arteries.

Nuclear magnetic resonance imaging of atherosclerotic disease.

Nuclear magnetic resonance (NMR) images of 93 patients undergoing studies of the abdomen and pelvis were studied for evidence of lesions of the aorta and the iliac and femoral arteries; atherosclerotic lesions were present in 13 of them. The lesions consisted of eccentric and concentric mural thickening with luminal narrowing and discrete plaques protruding into the vessel lumen. This appearance was distinctly different from the morphology of the internal vessel surface and uniformly thin vessel wall in normal patients and volunteers under the age of 30 years. Intraluminal flow signals observed in atherosclerotic and nonatherosclerotic subjects could be distinguished from mural lesions because of their lack of contiguity with the vessel wall and variation in appearance on multiple images obtained with the first and second spin echo. This initial experience suggests a potential role for NMR in the noninvasive imaging of atherosclerotic lesions. The natural contrast between flowing blood and the vessel wall indicates a distinct advantage of NMR for vascular imaging.