[Influence of psychiatric diseases and psychiatric medication to the severity of clinical outcome of COVID-19].

Initially, it had been assumed that in cases of SARS-CoV-2 infection comorbidity with psychiatric disorders worsens clinical outcomes. This was attributed to patients' poor overall health conditions, concomitant illnesses and unhealthy lifestyles. However, only schizophrenia is in a statistically significant correlation with very serious conditions leading to death, possibly as a result of underlying immune dysfunctions. Clozapine (an antipsychotic used in therapy of treatment resistant schizophrenia) seems to decrease the likelihood of recovery in COVID-19 patients, however admi nistration of antidepressant medications appears to increase it. It has also been justified that among these antidepressant drugs, fluvoxamin shows to have an effect in inhibiting cytokine storms and reducing the severity of the COVID-19 infection. Most recent data suggest that the well-known antiviral effect of lithium is also present in patients with COVID-19 infection.

Effects of Testosterone Deficiency and Angiotensin II-Induced Hypertension on the Biomechanics of Intramural Coronary Arteries.

BACKGROUND: Andropause and hypertension also increase the risk of coronary artery damage. AIM: To investigate the effect of testosterone deficiency and hypertension on intramural coronary vessels. METHODS: 4 groups of 8-week-old Sprague-Dawley rats were studied: control male (Co, n=10), orchidectomized male (OCT, n=13), angiotensin (AII) hypertensive male (AII, n=10), and AII hypertensive and OCT (AII + OCT, n=8). Surgical orchidectomy was performed, and an osmotic minipump was inserted for chronic angiotensin II infusion (100 ng/min/kg). After 4 weeks, spontaneous tone and biomechanical properties of the intramural coronary resistance artery were investigated in vitro, by pressure microarteriography. OUTCOMES: Morphology and biomechanics of the intramural coronaries were evaluated: the outer diameter, wall thickness-to-lumen diameter ratio, and tangential wall stress in the contracted and relaxed states. RESULTS: The outer diameter was reduced in OCT and AII + OCT groups (on 50 mmHg 315 ± 20 Co; 237 ± 21 OCT; 291 ± 16 AII, and 166 ± 12 µm AII + OCT). The increased wall thickness-to-lumen diameter ratio resulted in lower tangential wall stress in AII + OCT rats (on 50 mmHg 19 ± 2 Co; 24 ± OCT; 26 ± 5 AII, and 9 ± 1 kPa AII + OCT). Spontaneous tone was increased in the hypertensive rats (AII and AII + OCT groups) (on 50 mmHg 7.7 ± 1.8 Co; 6.1 ± 1.4 OCT; 14.5 ± 3.0 AII, and 17.4 ± 4.1 % AII + OCT). CLINICAL IMPLICATIONS: Andropause alone can be considered as a cardiovascular risk factor that will further exacerbate vascular damage in hypertension. STRENGTHS & LIMITATIONS: A limitation of our study is that it was performed on relatively young rats, and the conclusions might not apply to coronary remodelling in older animals with slower adaptation processes. CONCLUSIONS: Testosterone deficiency and hypertension damage the mechanical adaptation of the vessel wall additively: double noxa caused inward eutrophic remodeling and increased tone. Jósvai A, Török M, Mátrai M, et al. Effects of Testosterone Deficiency and Angiotensin II-Induced Hypertension on the Biomechanics of Intramural Coronary Arteries. J Sex Med 2020;17:2322-2330.

European postgraduate curriculum in geriatric medicine developed using an international modified Delphi technique.

BACKGROUND: the European Union of Medical Specialists (UEMS-GMS) recommendations for training in Geriatric Medicine were published in 1993. The practice of Geriatric Medicine has developed considerably since then and it has therefore become necessary to update these recommendations. METHODS: under the auspices of the UEMS-GMS, the European Geriatric Medicine Society (EuGMS) and the European Academy of Medicine of Ageing (EAMA), a group of experts, representing all member states of the respective bodies developed a new framework for education and training of specialists in Geriatric Medicine using a modified Delphi technique. Thirty-two expert panel members from 30 different countries participated in the process comprising three Delphi rounds for consensus. The process was led by five facilitators. RESULTS: the final recommendations include four different domains: 'General Considerations' on the structure and aim of the syllabus as well as quality indicators for training (6 sub-items), 'Knowledge in patient care' (36 sub-items), 'Additional Skills and Attitude required for a Geriatrician' (9 sub-items) and a domain on 'Assessment of postgraduate education: which items are important for the transnational comparison process' (1 item). CONCLUSION: the current publication describes the development of the new recommendations endorsed by UEMS-GMS, EuGMS and EAMA as minimum training requirements to become a geriatrician at specialist level in EU member states.

Antioxidant effect of the active metabolites of tibolone.

Certain steroidal compounds have an antioxidant effect in humans. Our aim was to test whether the synthetic steroid tibolone and its metabolites are also able to display such a property. For this, granulocytes from healthy men and women were incubated for two hours with different concentrations (10(-7), 10(-8), 10(-9 )M) of either estradiol, tibolone, 3α-hydroxytibolone, 3ß-hydroxytibolone, Δ(4)-tibolone, 3α-sulfated-tibolone, 3α-17ß-disulfated-tibolone, 3ß-sulfated-tibolone or 3ß-17ß-disulfated-tibolone. Superoxide anion generation of neutrophils was measured by photometry. Results of different steroids were given as percentages of their controls. A more simple superoxide generating system, the xanthine-xanthine oxidase reaction was also tested. We found that granulocyte superoxide production did not differ from the control using 10(-9 )M of steroids. Using 10(-8 )M concentration: estradiol (80.9 ± 2.5%); 3ß-sulfated-tibolone (83.3 ± 4.7%); 3ß-17ß-disulfated-tibolone (81.0 ± 4.2%) caused a significant decrease in superoxide production, compared to the control. In addition at 10(-7 )M, 3ß-hydroxytibolone and 3α-sulfated-tibolone also showed antioxidant effects. In the xanthine-xanthine oxidase system estradiol (67.4 ± 1.0%), 3α-sulfated-tibolone (85.8 ± 5.3%), 3α-17ß-disulfated-tibolone (71.9 ± 2.5%), 3ß-sulfated-tibolone (73.9 ± 5.0%), and 3ß-17ß-disulfated-tibolone (65.8 ± 3.4%) caused a significant decrease in superoxide production. Conclusively, although tibolone itself did not show significant antioxidant capacity, most of its active metabolites have antioxidant effects.

The effect of indomethacin, myeloperoxidase, and certain steroid hormones on bactericidal activity: an ex vivo and in vivo experimental study.

BACKGROUND: The role of myeloperoxidase (MPO) is essential in the killing of phagocytosed bacteria. Certain steroid hormones increase MPO plasma concentration. Our aim was to test the effect of MPO, its inhibitor indomethacin, and certain steroid hormones on bactericidal activity. METHODS: Human polymorphonuclear leukocytes (PMN) were incubated with opsonised Escherichia coli and either MPO, indomethacin, estradiol, or hydrocortisone. Intracellular killing capacity was evaluated with UV microscopy after treatment with fluorescent dye. Next, an in vivo experiment was performed with nine groups of rats: in the first phase of the study indomethacin treatment and Pasteurella multocida infection (Ii), indomethacin treatment without infection (I0), untreated control with infection (Mi) and untreated control without infection (M0); in the second phase of the study rats with infection and testosterone treatment (NT), castration, infection and testosterone treatment (CT), castration, infection and estradiol treatment (CE), non-castrated infected control (N0), and castrated infected control (C0). After treatment bacteria were reisolated from the liver and heart blood on agar plates, and laboratory parameters were analyzed. For the comparison of laboratory results ANOVA or Kruskal-Wallis test and LSD post hoc test was used. RESULTS: Indomethacin did not have a remarkable effect on the bacterial killing of PMNs, while the other compounds increased bacterial killing to various degrees. In the animal model indomethacin and infection caused a poor clinical state, a great number of reisolated bacteria, elevated white blood cell (WBC) count, decreased C-reactive protein (CRP) and serum albumin levels. Testosterone treatment resulted in less bacterial colony numbers in group NT, but not in group CT compared to respective controls (N0, C0). Estradiol treatment (CE) decreased colony numbers compared to control (C0). Hormone administration resulted in lower WBC counts, and in group CE, a decreased CRP. CONCLUSIONS: MPO, estradiol, and hydrocortisone improve bacterial killing activity of PMNs. Indomethacin treatment and castration weaken immune responses and clinical state of infected rats, while testosterone and estradiol have a beneficial effect.

The effect of certain steroid hormones on the expression of genes involved in the metabolism of free radicals.

Steroid hormones influence the antioxidant processes of cells. However, the molecular mechanism of this effect is not fully clear. Our aim was to examine how steroid hormones affect the expression of certain genes that play a role in antioxidant processes. Blood was taken from ten healthy volunteers. Neutrophil granulocytes were separated and treated either with 17-ß-estradiol, progesterone, testosterone, or cortisol. Whole RNA was isolated and reverse transcription was carried out in treated and control groups. Relative quantification was performed with SYBR Green assay and gene-specific oligonucleotides. We found that the expression of Mn-superoxide dismutase was significantly increased by 17-ß-estradiol and testosterone, myeloperoxidase expression was significantly elevated by cortisol and progesterone, and the expression of NADPH oxidase was significantly decreased by progesterone. We conclude that the antioxidant effect of steroid hormones is in part carried out through transcriptional regulation of certain enzymes. Subsequent studies are required in order to examine the non-genomic, membrane receptor mediated effect of steroids on antioxidant processes.

Additive damage in the thromboxane related vasoconstriction and bradykinin relaxation of intramural coronary resistance arterioles in a rodent model of andropausal hypertension.

Hypertension and andropause both accelerate age-related vascular deterioration. We aimed to evaluate the effects of angiotensin-II induced hypertension and deficiency of testosterone combined regarding the resistance coronaries found intramurally. Four male groups were formed from the animals: control group (Co, n = 10); the group that underwenr orchidectomy (ORC, n = 13), those that received an infusion of angiotensin-II (AII, n = 10) and a grous that received AII infusion and were also surgically orchidectomized (AII + ORC, n = 8). AII and AII + ORC animals were infused with infusing angiotensin-II (100 ng/min/kg) using osmotic minipumps. Orchidectomy was perfomed in the ORC and the AII + ORC groupsto establish deficiency regarding testosterone. Following four weeks of treatment, pressure-arteriography was performed in vitro, and the tone induced by administration of thromboxane-agonist (U46619) and bradykinin during analysis of the intramural coronaries (well-known to be resistance arterioles) was studied. U46619-induced vasoconstriction poved to be significantly decreased in the ORC and AII + ORC groups when compared with Co and AII animals. In ORC and AII + ORC groups, the bradykinin-induced relaxation was also significantly reduced to a greater extent compared to Co and AII rats. Following orchidectomy, the vasocontraction and vasodilatation capacity of blood vessels is reduced. The effect of testosterone deficiency on constrictor tone and relaxation remains pronounced even in AII hypertension: testosterone deficiency further narrows adaptation range in the double noxa (AII + ORC) group. Our studies suggest that vascular changes caused by high blood pressure and testosterone deficiency together may significantly increase age-related cardiovascular risk.

Increased total scavenger capacity and decreased liver fat content in rats fed dehydroepiandrosterone and its sulphate on a high-fat diet.

BACKGROUND: Weak androgens have an antioxidant effect in vitro which is represented as a beneficial change in the antioxidant status. OBJECTIVE: Our aim was to clarify whether dehydroepiandrosterone (DHEA) and dehydroepiandrosterone-sulphate (DHEAS) oral administration results in beneficial antioxidant changes in Sprague-Dawley adult male rats in vivo. METHODS: Groups of experimental animals were fed a high-fat or a normal-fat diet and treated with DHEA or DHEAS in the drinking fluid. The control group was fed a high-fat diet together with untreated drinking fluid. Total scavenger capacity (TSC) was measured before and after 4 weeks of treatment in blood samples using a chemiluminometric assay. Fat content, superoxide dismutase (SOD), catalase and glutathione S-transferase (GST) activity in the liver were determined by Sudan staining and spectrophotometric assessments, respectively, from the fresh frozen tissue. RESULTS: DHEA and the DHEAS treatment showed significantly increased TSC in the groups fed a high-fat diet. The control group and the DHEA- or DHEAS-treated groups on normal diets showed no significant changes in TSC. The total score of liver fat content in the high-fat diet groups showed a marked positivity with Sudan staining, and the groups treated with DHEA or DHEAS had a markedly decreased amount of fat in the liver slides compared to the untreated group on the high-fat diet. Liver SOD activity was decreased in all high-fat diet groups and elevated only in the groups on a normal diet with DHEA or DHEAS treatment. Liver catalase and GST activities were decreased in the groups where TSC was significantly increased. CONCLUSION: Our results support the hypothesis that DHEA and DHEAS supplementation can improve the antioxidant status in lipid-rich dietary habits.

Athletic fitness development with electronic monitoring in older adult / Sportolás elektronikus monitorozással idoskorban.

Összefoglaló. Idosebb korban a testgyakorlás különösen fontos az izmok sorvadásának megelozése, valamint a vérnyomás és a testsúly kontrollja céljából. Ma már egyre gyakoribb az idoskorúak részvétele sportversenyeken is. Esettanulmányunk célja a késo felnottkori, illetve idoskori versenyszeru sportolás egészségi alkalmassági feltételeinek, kockázatainak és a teljesítoképesség változásainak bemutatása az elektronikus monitorozás és virtuális versenyzés korában. Esetünkben ez egy idoskorú személy 16 év során (54-70 éves kor) teljesített maratoni futóversenyeinek, valamint virtuális evezoversenyek részvételi és felkészülési adatainak elemzésével valósul meg. Esetünk illusztrálja, hogy az észszeru túlterhelés elve alapján az izmok adaptációja akkor következik be, amikor az edzés terhelése meghaladja az addig már elért terhelési szintet. A sportóra használata az elektronikus pulzusszám és a teljesítmény monitorozásával nemcsak a versenyek és edzések alatt a pulzusszám céltartományban tartására, de hosszabb távú tendenciák felismerésére is hasznosnak bizonyult. Az egészségi állapotnak megfelelo (sportág és intenzitás) idoskori testgyakorlás és sportversenyen való részvétel nemcsak az eronlét megtartását tuzheti ki célul, hanem értékes eronlétfejlesztést is. Orv Hetil. 2021; 162(51): 2061-2066. Summary. With advancing age, exercise becomes particularly important to prevent muscle atrophy and to control blood pressure and weight. Today, participation of aging people in athletic competitions is increasingly common. The aim of our case study is to explore and illustrate the health conditions, development and risk factors of competitive sporting activities of late adult and elderly athletes in the age of electronic monitoring and virtual racing. We processed the preparation and participation data of a total of 16 years of marathon races as well as rowing machine races of an elderly male person (age 54-70). Using a sports watch with electronic heart rate and performance monitoring has proved useful not only for keeping the heart rate in target range, but also for assessing trends in the long run. Our case underscores the value of reasonable overload with advancing age; beneficial muscle adaptation occurs when the workload of an exercise exceeds the previously reached level. Gradual exercise of older adults and participation in athletic competitions can not only maintain fitness but also develop valuable additional strength. Orv Hetil. 2021; 162(51): 2061-2066.

Biomechanics of resistance artery wall remodeling in angiotensin-II hypertension and subsequent recovery.

BACKGROUND/AIMS: To identify the relationship between systemic and local hemodynamics, as well as segmental biomechanical properties in a musculocutaneous resistance artery during angiotensin-II hypertension and its recovery. METHODS: Rats were infused with angiotensin-II using implanted osmotic minipumps (ALZET 2ML4, 150 ng/kg/min) for 4 weeks. Measurements were made either immediately following infusion or after an additional 4-week recovery period. Parallel controls were created. Segmental geometry and blood flow were determined in vivo on microsurgically exposed segments of the saphenous arterial branch (350 mum). Pressure-radius plots of excised cylindrical segments were recorded by pressure arteriography. RESULTS: Eutrophic hypertensive wall remodeling developed, with reduced passive radius, increased wall thickness, elevated low-stress elastic modulus, reduced norepinephrine contraction, and reduced endothelium-mediated dilation. Relaxed wall geometry fully healed in 4 weeks of recovery, but an increased contractility and a reduced in vivo lumen persisted. Regional hemodynamic resistance correlated positively with systemic arterial pressure and wall thickness in vivo, and negatively with in vivo lumen size throughout these studies. CONCLUSION: A partial recovery of the biomechanical parameters was found. Healing of eutrophic hypertensive remodeling of the resistance artery wall is a complex biomechanical process, not a simple reversal of the original pathological sequel.

Morphological remodeling of the intramural coronary resistance artery network geometry in chronically Angiotensin II infused hypertensive female rats.

Segmental remodeling of resistance arteries, inhibition of angiogenetic processes, their rarefaction by AngiotensinII and hypertension are accepted facts. Less is known about alterations in resistance artery network geometry potentially induced by them. Female rats were infused with 100 ng/kg/min AngiotensinII with osmotic minipumps for four weeks that raised mean arterial blood pressure from 98 ± 3 to 125 ± 7 mmHg. Geometry of the left coronary artery system was studied on plastic casts and on in situ microsurgically prepared, saline infused video-microscoped networks (n = 13 and 11 controls and hypertensives, respectively). Parallel running branches, broken course of larger branches, multiple branchings and branch crossings have been identified (13 and 74 such deformities, in control and hypertensive networks, respectively, p < 0.01). Bifurcation angles increased with increasing asymmetry of daughter branches but not in hypertensives. Dividing the whole network (theoretically) into several hundreds of 50µm long ring units, ring frequency peaked at 200µm diameter in normal networks. This peak diminished and was replaced by a peak at 300µm in hypertensives (p < 0.01). In controls, diameter of vascular units decreased at a fairly even rate with flow distance from the orifice. The 350, 200, 150µm diameter units were found with highest frequencies at flow distances around 2.5, 5.5 and 7.5mm, respectively. This regular pattern disintegrated in hypertensives. Higher blood flow routes were needed to cover the same distance from the orifice (p < 0.01). Shrinkage and diminishment of many parallel connected 200µm segments, concomitant enlargement of many larger segments accompanied with morphological deformities can be expected to contribute to elevated vascular resistance.

Effects of estrogen and progestin on the CO2 sensitivity of hemispheric cerebral blood volume.

OBJECTIVE: High CO2 sensitivity is one of the major characteristics of the cerebrovascular bed. It has been shown to be influenced by many differrent factors (eg, sex hormones). DESIGN: The effect of ovariectomy and subsequent female sexual hormone treatment on the steady-state hemispheric cerebral blood volume and CO2 responsiveness of the hemispheric blood vessels was studied on anesthetized, ventilated, normotensive, normoxic rats. Cerebral blood volume was measured with Tomita's photoelectric method with Sandor's modification. RESULTS: Steady-state cerebral blood volume values in ovariectomized rats did not differ from those found in control animals. The CO2 responsiveness of hemispheric blood vessels was higher in ovariectomized and progestin-treated, but not estrogen-treated, animals compared with controls. CONCLUSIONS: Our results demonstrate that the CO2 sensitivity of the hemispheric vessels is sex hormone dependent. Estrogen and progestin treatment have opposite effects on this cerebral circulatory parameter.

Gender differences in biomechanical properties of intramural coronary resistance arteries of rats, an in vitro microarteriographic study.

The prevalence of ischemic heart disease is lower in premenopausal females than in males of corresponding age. This should be related to gender differences in coronary functions. We tested whether biomechanical differences exist between intramural coronary resistance arteries of male and female rats. Intramural branches of the left anterior descending coronary artery (uniformly approximately 200microm in diameter) were isolated, cannulated and studied by microarteriography. Intraluminal pressure was increased from 2 to 90mmHg in steps and steady-state diameters were measured. Measurements were repeated in the presence of vasoconstrictor U46619 (10(-6)M) and the endothelial coronary vasodilator bradykinin (BK) (10(-6)M). Finally, passive diameters were recorded in calcium-free saline. A similar inner radius and a higher wall thickness (41.5+/-2.9microm vs. 31.4+/-2.7microm at 50mmHg in the passive condition, p<0.05) resulted in lower tangential wall stresses in male rats (18.9+/-1.9kPa vs. 24.9+/-2.5kPa at 50mmHg, p<0.05). Isobaric elastic modulus of vessels from male animals was significantly smaller at higher pressures. Vasoconstrictor response was significantly stronger in male than in female animals. Endothelial relaxations induced by BK were not different. This is the first demonstration that biomechanical characteristics of intramural coronary resistance arteries of a mammalian species are different in the male and female sexes. Higher wall thickness and higher vascular contractility in males are associated with similar endothelial function and larger high-pressure elasticity compared to females. These gender differences in biomechanics of coronary resistance arteries of rats may contribute to our better understanding the characteristic physiological and pathological differences in humans.

The effect of estrogens on superoxide anion generation by human neutrophil granulocytes: possible consequences of the antioxidant defense.

The present study aimed to test whether, beyond the known antioxidant effect of estradiol, such a property is also possessed by estrone and estriol. For this purpose, an in vitro investigation of the effect of estrone and estriol on superoxide anion production by human neutrophil granulocytes was carried out. Blood samples were obtained from healthy volunteers and neutrophil granulocytes were separated for measurement of superoxide anion generation after incubation with estrone, estriol (10(-7), 10(-6) and 10(-5) M) and 17beta-estradiol (10(-7) M). Superoxide anion production of isolated neutrophil granulocytes was quantified by photometry and using the reduction of ferricytochrome-C. When adding estrone and estriol to neutrophil granulocyte suspensions, the production of superoxide anion fell (10(-5) M: 84.17 +/- 3.14% and 88.77 +/- 1.98% of control production, p < 0.01 and p < 0.05, respectively). Estradiol produced an antioxidant effect at lower concentration (10(-7) M: 72.91 +/- 7.94% of control production, p < 0.001). The weak estrogens estrone and estriol, similarly to estradiol, are also able to reduce the superoxide anion release in our experimental model. This may have importance in the antioxidant defense of biological systems.

[The molecular biology of aging--therapeutic interventions?]. / Az öregedés molekulárbiológiai meghatározói-- terápiás lehetoségek?

Aging is a complex mechanism of progressive and irreversible processes occurring to molecules, to cells and to the whole organism and ending with death. Genetic - so called "programmed" - factors and the combination of environmental interactions play the most important role in its development. Changes in macromolecules caused by free radicals, non-enzymatic glycosylation and apoptosis have a special role in the pathomechanism of aging. Endocrine and immune systems have also an important influence and control on the process. Those environmental effects, as for example irradiation, toxic chemicals, metal ions, free radicals play a determinant role in the development of aging. Diseases of old age should be distinguished from aging per se, although changes in old age increase the frequency of diseases. Those aging changes, which are associated with a generalized increase in mortality (but not with specific disease) would qualify as biomarkers of aging and would distinguish biological age from chronological age (passage of time). Because of increased average lifetime of people in the "western world", basic and clinical research in connection with aging and geriatrics has special importance in medicine. Better understanding of molecular and cellular mechanisms of aging could improve not only medical care of the elderly but could hold out also some hope in finding feasible solutions to slow down the aging process as well.

Estrogen therapy may counterbalance eutrophic remodeling of coronary arteries and increase bradykinin relaxation in a rat model of menopausal hypertension.

OBJECTIVE: Hypertension causes adverse remodeling and vasomotor alterations in coronaries. Hormones such as estrogen may help counterbalance some of these effects. The aim of this study was to analyze the effects of ovariectomy and estrogen therapy in a rat model of menopausal hypertension induced by angiotensin II (AII). METHODS: We investigated diameter, tone, and mechanics of intramural coronaries taken from ovariectomized female rats (n = 11) that received chronic AII treatment to induce hypertension, and compared the results with those found in female rats that were also given estrogen therapy (n = 11). The "hypertensive control" group (n = 11) underwent an abdominal sham operation, and received AII. After 4 weeks of AII treatment, side branches of left anterior descendent coronary (approximately 200 µm in diameter) were isolated, cannulated with plastic microcannulas at both ends, and studied in vitro in a vessel chamber. The inner and outer diameter of the arteries were measured by microangiometry, and spontenuous tone, wall thickness, wall cross-sectional area, tangential stress, incremental distensibility, circumferential incremental elastic modulus, thromboxane agonist-induced tone, and bradykinin-induced dilation were calculated. RESULTS: In hypertension, intramural small coronaries show inward eutrophic remodeling after ovariectomy comparing with hypertensive controls. Estrogen therapy had an opposite effect on vessel diameter. Hormone therapy led to an increase in spontaneous tone, allowing for greater dilatative capacity. CONCLUSIONS: Estrogen may therefore be considered to counterbalance some of the adverse changes seen in the wall of intramural coronaries in the early stages of chronic hypertension.

Effect of inhibitors of myeloperoxidase on the development of aortic atherosclerosis in an animal model.

Our earlier studies have shown that some steroids increase myeloperoxidase enzyme (MPO) release from human granulocytes, and that MPO plasma levels are significantly lower in postclimacteric people. Moreover, we have proven that MPO inhibits production of atherogenic free radical superoxide anion and MPO-inhibitors increase superoxide release. The aim of the present study was to investigate the effect of MPO-inhibitors on the early phase of aortic atherosclerosis, namely the extent of intimal plaques and the thickening of the medial layer. Adult male rabbits were fed with lipid rich food (cholesterol: 1.3%, peanut oil: 8%) for 8 weeks. During this period MPO-inhibitors were also given (4-aminobenzoicacid-hydrazide/ABAH/-13.3 mg/kg/day or indometacin-5 mg/kg/day). All animals developed intimal lipid plaques (raised fatty streaks). The relative plaque-covered areas of the aortas were compared and the media thickness of the aorta was measured on plaque-free as well as plaque-containing areas. The medial smooth muscle density and peroxidase activity of the aortic media were also determined. The media thickness increased (p<0.05) in the cholesterol+ABAH as well as in the cholesterol+indometacin groups up to 375.7 (+/-60.5) and 442.5 (+/-123.4) microm, respectively, compared to the control group (cholesterol feeding alone) where it measured only 308.4 (+/-51.67) microm. The medial peroxidase activity decreased significantly in the indometacin treated group and showed a decreasing tendency using ABAH. In parallel to this there was a tendency of increase in the relative plaque covered areas. The smooth muscle density showed no significant modifications, while inhibitors of the MPO seemed to enhance aortic medial thickness, i.e. the grade of a pre-atherosclerotic lesion, in our animal model. Collectively, the anti-atherogenic effect of certain steroid hormones might be realized through the impact on MPO activity.

Estrogen replacement therapy reverses changes in intramural coronary resistance arteries caused by female sex hormone depletion.

OBJECTIVE: We tested the hypothesis that female sex hormone depletion and estradiol replacement therapy significantly influences the biomechanical properties of intramural coronary resistance arteries. DESIGN: Female rats (n=30) were divided into three groups. In group O, rats were subjected to bilateral ovariectomy. Group HRT was subjected to bilateral ovariectomy and estradiol replacement therapy. Rats in group C served as controls. One month after ovariectomy, intramural coronary arteries (approximately 200 microm in diameter) branching from the left anterior descending coronary were isolated, cannulated and studied by microarteriography. Intraluminal pressure was increased in steps between 0 and 90 mm Hg. The steady state diameter at each step was measured. These measurements were repeated in the presence of U46619, a thromboxane (TX) A2 receptor agonist (at a concentration of 10(-6) M), and bradykinin (BK; at 10(-6) M). Finally, Ca2+-free Krebs-induced passive diameter (PD) was measured in each group. RESULTS: Ovariectomy increased spontaneous myogenic tone of coronary arteries (p<0.05), which was normalized by estrogen replacement. Ovariectomy decreased distensibility observed at low pressure, although passive diameter was not changed. Estrogen replacement decreased wall stress and elastic modulus (p<0.05). The thromboxane A2 agonist induced the largest contraction in the ovariectomized group, whereas bradykinin-induced relaxation was the largest in the estrogen replacement group (p<0.05). CONCLUSION: Estradiol hormone replacement therapy (HRT) may exert a beneficial effect on myocardial perfusion in menopause by opposing the deterioration of biomechanical properties of intramural coronary resistance vessels induced by female sex hormone depletion.

Sex hormone replacement therapy reverses altered venous contractility in rats after pharmacological ovariectomy.

OBJECTIVE: Female sex hormones have several important effects on the venous system. We earlier found that hormone replacement has a significant effect on venous distensibility, but effects of menopause and hormone replacement on venous contractility have never been studied. Therefore, and because the changes we found earlier in distensibility were most likely caused by alterations of contractility, we examined the changes in contractility of saphenous vein caused by depletion and replacement of sex hormones in female rats. DESIGN: Twenty Sprague-Dawley rats were pharmacologically ovariectomized by triptorelin. Ten of these rats received combined sex hormone replacement (HRT) with estradiol propionate and medroxyprogesterone acetate. The rest were given vehicle. Ten animals without ovariectomy served as controls. After 3 months of treatment, segments of the saphenous vein were dissected. Pressure-diameter curves were recorded in relaxed, contracted, and control states. RESULTS: Venous diameter, adjusted for body weight, was significantly decreased after pharmacological ovariectomy. HRT increased the diameter. The presence of sex hormones augmented norepinephrine contraction measured at physiological pressures (control: 19.2 +/- 2.3%; pharmacological ovariectomy: 15.2 +/- 1.4%, p < 0.05 and 17.8 +/- 2.2% following HRT). Myogenic (spontaneous) tone of the saphenous vein did not change after ovariectomy, but it was lowered by hormone replacement (control: 8 +/- 1.1%; ovariectomy: 6.9 +/- 2.5%; ovariectomy + HRT: 2.7 +/- 1.1%, p < 0.05). CONCLUSIONS: Sex hormone depletion induces significant alterations in contractility of the saphenous vein, which could perturb venous capacitance function and distensibility. This effect has a potential role in the development of hypertension and venous varicosity, and these changes could possibly be prevented by HRT.