Grace M. Fischer

Collagen and Elastin Content in Canine Arteries Selected from Functionally Different Vascular Beds

The amount of collagen and elastin in normal canine arteries was determined biochemically in nine different sites. The total collagen and elastin ranges from 58 to 75% of the weight of the dry defatted artery. Reasons are adduced to propose that the expression of results as the ratio of collagen to elastin (C/E) is a useful index of the relative distensibility for the maintenance tension of arterial wall. Two arteries, carotid and renal, which are pathways to blood pressure sensors, have a statistically significantly higher C/E than the femoral and mesenteric arteries, which are pathways to regulated beds. The highest C/E was found in the coronary artery. Results are interpreted in relation to the function of the vascular beds to which the representative arterial specimens belong.

A possible mechanism in arterial wall for mediation of sex difference in atherosclerosis

Female rabbits on an atherogenic diet were treated with cottonseed oil (control), tamoxifen, testosterone, or progesterone. After 10 weeks the rabbits were killed, the aortas quickly removed, graded for atherosclerosis, and incubated with [14C]proline to determine collagen and elastin synthesis. Rabbits treated with testosterone and progesterone had the greatest degree of atherosclerosis, the highest DPM in hydroxyproline of collagen and elastin, and the greatest accumulation of collagen and elastin in the aorta. Tamoxifen-treated rabbits had less incorporation of radioactivity. In separate experiments aortas of similarly treated rabbits were analyzed for estradiol and progesterone receptor density. These receptors were found to be present, and progesterone and testosterone administration caused a translocation of progesterone receptors from cytosol to nucleus. Results are consistent with the hypothesis that sex hormones can affect the development of atherosclerosis through a direct effect of the hormones on arterial wall to alter collagen and elastin synthesis, the effect being mediated through hormone receptors in the wall.

Influence of contraceptive and other sex steroids on aortic collagen and elastin

Abstract The effects of estradiol, progesterone, the contraceptive steroid combination mestranol-norethynodrel (M-N), and testosterone on aortic connective tissue were studied in ovariectomized and intact female rats. Estradiol and M-N administration to ovariectomized rats resulted in decreased accumulation of aortic collagen and elastin and, after injection of rats with [14C]proline, a lower specific activity of hydroxyproline in aortic collagen and elastin. The ratio of collagen to elastin ( C E ), which is an index of passive stiffness, was relatively low in aortas of all rats receiving female hormones and high in ovariectomized oil-treated and in testosterone-treated rats. Estradiol and M-N reduced C E mainly by decreasing the percentage collagen, but progesterone reduced it by increasing the percentage elastin. It is concluded that sex hormones differentially alter aortic collagen and elastin synthesis and degradation and in so doing alter the accumulation and proportions of the two fibers in the vessel wall.

Effects of spontaneous hypertension and age on arterial connective tissue in the rat.

Abstract Weights of aorta and heart and accumulation of collagen and elastin in aorta were determined in spontaneously hypertensive and control Wistar rats of 14 weeks, six months, one year and 18 months of age. It was found that in control rats weights of aorta and heart increased as a function of age but when expressed as percent of body weight there was no change with age. However, changes in SHRs were more marked, with the aortic and heart weights increasing progressively with age to a much greater extent than in control rats. Expressed as percent body weight, aortic weight increased progressively in SHR and heart weight increased by 18 months indicating hypertrophy of the cardiovascular system in the SHR with age. Absolute quantities of connective tissues increased in aorta in both control and hypertensive rats with age. However, the accumulation was more marked in hypertensive. If connective tissue is expressed as percent of aortic weight, collagen plus elastin actually decreased as a function of age in control and to a much greater extent in SHR. The results indicate (1) increased accumulation of connective tissue in aortae of rats with age and even greater increase in aortae of hypertensive rats with age. (2) Increase in aortic smooth muscle mass with age in control and even greater increase in hypertensive aortae. It is concluded that long term spontaneous hypertension in the rat results in an increase over control rats in the major aortic wall components with smooth muscle increase greater than connective tissue increase. These changes occur in late stages of hypertension as well as early stages.

Cadmium and Zinc distribution in cardiovascular and other tissues of normal and cadmium-treated dogs.

Abstract Cadmium, zinc and water concentrations in arterial segments from 11 different sites—heart, kidney cortex and medulla, liver, spleen, diaphragm, rib and sternum—of eight normal control and eight cadmium-treated dogs were compared. Cadmium treatment resulted in significant cadmium deposition in all of the tissues analyzed. Cardiovascular cadmium distribution in normal and treated dogs revealed higher cadmium levels in more peripheral and smaller arteries in comparison with the more central arteries and the myocardium. The distal mesenteric artery, mesenteric artery branches, main renal artery and coronary arteries tended to accumulate more cadmium in normal or cadmium-treated dogs or both. Zinc distribution in cardiovascular tissues revealed the highest zinc concentration in the mesenteric artery branches of normal dogs. Cadmium was, however, preferentially retained by the normal kidney and by the kidney and liver of cadmium-treated dogs. There were significant increases in zinc concentration of the kidney, liver and sternum in response to cadmium administration. Tissue cadmium/zinc ratio increased by a factor of 7.0–282.6 after cadmium administration. There were no significant alterations in the water content of the cadmium-treated tissues. The pathophysiological implications of these data in cadmium-induced hypertension are discussed.

Tissue Cadmium and Water Content of Normal and Cadmium Hypertensive Rabbits

Cadmium concentrations in different-sized blood vessels, kidney, liver, and heart of cadmium hypertensive and control normotensive rabbits were determined by atomic absorption spectrophotometry. Normotensive kidney had a significantly higher cadmium level than that of any other normal tissue, while heart had the lowest concentration. All hypertensive tissues had significantly higher cadmium levels than the corresponding control tissues. Within the hypertensive group kidney and liver had the greatest cadmium deposition, mesenteric artery had significantly higher cadmium concentration than the aorta and heart had the lowest. There was no significant difference in the water content of normotensive and hypertensive tissues. It is suggested that the presence of cadmium ion in the blood vessels at concentration of about 1.0μg/gm wet tissue and in the kidney at a much higher concentration may have a role in the pathophysiology of cadmium hypertension.

Regional differences in magnesium, calcium, and zinc composition of arterial wall in normal and hypertensive dogs☆

Abstract Mg, Ca, and Zn content were determined in arteries from 12 different sites in the arterial tree of normal and hypertensive dogs. Regional variation of Mg tended to parallel estimated content of smooth muscle, being highest in the pulmonary and mesenteric vessels and lowest in the femoral. Ca content, on the other hand, more closely paralleled size of vessel, being highest in the great vessels. Zn content was high in the mesenteric and low in the femoral vessels. The differences between normal and hypertensive vessels were not very marked. In no site was the Mg content significantly different between normal and hypertensive vessels. In three sites, renal, thoracic aorta, and pulmonary, Ca content was significantly lower in hypertensive vessels. In one site, proximal mesenteric, Zn content was significantly lower in hypertensive vessels. It thus appears that the state of renal hypertension is not associated with a general increase in Mg, Ca, or Zn in the walls of the arterial tree.