Abel L. Robertson

Angiotensin II: Rapid Localization in Nuclei of Smooth and Cardiac Muscle

Five to ten nanograms of labeled angiotensin II rapidly injected in the left ventricle of adult rats was found to induce significant ultrastructural endothelial changes, resulting in net increases in number and size of pinocytotic vesicles as well as widening of intercellular spaces. This effect was followed by preferential localization of the compound in the nuclear zone of vascular and cardiac muscle cells. The selective cellular localization of angiotensin II suggests that this vasoactive agent or some of its metabolic fragments may have specific effects on nuclear function.

Effects of Angiotensin II and Some Analogues on Vascular Permeability in the Rabbit

Recent investigations in the rat have shown that endothelial cell contraction should be included among the multiple actions of angiotensin II (AII) in large arteries. In the current study, after intravenous injections (60 mg/kg) of the azo dye Evans blue, a segment of the rabbit abdominal aorta was isolated between temporary ligatures and injected with 1 × 10−10 g of AII diluted in Ringers solution. Diffuse increased permeability of the aortic endothelium occurred within 60 seconds only in areas exposed to AII. Although injections of Ringers solution alone produced no blueing, surface staining and scanning electron microscopy of the aortic endothelium after AII administration showed endothelial cell contraction, widening of the interendothelial junctions, and surface sudanophilia. Similar studies were carried out to determine changes in dermal vascular permeability. Of all the substances tested, AII, prostaglandin E1 (1 × 10−10–1 × 10−8 g), and serum triglycerides (1 × 10−6 g) produced the most marked vascular response characterized by the appearance, within 15 minutes, of a bluish wheal or papule. Injections of angiotensin I or norepinephrine at concentrations of 10–100 × 10−9 g or of Ringers solution alone did not induce skin changes. Synthetic peptides, competitive antagonists to the myotropic and vasopressor activities of AII, blocked extravasation of Evans blue dye injected simultaneously with the octapeptide, but antihistaminics did not inhibit its effects. We concluded that the multiple actions of AII in blood vessels are related not only to the control of blood pressure but also to the regulation of the permeability and the function of the vascular wall as a whole.

Arterial endothelial permeability and vascular disease the “trap door” effect

Abstract The role of sudden changes of arterial permeability to circulating macromolecules was investigated in relation to their possible role in the initiation of vascular disease. This study suggests that circulating platelets may play important roles not only in the initiation of mural thrombi, but in the maintenance of abnormal vascular permeability leading to overt vascular lesions. At the same time, it provides a working hypothesis for the study of the pathogenesis of accelerated vascular disease often found in some forms of arterial hypertension and/or intravascular thrombosis.

Production of Renin by Human Juxtaglomerular Cells in Vitro

New organ culture methods permit growth of human renal cortical cells fulfilling all known criteria of juxtaglomerular cells. Two types of granules were observed with the electron microscope. These granules showed an increase in size and number during the growth of these cultures. Their presence in cells was demonstrated by Bowies, basic fuchsin-crystal violet, and fluorochrome staining methods. Puromycin or actinomycin D caused a reduction in the number of cytoplasmic granules, while 1% oxygen in the gas phase of the culture caused an increase. Specific reaction of these granules with rabbit antihuman renin antibody was demonstrated. Other cellular structures did not react with this antibody. Similar granules were observed in the media of hyperplastic, interlobular arterioles but not in normal arterioles or arterioles of other vascular beds. Bundles of myofilaments could be observed between the cytoplasmic granules in cultured cells. Bioassays of renin activity of the supernatant culture medium showed that it contained renin if granulated cells were present in the culture. All juxtaglomerular cells in culture produced granules, but only those cells which grew from kidneys with pathological changes released renin, suggesting that the stimulus for renin release existed in the intact kidney. This stimulus for renin release seemed to be rapidly lost during culture growth.

Renin Production by Organ Cultures of Renal Cortex

Diploid cells of the human and canine renal cortex can be isolated by newly developed techniques for organ culture. Some of these cells have abundant Bowies positive granules. Bioassays for renin activity have shown that these granular cells can synthesize considerable amounts of renin in vitro. These investigations provide a model for studying the production of renin at cellular level.

The Physician's Incompleat Guide to Atherosclerosis

Excerpt It has only been some 30 years that interest in the mechanisms of atheropoiesis, or atherogenesis, has been sufficient to create almost utter confusion! Conflicting evidence and opinions ar...

Hepatic lipids of dogs fed an arteriosclerosis-inducing diet

Abstract Lipid composition of liver in dogs was investigated after feeding them either an arteriosclerosis-inducing diet which contained 16% hydrogenated coconut oil and 5% cholesterol, the same diet but without cholesterol supplement, or meat-chow. Animals fed the last diet did not develop vascular lesions and were regarded as controls. The composition and concentration of free fatty acid and phospholipid fractions of hepatic lipids from dogs fed either experimental diet for 4 months were similar but differed from controls. However, cholesteryl oleate, total cholesteryl ester and triglyceride concentrations were significantly higher in liver of the group with cholesterol supplement than in the group without cholesterol added to their diet. In addition, the cholesterol supplemented diet fed for 12–16 months caused greater hepatic lipid changes than those induced by the same diet in 4 months. Unlike adipose tissue, kidney, or myocardial and skeletal muscle, hepatic cholesterol esters showed a profound difference between the four month feedings of cholesterol supplemented and cholesterol free diets. These findings suggest that the liver may play a predominant regulatory role in the onset of diet-induced hyperlipemia and that exogenous cholesterol enhances the effects seen by feeding saturated medium chain fatty acids without cholesterol. Lipid changes observed in mitochondrial and microsomal fractions generally were similar, and also like those observed in lipid extracts of whole liver.