Female Rat Aorta Research Articles

Effects of 17ß-estradiol on endothelium-dependent relaxation induced by acetylcholine in female rat aorta

Estrogens have been postulated to play an important role in modulation of vascular responses to endogenous reactive substances. The effects of chronic in vivo treatment with 17ß-estradiol on relaxant responses to acetylcholine were investigated in the rat aorta isolated from prepubertal female rats. The selectivity of effects of 17ß-estradiol on acetylcholine-induced relaxation was evaluated using histamine, another endothelium-dependent relaxant in the rat aorta. 17ß-Estradiol significantly enhanced endothelium-dependent relaxation induced by acetylcholine, but did not alter the vascular responses to acetylcholine in endothelium-denuded aortic rings isolated from prepubertal female rats. In contrast, 17ß-estradiol did not change endothelium-dependent relaxation induced by histamine in endothelium-intact aortic rings. The results of the present study demostrate that 17ß-estradiol selectively enhanced acetylcholine-induced endothelium-dependent relaxation in the rat aorta.

Chronic estrogen alters contractile responsiveness to angiotensin II and norepinephrine in female rat aorta

Sex hormones have been postulated to play an important role in the modulation of vascular responsiveness to endogenous vasoactive substances. This study was designed to establish the effects of chronic treatment with estrogen in vivo on subsequent contractile responsiveness of aortic rings to angiotensin II or norepinephrine in vitro. Concentration-response curves for angiotensin II were compared in aortic rings with or without endothelium isolated from ovariectomized rats (275–299 g) pretreated with 17β-estradiol (≈ 1 mg/kg per day) or placebo for 14 days and from normal prepubertal female rats (125–149 g) pretreated with 17β-estradiol (≈ 5 mg/kg per day) or placebo for 14 days. Whether or not endothelium was present, angiotensin II-induced contraction was significantly depressed in rings from 17β-estradiol-treated ovariectomized or prepubertal rats when compared to controls, and the pattern of the effects of 17β-estradiol-treatment on the concentration-response curves for angiotensin II was similar in the two models. In contrast to angiotensin II-induced contraction, norepinephrine-induced contraction was significantly enhanced in aortic rings with or without endothelium from ovariectomized rats pretreated with 17β-estradiol (≈ 1 mg/kg per day, 14 days) and from normal prepubertal female rats pretreated with 17β-estradiol (≈ 5 mg/kg per day, 14 days) when compared to controls. The results demonstrate that chronic treatment with 17β-estradiol selectively reduced and enhanced contractile responsiveness of aortic rings to angiotensin II and norepinephrine, respectively. Further, the results indicate that the normal prepubertal female rat is an efficient model to investigate modulation by estrogen of aortic responsiveness to vasoactive agents in vitro.

Effects of estrogen pretreatment of the spare α1-adrenoceptors and the slow and fast components of the contractile response of the isolated female rat aorta

1. 1. Estrogen pretreatment increases the responsiveness to noradrenaline and to clonidine in isolated rat female aortae. 2. 2. Determinations of the pK A and pA 2 of noradrenaline and prazosin, respectively suggest that the isolated female aorta possess a homogeneous α 1-adrenoceptor population. 3. 3. The fast and slow components of clonidine-induced aorta contraction were determined using nifedipine. 4. 4. Considering that after estrogen pretreatment, an increase in spare α 1-adrenoceptors probably occur and only the fast component of clonidine-induced contraction was enhanced we concluded that estrogen pretreatment increases the number of α 1-adrenoceptors and the amount of intracellular calcium available for contraction.

Sexual dimorphism in vasopressin-induced contraction of rat aorta

Previously, we reported that, in the rat, pressor responsiveness to vasopressin (VP) is higher in males than in females during most phases of the estrous cycle. To explore the role of the vasculature in this phenomenon, we examined vascular reactivity to VP in thoracic aortas of male rats and female rats during each phase of the estrous cycle. Aortic rings were prepared from age-matched male and female Sprague-Dawley rats and mounted for isometric tension recording. Maximal response of female aortas to VP (4,246 +/- 163 mg/mg ring dry wt) was more than twice (P less than 0.001) that of male aortas (1,877 +/- 215 mg/mg ring wt). Sensitivity of female aortas to VP was substantially higher (P less than 0.001) than that of male aortas (EC50: 10.9 +/- 0.7 vs. 19.0 +/- 1.6 nM, respectively). Maximal rate of tension development (dT/dtmax) during contraction with VP was nearly twofold higher (P less than 0.01) in female aortas (536 +/- 23 mg/min) than in male aortas (300 +/- 19 mg/min). Maximal response, sensitivity, and dT/dtmax of female aortas did not vary significantly during the estrous cycle. Maximal response of female aortas to phenylephrine (PE; 1,251 +/- 93 mg/mg ring wt) was half that (P less than 0.001) of male aortas (2,546 +/- 194 mg/mg ring wt); sensitivity to PE did not differ significantly (EC50: 0.33 +/- 0.02 vs. 0.38 +/- 0.06 microM, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Stimulation of vascular prostacyclin production by bradykinin

To characterize the mechanism of bradykinin stimulation of prostacyclin (PGI2) production in rat thoracic aorta, we have investigated the sex difference in response to bradykinin and the roles of Ca2+ and calmodulin. Thoracic aortae were prepared from both sexes of Wistar strein rats (8-10 weeks). PGI2 production was determined by a bioassay and radioactive pre-labeling with 3H-arachidonic acid. PGI2 was rapidly produced by rat aorta, and there was a slightly difference in that female rat aorta produced more PGI2- Addition of bradykinin stimulated PGI2 production, and the stimulated rate was more in female rat aorta. Mepacrine abolished the action of bradykinin.

Mineralized deposits in the thoracic aorta of aged rats: Ultrastructural and electron probe x-ray microanalysis study

The thoracic aorta of male and female virgin rats aged from 26–30 months was studied by electron microscopy and electron probe X-ray microanalysis. In all rats (but especially the oldest female) several types of calcified mineral deposits were identified: (a) Ovoid, membrane-bound, amorphous mineral interspersed with fine needle-like crystals; these were found in intact but degenerating arterial cells, and their size and distribution suggested that they were highly calcified mitochondria. (b) Extracellular spherular deposits located in pleomorphic necrotic debris; two distinct types; (i) amorphous or concentrically- layered spherites with characteristics electron-dense periphery, 0.25–0.8 μm diameter, Ca : P = 1.24 ± 0.02, and with significant Mg content (Ca : Mg = 16.7 ± 2.5); (ii) less regularly shaped granules composed of denser material, Ca : P more variable (1.30 ± 0.18), but not detectable Mg. (c) Spiculate crystal lumps which appeared to grow on the microvesicular component (25–100 nm) of the pleomorphic debris. No evidence was found of calcium deposition on or within elastic or collagen fibres. We concluded that age-related arterial calcification is probably initiated within the mitochondria of degenerating vascular smooth muscle cells, and possibly also in the extracellular spaces within lysed, submitochondrial particles.

Effects of estrogen treatment on the oophorectomized female rat aorta.

SummaryThe postmenopausal state appears to be associated with an increased incidence of atherosclerotic vascular disease in women. Connective tissue and cellular changes in the female rat thoracic aorta were studied in oophorectomized mature rats with and without estrogen replacement. In one study, no attempt was made to control the increased growth of the oophorectomized female. However, because of the possible contribution of different growth rates to results, in another study, weights of the treated and nontreated groups were balanced by pair-feeding. Both studies showed the same qualitative results. Total DNA contents of anatomically-defined thoracic aortic segments were not affected by oophorectomy or by estrogen replacement. Significant and similar increments in total aortic elastin and collagen were seen in untreated oophorectomized groups compared to estrogen-treated ones; a significant increase in percentage of collagen was found. Accelerated accumulation of connective tissue in the rat aortic wa...

The aortic tunica intima in young and aging rats

The tunica intima of aortas of female rats ranging in age from 0 to 36 months were examined in the electron microscope. Aortas were fixed at their physiological length, and examined in cross- and longitudinal section as well as in an “en face” orientation. The latter revealed an endothelium containing large amounts of ergastoplasm and golgi in both very young and very old rats. At all ages studied, the endothelial plasma membranes are pitted with caveolae which are seen in large numbers in the “en face” orientation. Bundles of cytoplasmic filaments are present near the abluminal surfaces of the endothelial cells and appear to have structural connections with anchoring filaments in the subendothelial space. Lipid inclusions are frequently seen in the aortic endothelium of rats from two years of age on. Lipid and granular inclusions are also seen at these ages in subendothelial intimal cells which are thought to be of two types, either blood-derived or modified medial smooth muscle. The mechanism by which medial muscle cells enter the intima is discussed in terms of either cell migration or physiological remodeling of the vessel wall. The subendothelial space in young rats is filled with a watery matrix which with age is infiltrated by cells, amorphous granulo-vesicular debris and crystalline bodies. This accumulation of material in the subendothelial space results in a diffuse intimal thickening in the absence of appreciable extracellular lipid.

Effects of hypertension and its reversal on the thoracic aorta of male and female rats. Morphological and chemical studies.

Effects of hypertension and its reversal on the wall of the thoracic aorta of male and female rats were studied. Hypertension for 10 weeks caused increased diameter, wall thickness, tangential tension, wall stress, and medial area in both sexes. In addition, absolute amounts of elastin, collagen, and noncollagenous, alkali-soluble protein were significantly increased in the walls of all hypertensive vessels. Associated with the decrease of calculated tension and wall stress to normotensive levels after reversal of hypertension, wall thickness and medial area in males remained significantly greater than in controls and similar to the values found in hypertensive vessels, whereas in females these parameters returned fully to control levels. Absolute amounts of noncollagenous, alkali-soluble proteins did return to control levels after hypertension reversal, but elastin and collagen remained elevated in amounts similar to those in vessels with sustained hypertension; in females, this resulted in an above-normal concentration of these fibrous elements in the vessel wall. Compositional changes of the female vessel wall after reversal of hypertension were thus similar to but more clearcut and complete than those found in the male aorta. Recognition of irreversible changes in vessels subjected to hypertension may have implications for the benefits to be gained from blood pressure reduction on the progression of cardiovascular disease.

The aortic tunica media in aging rats

The tunica media of aortas of female breeder rats ranging in age from 5–36 months were examined by light and electron microscopy. Similar material previously obtained from newborn to 3-month-old female rats was used for light microscopy. Aortas were fixed at their physiological lengths. With age the tunica media in section doubled in thickness while its cellularity was halved. The media showed increasing randomization with age with collagen fibrils becoming distributed very diffusely and elastica in the laminae being redistributed in a network in which laminae and interlaminar elastic tracts were of similar sizes. The cells increased progressively in size and (most particularly at 24 months of age) came to contain large quantities of organelles characteristic of synthesizing and secreting cells and corresponded in appearance to “myo-intimal” cells and other forms of reactive smooth-muscle cells. The increase in wall thickness and presence of these organelles suggest continuing fibrilogenesis in the aging media. The hypertrophied cells developed irregular surfaces that formed lacework margins, presumably helping to maintain satisfactory surface-to-volume ratios. The decreasing cellularity of the media also could be attributed in part to the increasing cell degeneration and necrosis identified with age. Degenerative changes involving both nucleus and cytoplasm of the cells were identified. The cytoplasmic changes involved accumulation of lipids with foam-cell appearances developing at times. In addition, various granular and vesicular forms of cytoplasmic degeneration occurred and resulted in similar debris being liberated into the extracellular space where it remained without producing any detectable reaction.

5-nucleotidase activity in aortas of arteriosclerotic breeder rats

The activity of the enzyme, 5-nucleotidase was measured, chemically and histochemically, in the aortas of male and female control rats, free of arterial disease, as well as male and female breeder rats which develop microscopic and grossly-visible arteriosclerosis of the aorta, respectively. Female rats manifested much greater aortic 5-nucleotidase activity than male rats. Very little difference could be detected between the aortic enzyme activity of male control rats and male breeder rats which had aortic microscopic lesions only. However, there was a significant and progressive increase in aortic 5-nucleotidase activity commensurate with and paralleling the progression of the severity of arteriosclerosis as well as its anatomical spread from the abdominal aortic segment to the arch and lastly, the thoracic aortic segment. The histochemical tests demonstrated that 5-nucleotidase activity first appears in the tunica intima coincidental with the appearance and accumulation of mucopolysaccharide. As the intimal mucopolysaccharide is converted into collagen the 5-nucleotidase activity disappears. In the media, 5-nucleotidase activity becomes diffusely and strongly positive in close proximity to the internal elastic membrane. As the medial degenerative changes become more exacerbated and calcific changes appear the 5-nucleotidase reaction becomes most intense. These chemical and histochemical observations are construed to be an indication of the hormonal effects of repeated breeding inducing medial smooth muscle cell changes in association with 5-nucleotidase activity to affect ground substance and connective tissue changes which favor sclerosis and calcification of the aortic wall of breeder rats.

Atheromatous plaques in aortas of essential fatty acid deficient rats.

SummaryGross atherosclerotic plaques were produced in the abdominal aortas of female rats maintained for one year on a diet deficient in essential fatty acids but with an elevated content of cholesterol and saturated fat. Male rates were not similarly affected.

AORTIC LIPOPROTEIN LIPASE ACTIVITY IN RELATION TO SPECIES, AGE, SEX, AND BLOOD PRESSURE.

It has been suggested that lipoprotein lipase (LPL) activity may play a role in the etiology of atherosclerosis. To determine whether there is an inverse relationship between arterial LPL activity and the tendency for arteries to become atherosclerotic, determinations were made of the activities of the enzyme in homogenates of the aortas of animals under conditions associated with a greater or lesser tendency for atherosclerosis to develop. It was found that the LPL activities of the aortas of old rats and rabbits were significantly lower than those of young animals of the same species, respectively. Rats, which are resistant to the development of atherosclerosis, manifested about twice the aortic LPL activities that rabbits did, the latter animals being notorious for the ease with which they develop the disease. This was true regardless of the age and sex of the animals compared. These results support the hypothesis that low arterial LPL activity may be associated with increased atherogenesis. Aortas of female rats or rabbits, however, showed no greater LPL activities than did aortas of males of the same species. Renal and desoxycorticosterone-salt hypertensions were accompanied by significant increases rather than decreases in aortic LPL activity. The latter results are not consonant with the aforementioned hypothesis.

CYCLIC CHANGES IN THE OXYGEN CONSUMPTION OF THE AORTA IN FEMALE RATS.

The endogenous oxygen consumption of aorta and of diaphragmatic muscle have been studied in female rats and correlated with different phases of estrus. Cyclic changes of oxygen consumption were demonstrated in the aorta but not in the diaphragm. Estradiol in vitro depressed the endogenous Qo 2 of the aorta from diestrous animals. Possible implications of this work are discussed.

Influence of the gonads on aortic oxygen uptake in rats

Summary The endogenous oxygen uptake has been determined in the aorta of male and female rats. Intact, gonadectomized and gonadectomized hormone-injected animals were studied. No differences were found between male and female rats. Orchiectomy and oophorectomy increased the oxygen uptake, which was reduced to normal values by the injection of estradiol or testosterone into gonadectomized animals. When estradiol or testosterone was added to the aorta in vitro , no changes were induced in the aortic Q O2 of normal animals, but when either hormone was added to aortas from gonadectomized rats the Q O2 value was reduced. The possible connection of the gonadal control of aortic metabolism with the development of atherosclerosis is discussed.

Arteriosclerosis in the rat: aortic enzyme changes accompanying arterial pathology.

Summary(1) Extracts of arteriosclerotic aortas of female Sprague-Dawley breeder rats were assayed for lactic dehydrogenase, glucoses-phosphate dehydrogenase, and 6-phos-phogluconic dehydrogenase. (2) Extracts obtained from moderately and severely arteriosclerotic aortas contained significantly less lactic dehydrogenase than extracts of aortas grossly normal or only slightly affected. TPNH production by combined action of glucose-6-phosphate dehydrogenase and 6-phosphogluconic dehydrogenase was significantly depressed in extracts from moderately and severely arteriosclerotic aortas. No significant differences were observed in levels of 6-phos-phogluconic dehydrogenase.

Connective tissue. I. Age and sex influence on protein composition of rat tissues.

SummaryTissues from tail tendon, aorta, skin, uterus, lung, muscle, heart, liver, kidney and spleen of male and female rats at 3–5 wk, 8 mo and 2 yr of age were fractionated into soluble protein, insoluble collagen and elastin. Amount of soluble collagen in the soluble protein fraction was calculated according to amount of hydroxyproline. Significant changes in these fractions with age occurred only in skin, tendon, uterus and aorta, with scleroprotein increased and non-scleroprotein decreased.