Pig Thoracic Aorta Research Articles

Effects of capsaicin on vascular smooth muscle

Acute administration of capsaicin in vitro produced either vascular smooth muscle contraction (cat middle cerebral artery) or smooth muscle relaxation (guinea pig carotid artery and thoracic aorta). Prior in vivo treatment with capsaicin abolished the relaxation response of guinea pig vessels to acute capsaicin. Instead a contractile response was seen after chronic capsaicin treatment, suggesting that the relaxation response produced by capsaicin is due to release of a vasodilator substance. Substance P caused relaxation in both cat cerebral arteries and the guinea pig thoracic aorta, an effect which was abolished or reduced by endothelial damage. However, responses to acute capsaicin were not altered by endothelial damage, suggesting that substance P does not mediate the relaxation response to acute capsaicin administration. Exposure to capsaicin in vitro did not affect the neurogenic vasodilator response of cat cerebral arteries and did not alter substance P levels. Therefore, it was concluded that the acute effect of capsaicin is composed of two components. A contractile response is most likely due to direct effects on vascular smooth muscle, while a relaxation response is attributed to release of an as yet unidentified bioactive substance distinct from substance P.

Contraction and cyclic AMP-related relaxation of the intimal and medial smooth muscle layers of pig thoracic aorta.

The contractile responses of an alpha-adrenoceptor agonist, phenylephrine, and of histamine were compared in the intimal and medial smooth muscle layers of the pig aortic arch. Further, the relaxant effects evoked by some compounds influencing the cyclic AMP system were compared in the two muscle layers, as well as their effects on the cyclic AMP content and phosphodiesterase activity. Phenylephrine and histamine induced contraction of the smooth muscle layers. The increase in tension was faster in the intimal than in the medial layer. The alpha-adrenoceptor agonist phenylephrine was a more potent contractile agent in the intimal than in the medial smooth muscle. With histamine, no significant difference in the dose-response curves between the two muscle layers was found. Histamine-contracted muscle preparations were relaxed in a dose-dependent manner by the phosphodiesterase-inhibiting compound 3-isobutyl-1-methylaxanthine (MIX) and by 8-bromo-cyclic AMP. The two substances were more potent relaxants in the medial than in the intimal smooth muscle layer. The content of cyclic AMP in the intimal and the medial smooth muscle was increased by MIX. Isoprenaline had no relaxing effect on the muscle preparations and did not change the content of cyclic AMP. There were no differences in the basal levels of cyclic AMP in the intima and media. Vmax of phosphodiesterase activities differed, however, between the two preparations. This study demonstrates that the intimal layer is characterized by a larger contractile responsiveness to phenylephrine and a lower relaxant response to compounds influencing the cyclic AMP-system than those of the medial layer.

Role of medial lamellar architecture in the pathogenesis of aortic aneurysms

The human abdominal aorta is particularly susceptible to the formation of aneurysms with atrophic walls. This aortic segment normally has fewer medial lamellar units than would be expected for a mammalian aorta of comparable diameter as well as far fewer medial vasa vasorum than would be expected for an aortic wall of comparable thickness. To test the hypothesis that ischemia and/or loss of normal lamellar architecture are predisposing factors for aneurysm formation, we used the pig thoracic aorta, which is furnished with 75 medial layers and vasa supplying the outer two thirds. Vasal blood flow was surgically ablated, and crushing injury was used to reduce the number of intact lamellar units. Mural ischemia alone resulted in necrosis of cells in the medial zone furnished by vasa but did not lead to aneurysmal dilatation, and all the fibrous tissue layers persisted during the 2-month observation period. Mechanical injury resulted in aneurysms in both ischemic and nonischemic aortic segments, but only if fewer than 40 intact lamellae remained and the average tension per lamellar unit exceeded three times the normal value of 1316 ± 202 dynes/cm (4543 ± 1624 for ischemic and 4087 ± 871 for nonischemic segments; p < 0.01 for each). We conclude that a critical reduction in the number of intact lamellar units results in aneurysmal dilatation. Protracted medial ischemia due to intimal plaque formation in the avascular abdominal aorta may eventually reduce the number of intact lamellae and favor the development of aneurysms.

Influence of anoxia and dinitrophenol on the phosphorylase a activity and the cyclic nucleotide content of smooth muscle.

The effect of anoxia or 2,4-dinitrophenol (DNP) on the phosphorylase activity and the cyclic AMP and the cyclic GMP content was studied in smooth muscle preparations. When the aerobic conditions were changed to anaerobic in experiments on bovine mesenteric artery, there was a significant increase in the activity of phosphorylase a during the first 60 min. We had observed a reduction of the glycogen content of the artery during this time period, which accounted for about 2/3 of the increase in lactate production (Pasteur effect). Under anaerobic conditions the content of cyclic AMP in the vessel was not changed, and the increase in phosphorylase a activity was not inhibited by a blockade of adrenergic beta-receptors. DNP, which like anoxia inhibits the mitochondrial production of ATP, increased the phosphorylase a activity to the same extent as anoxia. Anoxia and DNP also enhanced the activity of phosphorylase a in pig thoracic aorta and rabbit colon smooth muscle. In thoracic aorta both anoxia and DNP produced a more transient and smaller increase in the phosphorylase a activity than in the mesenteric artery. The Pasteur effect was also relatively smaller (100%) in thoracic aorta than in mesenteric artery (400%). It is suggested that an anoxic increase in the phosphorylase a activity participates in the Pasteur effect in smooth muscle.

Visualization of the 10-nm filament vimentin rings in vascular endothelial cells in situ: Close resemblance to vimentin cytoskeletons found in monolayers in vitro

Surface staining of the intact vascular endothelial cell layer lining the lumen of guinea pig thoracic aorta with antibodies to vimentin revealed that at least 70% of the cells contained intact perinuclear rings of 10-nm filaments. This correlated with the observations made on these cells in culture: 60–80% of the endothelial cells at confluence have complete perinuclear rings. By one- and two-dimensional gel electrophoresis and immunoprecipitation we confirmed that vimentin [17, 18] is the major constituent polypeptide of the 10-nm filaments in guinea pig endothelial cells. These results indicate that the vimentin [17] 10-nm filament cytoskeleton found in guinea pig endothelial cells in vitro is similar to the cytoskeleton found in situ.

Effects of normal stress on aorta surface stretching and permeability

Homogeneous segments of the ventral portion of pig thoracic aorta were incubated in specially constructed chambers to assess the effects of fluid pressure, in the absence of shearing stress, on surface stretching, and permeability to albumin. A linear relationship was established between pressure and surface area; and there was an exponential increase in radioactive albumin permeation as a function of pressure. A pressure increase from 0 to 240 mm Hg resulted in a 35% increase in surface area, whereas a pressure increase from 50 to 240 mm Hg resulted in a five-fold increase in albumin uptake by tissue segments. These results were compatible with the idea that increased stretching of tissue resulted in gaps between endothelial cells through which albumin was able to enter into the artery wall.

Influence of static and oscillatory pressure/strain on 131I-albumin uptake by the wall of the isolated pig thoracic aorta.

The uptake of 131I-albumin by the wall of the isolated pig thoracic aorta was investigated in vitro to achieve good control of the experimental conditions. The lumena of the arteries were perfused with a balanced salt solution (Hanks') containing the radioactively labelled albumin. Albumin flux was studied at three static intralumenal pressures, viz 6.7, 13.3 and 20 kPa (50, 100 and 150 mmHg) and uptake (normalised per unit dry tissue weight) was found to be approximately doubled on increasing the pressure from 6.7 to 20 kPa (50 to 150 mmHg). With a mean pressure of 6.7 kPa (50 mmHg) the uptake was studied in the presence of sinusoidal pressure oscillations of amplitude in the range 1.3 to 6.0 kPa (10 to 45 mmHg) at frequencies 1, 5 and 11 Hz. At each frequency the uptake was found to be dependent on the pressure amplitude. The dependence at 5 Hz was significantly stronger than at 1 Hz (P < 0.05) and although not significant there was a suggestion that the uptake was higher at 5 than 11 Hz. There was no significance and no suggestion of a difference at 1 and 11 Hz. The possible influence on uptake of the associated oscillatory wall shear component has been considered. The relevance of these findings to macromolecular transport and to the characteristic localisation of atheroma within the arterial tree is discussed.

Elastin as a rubber.

AbstractThe thermoelastic behavior of water solvated elastin has been investigated in simple tension, in the temperature range 0–70°C. Specimens purified from both the ox ligamentum nuchae and pig thoracic aorta have been studied. Force data obtained by cycling the temperature for various constant specimen lengths display a separated variable dependence of the form f = A(T)B(α), where T is absolute temperature and α the extension ratio. For ligament elastin B(α) is a linear function whereas for aortic elastin it is a nonlinear function. The applicability of the rubber elasticity theory to elastin has been tested by setting A(T) equal to the temperature‐dependent front factor for simple tension of a homogeneous rubber whilst B(α) is left undefined. In this way it has been possible to take into account the fibrous nonhomogeneity of the polymer, and also to avoid any inconsistency within the theory of attributing a dependence of the variable fe/f upon extension ratio. The behavior of both ligament and aortic elastin agrees well with the conclusion that the dominant deformation mechanism is entropy elastic, fe/f ≪ 1. The linearity of the load isotherm for ligament elastin permits a particularly simple experimental procedure using a single force‐temperature plot for one value of interclamp length. Using this procedure high precision has been obtainble, and the data shows a close adherence to the theory with fe/f = 0.1. The relationship between this result and current controversy over the molecular conformation of elastin is discussed.