Background and aimSuppression of poly(ADP-ribose) polymerase (PARP) activity, either PARP1 or PARP2, was proven to be beneficial in experimental colitis. The absence of PARP2 exclusively in T cells (T-PARP2-KO) was also shown recently to exert similar protection. Nevertheless, lower PARP1 expression in the intestines and reduced PARP activity in mononuclear cells from IBD patients were reported. Thus, we would like to investigate the effect of PARP2 deficiency in T cells superimposed on a PARP1 deletion background in the large intestines.MethodsDKO animals were generated from crossbreeding mice bearing single knockouts. The large intestines were examined by histopathology and various immune-based methods (immunohistochemistry, ELISA, and Western blot) to characterize the intestinal alterations through comparison with control and single knockout animals.ResultsThe DKO animals developed spontaneous intestinal inflammation in both the proximal and distal large intestines, reflected by both histological features and altered levels of the pro-inflammatory cytokine TNFα. In DKO animals, higher density of T cells and increased oxidative–nitrative stress were observed in the intestinal epithelium. Altered expression and activation of intracellular inflammatory signaling transduction proteins were found exclusively in the proximal segments, while the distal large intestines displayed elongated crypts despite the higher activation of caspase-3. The higher ratio of Ki-67-positive cells imply that the increased renewal of enterocytes is attributable to mucosal hyperplasia.ConclusionsPARPs may have essential roles in maintaining the integrity of large intestines, which are closely associated with lymphatic tissues. The combined genetic modification could potentially induce harmful alterations of the mucosa and the associated lymphatic tissue, leading to the occurrence of spontaneous inflammation with certain distinct segmental features.

Objective: Polycystic ovary syndrome (PCOS) represents the most prevalent endocrine disorder in women of fertile age; besides infertility, an elevated cardiovascular risk was described. Vitamin D hypovitaminosis affects about 80-90% of PCOS patients. Our team assessed aortic function and nitrative stress in a hyperandrogenic rat model and the effectiveness of Vitamin D substitution. Design and method: Female Wistar rats at the age of 3-4 weeks were randomly assigned into four groups. Eight rats received no treatment (controls, C), eight rats received weekly Vitamin D per os (140 IU/100 g body weight, group D), eight received cutaneous testosterone daily (3.3 mg/100 g, T) and eight received Vitamin D and testosterone (T+D). At the eighth week of the treatment, aortic rings were isolated for analysis: they were cut into 3-4 mm long segments for myography, other segments were formaldehyde fixed and paraffin embedded to assess, by immunohistochemical methods, nitrative stress markers (nitrotyrosine, NT) and DNA breaks signaled by nuclear poly(ADP-ribose) polymer (PAR) detection. Results: The weight gains of the two testosterone-treated groups were significantly higher between the 6-8 weeks compared to the other two groups, Vitamin D treatment did not influence body weight. Rats in the C and D groups had 3 or 4 estruses in the last 14 days. T rats had 1 or 2 estruses during the same period. T+D rats had 1-2 (N=3), or 3-4 (N=5) estruses. Aortic contraction, induced by the alpha1-adrenergic agonist phenylephrine, was significantly elevated in T and T+D animals in comparison to controls and Vitamin D treated rats. The endothelium-mediated aortic relaxation, as a response to acetyl-choline and insulin, was unaltered; however, estrogen-induced relaxation was significantly impaired in T and T+D groups. According to resorcin-fuchsin staining, no fibrotic alteration was detected. Nitrative stress and poly(ADP-ribosyl)ation were similar in all four groups. Conclusions: Eight weeks of testosterone administration caused increased weight gain and sex cycle lengthening. The latter was reversible by Vitamin D supplementation in 62.5% of the rats. Testosterone or Vitamin D did not alter vascular histology. Hyperandrogenism increased alpha1-adrenerg mediated vasoconstriction and compromised estrogen-mediated relaxation without altering nitrative stress.

Objective: Polycystic ovary syndrome (PCOS) is a common gynecological disorder of endocrine origin that can be associated with increased cardiovascular morbidity and vitamin D deficiency. The effects of vitamin D deficiency on cardio-metabolic risk in PCOS have been shown in previous studies. In the present experiments, we investigated the effect of vitamin D supplementation in light of optimal vitamin D intake on rat carotid artery function in a rat model of PCOS. Our aim was to investigate the effects of vitamin D supplementation and hyperandrogenism on functional and morphological changes of the carotid artery. Design and method: Adolescent female Wistar rats were provided with normal (C: 1000 IU/day/kg/week) or increased (D: 3000 IU/day/kg/week) vitamin D intake for 8 weeks. In half of these animals hyperandrogenism was induced by testosterone treatment (T and T+D: daily cutaneous testosterone: 3.3 mg/100 g) (N=8 in all 4 groups). After 8 weeks, carotid arteries were isolated and phenylephrine (Phe)-induced contraction and acetylcholine (Ach)-induced relaxation of the vascular rings were examined by myography. Wall thickness and intima-media ratio were determined in hematoxylin-eosin stained tissue sections, vessel wall connective tissue fiber density in resorcin-fuchsin stained sections, and vessel smooth muscle densitometry by -αsmooth muscle actin immunostaining. Results: The hyperandrogenic state induced a decreased contractility as a response to Phe (10-6 M Phe expressed in the % of K+-induced contraction: T: 62±22% p<0.001 vs. C: 116±33%; D: 101±39%), that was reversible by Vitamin D treatment (T+D: 95±16%, ns.). Endothelium-mediated relaxation did not differ between groups. Hyperandrogenic state significantly increased vessel wall thickness (T: 74.81 ±4.48 μm, p<0.05 vs. C: 57.92±2.96 μm; D: 53.21±10.8 μm), which was prevented by Vitamin D (58.99±8.75 μm, ns.) whereas intima-media ratio did not change. No significant differences were found for smooth muscle actin and connective tissue fiber density. Conclusions: Our results suggest that the hyperandrogenism increased vessel wall thickness and, in comparison to media thickness the alpha1-adrenerg sensitivity decreased, leading to a limited capacity of regulation. The morphological remodeling of the vascular wall induced by testosterone treatment did not cause significant endothelial functional changes yet.

Objective: Polycystic ovary syndrome (PCOS), a prevalent endocrine disorder in women, is associated with elevated cardiovascular risk and vitamin D deficiency. This study evaluates blood pressure, renal arterial function and oxidative stress in a rat PCOS model, also exploring the impact of vitamin D supplementation. Assessing mean arterial blood pressure under anesthesia, renal arterial function and oxidative stress in a hyperandrogenic rat model, and the effectiveness of vitamin D substitution. Design and method: Thirty-two adolescent female Wistar rats were randomly assigned into four groups. Eight rats received no treatment (controls, C), eight received weekly Vitamin D per os (140 IU/100 g body weight, group D), eight received cutaneous testosterone daily (3.3 mg/100 g, T), and eight received Vitamin D and testosterone together (T+D). In the eighth week of the treatment, rats were anaesthetized with urethane, and blood pressure (MABP) was measured. The isolated renal arterial rings were cut into 3-4 mm long segments for wire myography. Other segments were formaldehyde-fixed and paraffin-embedded for histological evaluations. By immunohistochemical methods, we assessed the oxidative stress marker 4-hydroxynoneal (HNE) and poly(ADP-ribose) polymerase activation shown by nuclear poly(ADP-ribose) polymer (PAR). Results: MABP was lower in hyperandrogenic rats, which was not altered by Vitamin D supplementation. Phenylephrine-induced contraction (Phe) in 10-9-10-7 M concentrations was identical in all groups; however, 10-6 M Phe caused a lower contraction in D and T rats (54.4± 21% and 41.9±20% vs. C: 72.78±8% and T+D: 69.68±21%. p<0.05) compared to controls and double treated animals. Endothelium-mediated relaxation did not differ between groups. PAR staining was also identical, but HNE staining showed a tendency for increment in group T (p=0.12) but not in T+D. Conclusions: The decreased mean arterial pressure is likely the result of the compromised sensitivity to alpha1-adrenergic stimulus. The reduced reactivity of the renal artery may influence the activity of the renin-angiotensin-aldosterone system (RAAS). By normalizing the phenylephrine-induced contraction, Vitamin D supplementation might restore RAAS, thus blood pressure regulation.

Introduction T cell-dependent inflammatory response with the upregulation of helper 17 T cells (Th17) and the downregulation of regulatory T cells (Treg) accompanied by the increased production of tumor necrosis alpha (TNFa) is characteristic of inflammatory bowel diseases (IBD). Modulation of T cell response may alleviate the inflammation thus reduce intestinal damage. Poly(ADP-ribose) polymerase-2 (PARP2) plays role in the development, differentiation and reactivity of T cell subpopulations. Our aim was to investigate the potential beneficial effect of T cell-specific PARP2 downregulation in the lipopolysaccharide (LPS) induced inflammatory response of the cecum and the colon. Methods Low-dose LPS was injected intraperitoneally to induce local inflammatory response, characterized by increased TNFa production, in control (CD4Cre; PARP2+/+) and T cell-specific conditional PARP2 knockout (CD4Cre; PARP2f/f) mice. TNFa, IL-1b, IL-17 levels were measured by ELISA, oxidative–nitrative stress was estimated by immunohistochemistry, while PARP1 activity, p38 MAPK and ERK phosphorylation, and NF-kB expression in large intestine tissue samples were examined by Western-blot. Systemic & local T cell subpopulation; Th17 and Treg alterations were also investigated using flowcytometry and immunohistochemistry. Results In control animals, LPS induced intestinal inflammation with increased TNFa production, while no significant elevation of TNFa production was observed in T cell-specific PARP2 knockout animals. The absence of LPS-induced elevation in TNFa levels was accompanied by the absence of IL-1b elevation and the suppression of IL-17 production, showing markedly reduced inflammatory response. The increase in oxidative-nitrative stress and PARP1-activation was also absent in these tissues together with altered ERK and NF-kB activation. An increase in the number of the anti-inflammatory Treg cells in the intestinal mucosa was observed in these animals, together with the reduction of Treg count in the peripheral circulation. Discussion Our results confirmed that T cell-specific PARP2 downregulation ameliorated LPS-induced colitis. The dampened TNFa production, decreased IL-17 production and the increased intestinal regulatory T cell number after LPS treatment may be also beneficial during inflammatory processes seen in IBD. By reducing oxidative-nitrative stress and PARP1 activation, T cell-specific PARP2 downregulation may also alleviate intestinal tissue damage.

In endotoxemic models, the inflammatory parameters are altered to a favorable direction as a response to activation of cannabinoid receptors 1 and 2. The phytocannabinoid Δ9-tetrahydrocannabinol (THC) is an agonist/partial antagonist of both cannabinoid receptors. This report targets the effects of THC on the cardiovascular system of endotoxemic rats. In our 24-hour endotoxemic rat model (E. coli derived lipopolysaccharide, LPS i.v. 5mg/kg) with THC treatment (LPS+THC 10 mg/kg i.p.), we investigated cardiac function by echocariography and endothelium-dependent relaxation of the thoracic aorta by isometric force measurement compared to vehicle controls. To evaluate the molecular mechanism, we measured endothelial NOS and COX-2 density by immunohistochemistry; and determined the levels of cGMP, the oxidative stress marker 4-hydroxynonenal, the nitrative stress marker 3-nitrotyrosine, and poly(ADP-ribose) polymers. A decrease in end-systolic and end-diastolic ventricular volumes in the LPS group was observed, which was absent in LPS+THC animals. Endothelium-dependent relaxation was worsened by LPS but not in the LPS+THC group. LPS administration decreased the abundance of cannabinoid receptors. Oxidative-nitrative stress markers showed an increment, and cGMP, eNOS staining showed a decrement in response to LPS. THC only decreased the oxidative-nitrative stress but had no effect on cGMP and eNOS density. COX-2 staining was reduced by THC. We hypothesize that the reduced diastolic filling in the LPS group is a consequence of vascular dysfunction, preventable by THC. The mechanism of action of THC is not based on its local effect on aortic NO homeostasis. The reduced oxidative-nitrative stress and the COX-2 suggest the activation of an anti-inflammatory pathway.

Objective: Polycystic ovary syndrome (PCOS) and vitamin D deficiency are associated with elevated cardiovascular risk, whereas vitamin D deficiency is a common comorbidity in PCOS that may contribute to the pathogenesis and complications of the disease. Our aim was to investigate the role of vitamin D status on the aortic function of hyperandrogenic female rats showing the symptoms of PCOS. Design and method: Female Wistar rats received an 8-week-long transdermal Androgel treatment to induce hyperandrogenism, another group remained untreated. Half of each group was fed with vitamin D reduced rat chow, while the other half received normal chow with further supplementation of vitamin D. Norepinephrine-induced contraction, acetylcholine, insulin, and estrogen-induced relaxation of thoracic aortae was examined by wire myography. Elastic fiber density was evaluated on resorcin-fuchsin stained tissue sections. Estrogen receptor alpha, endothelial nitric oxide synthase (eNOS), and cyclooxygenase 2 (COX-2) density and protein tyrosine nitration (NT) was measured by immunohistochemistry. Results: There was no difference in the norepinephrine-induced contraction of the aortas between experimental groups. Reduced acetylcholine-, insulin- and estrogen-evoked relaxation was observed in vitamin D deficient groups. A lower level of resorcin-fuchsin staining and elevated 3- nitrotyrosine immunostaining was observed in non-hyperandrogenic vitamin D deficient rats. eNOS staining intensity was reduced by vitamin D deficiency, while COX-2 density was increased by testosterone treatment. Estrogen receptor alpha density was increased by testosterone treatment but reduced by vitamin D deficiency. Conclusions: We demonstrated an early endothelial dysfunction in a rat model of vitamin D deficient polycystic ovary syndrome. Vitamin D supplementation could prevent vascular damage. On the other hand, vitamin D deficiency itself led to decreased endothelium-dependent relaxation and increased nitrative stress. Vitamin D deficiency also led to decreased estrogen receptor alpha and eNOS density independently from hyperandrogenism. Vitamin D deficiency found in approximately 80% of PCOS women may have a significant role in the development of vascular dysfunction and may contribute to their increased cardiovascular risk.

Background: Vitamin D deficiency (VDD) may be considered an independent cardiovascular (CV) risk factor, and it is well known that CV risk is higher in males. Our goal was to investigate the pharmacological reactivity and receptor expression of intramural coronary artery segments of male rats in cases of different vitamin D supply. Methods: Four-week-old male Wistar rats were divided into a control group (n = 11) with optimal vitamin D supply (300 IU/kgbw/day) and a VDD group (n = 11, <0.5 IU/kgbw/day). After 8 weeks of treatment, intramural coronary artery segments were microprepared, their pharmacological reactivity was examined by in vitro microangiometry, and their receptor expression was investigated by immunohistochemistry. Results: Thromboxane A2 (TXA2)-agonist induced reduced vasoconstriction, testosterone (T) and 17-β-estradiol (E2) relaxations were significantly decreased, a significant decrease in thromboxane receptor (TP) expression was shown, and the reduction in estrogen receptor-α (ERα) expression was on the border of significance in the VDD group. Conclusions: VD-deficient male coronary arteries showed deteriorated pharmacological reactivity to TXA2 and sexual steroids (E2, T). Insufficient vasoconstrictor capacity was accompanied by decreased TP receptor expression, and vasodilator impairments were mainly functional. The decrease in vasoconstrictor and vasodilator responses results in narrowed adaptational range of coronaries, causing inadequate coronary perfusion that might contribute to the increased CV risk in VDD.

BACKGROUND:The cardiovascular effects of training have been widely investigated; however, few studies have addressed sex differences in arteriolar adaptation. In the current study, we examined the adaptation of the gracilis arterioles of male and female rats in response to intensive training.METHODS:Wistar rats were divided into four groups: male exercise (ME) and female exercise (FE) animals that underwent a 12-week intensive swim-training program (5 days/week, 200 min/day); and male control (MC) and female control (FC) animals that were placed in water for 5 min daily. Exercise-induced cardiac hypertrophy was confirmed by echocardiography. Following the training, the gracilis muscle arterioles were prepared, and their biomechanical properties and functional reactivity were tested, using pressure arteriography. Collagen and smooth muscle remodeling were observed in the histological sections.RESULTS:Left ventricular mass was elevated in both sexes in response to chronic training. In the gracilis arterioles, the inner radius and wall tension increased in female animals, and the wall thickness and elastic modulus were reduced in males. Myogenic tone was reduced in the ME group, whereas norepinephrine-induced vasoconstriction was elevated in the FE group. More pronounced collagen staining was observed in the ME group than in the MC group. Relative hypertrophy and tangential stress of the gracilis arterioles were higher in females than in males. The direct vasoconstriction induced by testosterone was lower in females and was reduced as an effect of exercise in males.CONCLUSION:The gracilis muscle arteriole was remodeled as a result of swim training, and this adaptation was sex dependent.

We examined the vasoactive effect of estradiol in a rat model of early PCOS and the influence of vitamin D deficiency (VDD). We created a model of chronic hyperandrogenism and VDD in adolescent female Wistar rats (N = 46) with four experimental groups: vitamin D supplemented (T-D+), VDD (T-D-), hyperandrogenic and vitamin D supplemented (T+D+), and hyperandrogenic and VDD (T+D-). T+ groups received an 8-week-long transdermal Androgel treatment, D-animals were on vitamin D-reduced diet and D+ rats were supplemented orally with vitamin D3. Estrogen-induced vasorelaxation of thoracic aorta segments were measured with a wire myograph system with or without the inhibition of endothelial nitric oxide synthase (eNOS) or cyclooxygenase-2 (COX-2). The distribution of estrogen receptor (ER), eNOS and COX-2 in the aortic wall was assessed by immunohistochemistry. VDD aortas showed significantly lower estradiol-induced relaxation independently of androgenic status that was further decreased by COX-2 inhibition. COX-2 inhibition failed to alter vessel function in D+ rats. Inhibition of eNOS abolished the estradiol-induced relaxation in all groups. Changes in vascular function in VDD were accompanied by significantly decreased ER and eNOS staining. Short-term chronic hyperandrogenism failed to, but VDD induced vascular dysfunction, compromised estrogen-dependent vasodilatation and changes in ER and eNOS immunostaining.

Heart transplantation remains the definitive therapy of end-stage heart failure. Ischemia-reperfusion injury occurring during transplantation is a primary determinant of long-term outcome of heart transplantation and primary graft insufficiency. Modification of the nitric oxide/soluble guanylate cyclase/cyclic guanosine monophosphate signaling pathway appears to be one of the most promising among the pharmacological interventional options. We aimed at characterizing the cardio-protective effects of the soluble guanylate cyclase stimulator riociguat in a rat model of heterotopic heart transplantation. Donor Lewis rats were treated orally with either riociguat or placebo for two days (n = 9) in each transplanted group and (n = 7) in donor groups. Following explantation, hearts were heterotopically transplanted. After one hour reperfusion, left ventricular pressure-volume relations and coronary blood flow were recorded. Molecular biological measurements and histological examination were also completed. Left ventricular contractility (systolic pressure: 117 ± 13 vs. 48 ± 5 mmHg, p < 0.001; dP/dt max : 2963 ± 221 vs. 1653 ± 159 mmHg/s, p < 0.001), active relaxation (dP/dt min : −2014 ± 305 vs. −1063 ± 177 mmHg/s, p = 0.02; all at 120 µl of left ventricular volume), and alteration of coronary blood flow standardized to heart weight (2.55 ± 0.32 vs. 1.67 ± 0.22 ml/min/g, p = 0.03) were markedly increased following preconditioning with riociguat. Myocardial apoptosis markers were also significantly reduced in the riociguat pretreated group as well as the antioxidant markers were elevated. Pharmacological preconditioning with riociguat decreases ischemia-reperfusion injury and improves donor organ function in our animal model of heart transplantation. Therefore, riociguat might be a potential cardioprotective agent.

Bevezetés: A nátrium-glükóz-kotranszporter-2-(SGLT2) inhibitor canagliflozin csökkenti a 2-es típusú diabéteszes betegekben a súlyos kardiovaszkuláris események előfordulását.Ez direkt kardiovaszkuláris hatásra utalhat, amely jelenleg nem teljesen tisztázott.Célul tűztük ki a canagliflozin kardiovaszkuláris hatásainak karakterizálását

Background: Several reports prove interconnection between vitamin D (VD) deficiency and increased cardiovascular risk. Our aim was to investigate the effects of VD status on biomechanical and oxidative–nitrative (O–N) stress parameters of coronary arterioles in rats. Methods: 4-week-old male Wistar rats were divided into a control group (11 animals) with optimal VD supply (300 IU/kgbw/day) and a VD-deficient group (11 animals, <5 IU/kg/day). After 8 weeks, coronary arteriole segments were prepared. Geometrical, elastic, and biomechanical characteristics were measured by in vitro arteriography. O–N stress markers were investigated by immunohistochemistry. Results: Inner radius decreased; wall thickness and wall-thickness/lumen diameter ratio increased; tangential wall stress and elastic modulus were reduced in VD-deficient group. No difference could be found in wall-cross-sectional area, intima-media area %. While the elastic elements of the vessel wall decreased, the α-smooth muscle actin (α-SMA) immunostaining intensity showed no changes. Significant elevation was found in the lipid peroxidation marker of 4-hidroxy-2-nonenal (HNE), while other O–N stress markers staining intensity (poly(ADP)ribose, 3-nitrotyrosine) did not change. Conclusions: Inward eutrophic remodeling has developed. The potential background of these impairments may involve the initial change in oxidative damage markers (HNE). These mechanisms can contribute to the increased incidence of the cardiovascular diseases in VD deficiency.

In the 16th-17th century, many libertines hid their thoughts by obscuring their ideas and mixing old and new theories. Cyrano’s method may open a window to the methods of early modern thinkers’ ways to conceal heretic ideas. I analysed 16th and 17th century biology and modern-day understanding of the human mind to assess how Cyrano described the works of the brain, predominantly in his novels. His writings open a window into the early modern understanding of biology as well as to some new concepts of his, including probably the first investigation on twins resulting in a description of empathy as a motor function. An analysis of recent data about mental decline in the elderly in relation to his father’s words allows the consideration of their relationship. Le Combat de Cyrano de Bergerac avec le singe de Brioché, au bout du Pont-Neuf of d’Assoucy’s may give a peek into the young Cyrano’s dangerous tendencies and a portrayal of the famous battle at the Porte de Nesle.

In polycystic ovary syndrome (PCOS) hyperandrogenism and metabolic dysfunction increase cardiovascular risk. Vitamin D3 deficiency is a common comorbidity in PCOS. Our aim was to examine the alterations of insulin-induced vasodilation and receptor expression in rat aorta in a PCOS model. Methods: Female Wistar rats were treated as follows: 1. vitamin D supplemented group (D+T−); 2. vitamin D deficient (D−T−), 3. vitamin D supplemented with transdermal testosterone application (D+T+) and 4. vitamin D deficient with transdermal testosterone (D−T+). Wire myograph was used for testing insulin relaxation of aorta rings in physiological salt solution and under NOS inhibition. Insulin (IR) and vitamin D receptor (VDR) density was examined by immunohistochemistry. Results: Insulin-induced vasodilatation of the aorta rings were significantly lower in both vitamin deficient compared to the vitamin supplemented groups (p < 0.05). NOS inhibition significantly reduce the relaxation. Aorta endothelial IR expression was significantly higher in the vitamin D deficient group, meanwhile in the testosterone-treated groups (D+T+; D−T+) the expression was significantly lower (Area%: D+: 0.830 ± 0.10; D+T+: 0.298 ± 0.06; D−: 1.364 ± 0.12; D−T+: 0.354 ± 0.15, p < 0.05 in D− & D+T+ & D−T+ vs D+. p < 0.01 D+T+ & D−T+ vs D−). VDR density was significantly higher in the vitamin D deficient groups in comparison to the supplemented groups (Area% VDR: D+: 41.56 ± 5.58 vs D−: 60.63 ± 5.23) Testosterone treatment have not any effect on VDR expression. Conclusion: Vitamin-D deficiency causes impaired insulin induced vasodilation. Increased IR density could not compensate altered insulin-induced relaxation.

Objectives: The cardiovascular/CV risk is higher in males. To know better these increased risks, our aim was to investigate the effects of different vitamin D/VD status on mechanical, pharmacological and histological characteristics of coronary arterioles in male rat model. Methods: In male Wistar-rats we induced different VD status: “Group C” got 1000 IU VD containing rat chow and VD-supplementation, “Group D-” got less, than 5 IU VD containing rat chow to model the VD deficient/VDD status. At the end of the experiment we prepared intramural, small coronary arteriole segments from the LAD. With microangiometer, we measured the inner and outer diameters, TXA2-vasoconstriction, adenosine-vasorelaxation, and the passive diameter. Histopathological examinations were taken. Results: Inner and outer radius were significantly decreased, wall thickness and wall-thickness/lumen diameter ratio were significantly increased in group D-, while the wall-cross-sectional area and the intima-media area% were not different. Tangential wall stress and incremental elastic modulus were significantly reduced in group D-. TXA2-vasoconstriction significantly lower in group D-. In the point of adenosine-induced vasorelaxation, in group D-only the highest dose of adenosine could relax the vessels. eNOS-expression was not differ, SMA-expression was significantly decreased in group D-. Conclusion: The characteristics of the VDD group’s coronary arterioles had changed. The results refer to development of inner eutrophic remodelling and changed wall structure. These changes can cause increased vascular resistance and diminished coronary perfusion which as a result lead to the deterioration of the heart’s blood supply. These mechanisms can contribute to the increased incidence of the CV diseases in VDD.

Vitamin D (vitD) insufficiency affects 1 billion people worldwide. Androgen excess (AE) occurs in 8% of fertile females. There are few data about the combined effect of vitD deficiency and AE on the early biomechanical changes of cerebral arterioles in fertile-aged female. Forty-six adolescent female Wistar rats (21-28 day-old, weighing 90-110 g) were grouped randomly in four groups: vitD supplemented groups with and without transdermal testosterone (T) treatment, as well as vitD deficient groups also with and without transdermal T (n = 11 or 12, in all cases). After 8 weeks of treatment, anterior cerebral arterioles (in vivo diameter of 90-130 mu m) were obtained and cylindrical segments were examined by pressure arteriography. Myogenic tone, tangential stress and incremental elastic moduli were computed and statistically analyzed. Elastic density was studied on resorcin-fuchsin-stained histological section. VitD deficiency with T treatment resulted in significantly lower inner radii and higher wall thickness values with reduced tangential stress and increased elastic fiber density. VitD deficiency reduced myogenic tone at higher intraluminar pressures (>110 mmHg). Our conclusion is that plasma vitD level is an important factor in the control of myogenic tone in cerebral resistance arteries. AE and vitD deficiency acting parallel induce remodeling of their wall.