Cardiovascular complications and increased levels of circulating modified low density lipoprotein in HIV patients and patients with lipodystrophy

The introduction of highly active antiretroviral therapy (HAART) for patients infected with HIV has significantly prolonged the life expectancy and to some extent has restored a functional immune response. However, the premature introduction of HAART has led to a significant and alarming increase in cardiovascular complications, including myocardial infarction and the appearance of abnormal distribution of body fat seen as lipodystrophy. One key element in the development of ischemic coronary artery disease is the presence of circulating and tissue-fixed modified low density lipoprotein (mLDL) that contributes to the initiation and progression of arterial lesions and to the formation of foam cells. Even though not completely elucidated, the most likely mechanism involves mLDL in the inflammatory response and the induction of a specific immune response against mLDL. Circulating antibodies against mLDL can serve as an indirect marker of the presence of circulating and vessel-fixed mLDL. In the present study, we measured antibodies to mLDL and correlated them with immune status (i.e., number of CD4+ T cells) in 59 HIV patients and with the clinical manifestation of lipodystrophy in 10 patients. We observed a significant reduction in anti-mLDL antibody levels related both to lipodystrophy and to an immunocompromised state in HIV patients. We speculate that these antibodies may explain in part the rapid development of ischemic coronary artery disease in some patients.

Compensatory enlargement of human coronary arteries identified by magnetic resonance imaging

The aim of the present study was to evaluate the role of magnetic resonance imaging (MRI) for the non-invasive detection of coronary abnormalities and specifically the remodeling process in patients with coronary artery disease (CAD). MRI was performed in 10 control healthy subjects and 26 patients with angiographically proven CAD of the right coronary (RCA) or left anterior descending (LAD) artery; 23 patients were within two months of acute coronary syndromes, and 3 had stable angina with a positive test for ischemia. Wall thickness (WT), vessel wall area (VWA), total vessel area (TVA), and luminal area (LA) were measured. There were significant increases in WT (mean ± SEM, RCA: 2.62 ± 0.75 vs 0.53 ± 0.15 mm; LAD: 2.21 ± 0.69 vs 0.62 ± 0.24 mm) and in VWA (RCA: 30.96 ± 17.57 vs 2.1 ± 1.2 mm²; LAD: 19.53 ± 7.25 vs 3.6 ± 2.0 mm²) patients compared to controls (P < 0.001 for each variable). TVA values were also greater in patients compared to controls (RCA: 44.56 ± 21.87 vs 12.3 ± 4.2 mm²; LAD: 31.89 ± 11.31 vs 17.0 ± 6.2 mm²; P < 0.001). In contrast, the LA did not differ between patients and controls for RCA or LAD. When the LA was adjusted for vessel size using the LA/TVA ratio, a significant difference was found: 0.33 ± 0.16 in patients vs 0.82 ± 0.09 in controls (RCA) and 0.38 ± 0.13 vs 0.78 ± 0.06 (LAD) (P < 0.001). As opposed to normal controls, positive remodeling was present in all patients with CAD, as indicated by larger VWA. We conclude that MRI detected vessel wall abnormalities and was an effective tool for the noninvasive evaluation of the atherosclerotic process and coronary vessel wall modifications, including positive remodeling that frequently occurs in patients with acute coronary syndromes.

Intracranial Nimodipine Implant: Feasibility and Implications for the Treatment of Subarachnoid Hemorrhage – A Pre-Clinical Study

Intracranial aneurysmal subarachnoid hemorrhage (aSAH) is a life-threatening condition requiring immediate neurocritical care. A ruptured aneurysm must be isolated from arterial circulation to prevent rebleeding. Open surgical clipping of the neck of the aneurysm or intra-arterial filling of the aneurysm sack with platinum coils are major treatment strategies in an acute phase. About 40% of the patients suffering from aSAH die within a year of the bleeding despite the intensive treatment. After aSAH, the patient may develop a serious complication called vasospasm. Major risk for the vasospasm takes place at days 5–14 after the primary bleeding. In vasospasm, cerebral arteries contract uncontrollably causing brain ischemia that may lead to death. Nimodipine (NDP) is used to treat of vasospasm and it is administrated intravenously or orally every four hours for 21 days. NDP treatment has been scientifically proven to improve patients’ clinical outcome. The therapeutic effect of L-type calcium channel blocker NDP is due to the ability to dilate cerebral arteries. In addition to vasodilatation, recent research has shown the pleiotropic effect of NDP such as inhibition of neuronal apoptosis and inhibition of microthrombi formation. Indeed, NDP inhibits cortical spreading ischemia. Knowledge of the pathophysiology of the vasospasm has evolved in recent years to a complex entity of early brain injury, secondary injuries and cortical spreading ischemia, instead of being pure intracranial vessel spasm. High NDP levels are beneficial since they protect neurons and inhibit the cortical spreading ischemia. One of the drawbacks of the intravenous or oral administration of NPD is systemic hypotension, which is harmful particularly when the brain is injured. Maximizing the beneficial effects and avoiding systemic hypotension of NDP, we developed a sustained release biodegradable NDP implant that was surgically positioned in the basal cistern of animal models (dog and pig). Higher concentrations were achieved locally and lower concentrations systemically. Using this treatment approach in humans, it may be possible to reduce incidence of harmful hypotension and potentiate beneficial effects of NDP on neurons. Intracellular calcium regulation has a pivotal role in brain plasticity. NDP blocks L-type calcium channels in neurons, substantially decreasing intracellular calcium levels. Thus, we were interested in how NDP affects brain plasticity and tested the hypothesis in a mouse model. We found that NDP activates Brain-derived neurotrophic factor (BDNF) receptor TrkB and its downstream signaling in a reminiscent of antidepressant drugs. In contrast to antidepressant drugs, NDP activates Akt, a major survival-promoting factor. Our group’s previous findings demonstrate that long-term antidepressant treatment reactivates developmental-type of plasticity mechanisms in the adult brain, which allows the remodeling of neuronal networks if combined with appropriate rehabilitation. It seems that NDP has antidepressant-like properties and it is able to induce neuronal plasticity. In general, drug induced neuronal plasticity has a huge potential in neurorehabilitation and more studies are warranted.

131I-induced changes in rat thyroid gland function

Therapeutic doses of 131I administered to thyrotoxic patients may cause thyroid failure. The present study used a rat model to determine thyroid function after the administration of different doses of 131I (64-277 µCi). Thirty male Fisher rats in the experimental group and 30 in the control group (untreated) were followed for 6 months. The animals were 4 months old at the beginning of the experiment and were sacrificed at an age of 9 months. Hormone concentration was determined before 131I administration (4-month-old animals) and three times following 131I administration, when the animals were 7, 8, and 9 months old. The thyroid glands were removed and weighed, their volume was determined and histopathological examination was performed at the end of the experiment. Significant differences in serum triiodothyronine and thyroid-stimulating hormone concentration, measured at the age of 7, 8, and 9 months, were found in the experimental group. During aging of the animals, the concentration of thyroxin fell from 64.8 ± 8.16 to 55.0 ± 6.1 nM in the control group and from 69.4 ± 6.9 to 25.4 ± 3.2 nM in the experimental group. Thyroid gland volume and weight were significantly lower in the experimental than in the control group. Thyroid glands from the experimental group showed hyaline thickness of the blood vessel wall, necrotic follicles, a strong inflammatory reaction, and peeling of necrotic cells in the follicles. In conclusion, significant differences in hormone levels and histopathological findings indicated prolonged hypothyroidism after 131I administration to rats, which was not 131I dose dependent.

Postimerkit merisotataidon dokumentteina : Britannian ja Saksan laivastojen varustelu maailmansotien välisenä aikana

Merisodassa tapahtunut muutos – erityisesti konevoiman syrjäyttäessä purjeet ja raudan korvatessa puumateriaalin 1800-luvun loppupuolella – johti nykypäivänäkin merkittäviin merisodan teoreettisiin tarkasteluihin. Teorioihin pohjautuneet merisotataidon yleisperiaatteet saivat ensimmäisen maailmansodan aikana käytännön testauksensa. Voittajat ja häviäjät analysoivat taistelut sekä maailmalla vallinneen ripeän teknisen kehityksen, minkä seurauksena laivastojen varustelu kiihtyi uudestaan valtapolitiikan tueksi. Maailmansotien välisenä aikana pyrittiin kansainvälisin sopimuksin säätelemään suurten laivastojen, kuten Britannian, Ranskan, Italian, Japanin ja Yhdysvaltojen varustelukilpailua. Versaillesin rauhansopimus rajoitti samanaikaisesti Saksan merivoimien kokoa. Tässä työssä tutkitaan Britannian ja Saksan merivoimien varustelua ja merisotataidon kehittymistä maailmansotien välisenä aikana. Merisotataidon kehittymisen tarkastelu tapahtuu postimerkkien avulla. Postimerkki syntyi Englannissa vuonna 1840 ja sen käyttö yleistyi ympäri maailman lähes samanaikaisesti konevoimaa käyttäneiden laivojen kanssa. Postimerkkien kuva-aiheet olivat aluksi valtioiden päämiehiä, heraldiikkaa, maisemia tai abstrakteja aiheita. Vasta 1900-luvun alkupuolella kuva-aiheina saattoi olla lähes mitä vain, myös sotalaivojen kuvia. Postimerkkikokoelmastani erottuu tutkimusaiheeseen 335 merkkiä. Britannian ja Saksan kansallisarkistojen alkuperäislähteiden ja tutkimuskirjallisuuden dokumenttianalyysiin perustuvaa merisotataidon moninaista kehitystä verrataan tutkimuksessani postimerkkien kuva-aiheisiin ja niiden yksityiskohtiin 3 300 kertaa. Tällä menettelyllä pyrin selvittämään voiko postimerkkejä käyttää ja pitää merisotaidon kehityksen kattavina dokumentteina. Postimerkeissä satunnaisiksi jääneet virheet tai propaganda eivät vähennä merisotataidon kehityksen kuvaamisen dokumenttiarvoa. Postimerkkien sotalaivoihin liittyvät kuvat kattavat muutamaa laivaluokkaa lukuunottamatta molempien maiden kaikki taistelualuslajit- ja luokat. Postimerkeistä voidaan nähdä vanhat sotalaivat, niiden peruskorjaukset ja uudet luokat lentotukialuksista sukellusveneisiin. Alusten kuvat voidaan liittää Britannian kansainyhteisön muuttuneisiin strategisiin ja taktisiin tavoitteisiin niin Atlantilla kuin Kaukoidässä. Saksan merivoimien nousu Versaillesin rauhanehtojen rajoituksista ja lopulta pyrkimys Britannian kauppamerenkulun tuhoajaksi välittyy myös postimerkeistä. Yleinen sotatekninen kehitys, lentoneiden tulo merisotanäyttämölle ja aikanaan kansainvälisten tonnistorajoitusten poistuminen näkyvät postimerkeissä. Kokopostimerkin historian aikana vuoteen 2012 mennessä purjeettomien, nykyaikaisten sotalaivojen kuvia on julkaistu noin 3 350 postimerkillä, jotka on koottu Maailman suurin laivasto-osasto -postimerkkikokoelmaani noin 35 vuoden aikana

Ydinvoimalaitos AES-2006:n reaktorin painesäiliön rakenne, materiaalivalinta, valmistustekniikka ja asennus

Tässä kandidaattityössä on käsitelty Rusatom Overseas Oy:n toimittaman ydinvoimalaitoksen AES-2006 reaktoripiiriin kuuluvan painesäiliön ominaisuuksia, materiaalivalintoja ja niiden kriteerejä, reaktorin valmistusmenettelyä ja sen asennusvaiheita mukaan lukien pääkiertoputkiston hitsaus julkisesti saatavilla olevan materiaalin pohjalta. Tässä kandidaatintyössä on kuvattu AES-2006 ydinvoimalaitoksen kehityshistoria ja lueteltu sen keskeisimmät eroavuudet edeltäjistään. Työn keskeisessä osassa on tarkastettu VVER-1200 reaktorin painesäiliön toimittajan ilmoittaman teräksen koostumus ja tärkeimpien seosaineiden vaikutus painesäiliöön ja koko voimalaitoksen käyttöikään. Tämän jälkeen on käsitelty reaktorin painesäiliön valmistustekniikkaa ja asennusta reaktorirakennuksessa. Johtopäätöksissä on vedetty yhteen tulokset ja otettu kantaa vertailukelpoiseen painesäiliöteräkseen ja sen ominaisuuksiin. Tärkeimmiksi seikoiksi nousevat tässä työssä seosaineiden myönteinen ja kielteinen vaikutus koko ydinvoimalaitoksen käyttöikään, ja ko. seosaineiden hallinnan tärkeys valmistus- ja asennusvaiheissa.

Differences in functional and structural properties of segments of the rat tail artery

The investigation of resistance vessels is generally costly and difficult to execute. The present study investigated the diameters and the vascular reactivity of different segments of the rat tail artery (base, middle, and tail end) of 30 male Wister rats (EPM strain) to characterize a conductance or resistance vessel, using a low-cost simple technique. The diameters (mean ± SEM) of the base and middle segments were 471 ± 4.97 and 540 ± 8.39 µm, respectively, the tail end was 253 ± 2.58 µm. To test reactivity, the whole tail arteries or segments were perfused under constant flow and the reactivity to phenylephrine (PHE; 0.01-300 µg) was evaluated before and after removal of the endothelium or drug administration. The maximal response (Emax) and sensitivity (pED50) to PHE of the whole tail and the base segment increased after endothelium removal or treatment with 100 µM L-NAME, which suggests modulation by nitric oxide. Indomethacin (10 µM) and tetraethylammonium (5 mM) did not change the Emax or pED50 of these segments. PHE and L-NAME increased the pED50 of the middle and the tail end only and indomethacin did not change pED50 or Emax. Tetraethylammonium increased the sensitivity only at the tail end, which suggests a blockade of vasodilator release. Results indicate that the proximal segment of the tail artery possesses a diameter compatible with a conductance vessel, while the tail end has the diameter of a resistance vessel. In addition, the vascular reactivity to PHE in the proximal segment is nitric oxide-dependent, while the tail end is dependent on endothelium-derived hyperpolarizing factor.

Time course of training-induced microcirculatory changes and of vegf expression in skeletal muscles of spontaneously hypertensive female rats

Exercise-induced vessel changes modulate arterial pressure (AP) in male spontaneously hypertensive rats (SHR). Vascular endothelial growth factor (VEGF) is important for angiogenesis of skeletal muscle. The present study evaluated the time course of VEGF and angiogenesis after short- and long-term exercise training of female SHR and Wistar Kyoto (WKY) rats, 8-9 weeks (200-250 g). Rats were allocated to daily training or remained sedentary for 3 days (N = 23) or 13 weeks (N = 23). After training, the carotid artery was catheterized for AP measurements. Locomotor (tibialis anterior and gracilis) and non-locomotor skeletal muscles (temporalis) were harvested and prepared for histologic and protein expression analyses. Training increased treadmill performance by all groups (SHR = 28%, WKY = 64%, 3 days) and (SHR = 141%, WKY = 122%, 13 weeks). SHR had higher values of AP than WKY (174 ± 4 vs 111 ± 2 mmHg) that were not altered by training. Three days of running increased VEGF expression (SHR = 28%, WKY = 36%) simultaneously with an increase in capillary-to-fiber ratio in gracilis muscle (SHR = 19%, WKY = 15%). In contrast, 13 weeks of training increased gracilis capillary-to-fiber ratio (SHR = 18%, WKY = 19%), without simultaneous changes in VEGF expression. Training did not change VEGF expression and capillarity of temporalis muscle. We conclude that training stimulates time- and tissue-dependent VEGF protein expression, independent of pressure levels. VEGF triggers angiogenesis in locomotor skeletal muscle shortly after the exercise starts, but is not involved in the maintenance of capillarity after long-term exercise in female rats.

Successful scale-up of human embryonic stem cell production in a stirred microcarrier culture system

Future clinical applications of human embryonic stem (hES) cells will require high-yield culture protocols. Currently, hES cells are mainly cultured in static tissue plates, which offer a limited surface and require repeated sub-culturing. Here we describe a stirred system with commercial dextran-based microcarriers coated with denatured collagen to scale-up hES cell production. Maintenance of pluripotency in the microcarrier-based stirred system was shown by immunocytochemical and flow cytometry analyses for pluripotency-associated markers. The formation of cavitated embryoid bodies expressing markers of endoderm, ectoderm and mesoderm was further evidence of maintenance of differentiation capability. Cell yield per volume of medium spent was more than 2-fold higher than in static plates, resulting in a significant decrease in cultivation costs. A total of 10(8) karyotypically stable hES cells were obtained from a unitary small vessel that needed virtually no manipulation during cell proliferation, decreasing risks of contamination. Spinner flasks are available up to working volumes in the range of several liters. If desired, samples from the homogenous suspension can be withdrawn to allow process validation needed in the last expansion steps prior to transplantation. Especially when thinking about clinical trials involving from dozens to hundreds of patients, the use of a small number of larger spinners instead of hundreds of plates or flasks will be beneficial. To our knowledge, this is the first description of successful scale-up of feeder- and Matrigel™-free production of undifferentiated hES cells under continuous agitation, which makes this system a promising alternative for both therapy and research needs.

Comparison of blood neoangiogenesis and lymphatic vascularization in colorectal adenomas from patients with and without concomitant colorectal cancer

Blood and lymphatic vessel proliferation is essential for tumor growth and progression. Most colorectal carcinomas develop from adenomas (adenoma-carcinoma sequence) in a process due to accumulation of molecular genetic alterations. About 5% of adenomatous polyps are expected to become malignant, but data on the differential angiogenic patterns of these lesions in patients with and without concomitant cancer are missing. The aim of the present study is to compare the angiogenic and lymphatic patterns of adenomatous polyps from patients with and without sporadic cancer. Thirty adenomatous polyps (15 from patients with another principal malignant lesion, and 15 from patients without cancer) were submitted to immunohistochemical staining for CD105 (marker for neoangiogenesis) and D2-40 (marker for lymphatic endothelium). Microvessel density and total vascular area were determined by computer image analysis to quantify the immunostained and total areas, and to assess the number of microvessels. Adenomas from patients with carcinoma showed significantly higher values of total vascular area determined by immunostaining for CD105 (cutoff value = 4386 µm²; P = 0.019) and of lymphatic microvessel density determined by immunostaining with D2-40 (cutoff value = 11.5; P = 0.041) when compared with those from patients without cancer. The present data indicate a significant increase in blood microvascular area and in lymphatic microvascular counts in adenomas removed from patients with cancer.

Can the fractal dimension be applied for the early diagnosis of non-proliferative diabetic retinopathy?

The fractal dimension has been employed as a useful parameter in the diagnosis of retinal disease. Avakian et al. (Curr Eye Res 2002; 24: 274-280), comparing the vascular pattern of normal patients with mild to moderate non-proliferative diabetic retinopathy (NPDR), found a significant difference between them only in the macular region. This significant difference in the box-counting fractal dimension of the macular region between normal and mild NPDR patients has been proposed as a method of precocious diagnosis of NPDR. The aim of the present study was to determine if fractal dimensions can really be used as a parameter for the early diagnosis of NPDR. Box-counting and information fractal dimensions were used to parameterize the vascular pattern of the human retina. The two methods were applied to the whole retina and to nine anatomical regions of the retina in 5 individuals with mild NPDR and in 28 diabetic but opthalmically normal individuals (controls), with age between 31 and 86 years. All images of retina were obtained from the Digital Retinal Images for Vessel Extraction (DRIVE) database. The results showed that the fractal dimension parameter was not sensitive enough to be of use for an early diagnosis of NPDR.

Oral rapamycin attenuates atherosclerosis without affecting the arterial responsiveness of resistance vessels in apolipoprotein E-deficient mice

The objective of the present study was to assess the effects of the immunosuppressant rapamycin (Rapamune®, Sirolimus) on both resistance vessel responsiveness and atherosclerosis in apolipoprotein E-deficient 8-week-old male mice fed a normal rodent diet. Norepinephrine (NE)-induced vasoconstriction, acetylcholine (ACh)- and sodium nitroprusside (SNP)-induced vasorelaxation of isolated mesenteric bed, and atherosclerotic lesions were evaluated. After 12 weeks of orally administered rapamycin (5 mg·kg-1·day-1, N = 9) and compared with untreated (control, N = 9) animals, rapamycin treatment did not modify either NE-induced vasoconstriction (maximal response: 114 ± 4 vs 124 ± 10 mmHg, respectively) or ACh- (maximal response: 51 ± 8 vs 53 ± 5%, respectively) and SNP-induced vasorelaxation (maximal response: 73 ± 6 vs 74 ± 6%, respectively) of the isolated vascular mesenteric bed. Despite increased total cholesterol in treated mice (982 ± 59 vs 722 ± 49 mg/dL, P < 0.01), lipid deposition on the aorta wall vessel was significantly less in rapamycin-treated animals (37 ± 12 vs 68 ± 8 µm² x 10³). These results indicate that orally administered rapamycin is effective in attenuating the progression of atherosclerotic plaque without affecting the responsiveness of resistance vessels, supporting the idea that this immunosuppressant agent might be of potential benefit against atherosclerosis in patients undergoing therapy.

Predictors of restenosis after percutaneous coronary intervention using bare-metal stents: a comparison between patients with and without dysglycemia

The objective of this study was to identify intravascular ultrasound (IVUS), angiographic and metabolic parameters related to restenosis in patients with dysglycemia. Seventy consecutive patients (77 lesions) selected according to inclusion and exclusion criteria were evaluated by the oral glucose tolerance test and the determination of insulinemia after a successful percutaneous coronary intervention (PCI) with a bare-metal stent. The degree of insulin resistance was calculated by the homeostasis model assessment of insulin resistance (HOMA-IR). Six-month IVUS and angiogram follow-up were performed. Thirty-nine patients (55.7%) had dysglycemia. The restenosis rate in the dysglycemic group was 37.2 vs 23.5% in the euglycemic group (P = 0.299). The predictors of restenosis using bivariate analysis were reference vessel diameter (RVD): £2.93 mm (RR = 0.54; 95%CI = 0.05-0.78; P = 0.048), stent area (SA): <8.91 mm² (RR = 0.66; 95%CI = 0.24-0.85; P = 0.006), stent volume (SV): <119.75 mm³ (RR = 0.74; 95%CI = 0.38-0.89; P = 0.0005), HOMA-IR: >2.063 (RR = 0.44; 95%CI = 0.14-0.64; P = 0.027), and fasting plasma glucose (FPG): ≤108.8 mg/dL (RR = 0.53; 95%CI = 0.13-0.75; P = 0.046). SV was an independent predictor of restenosis by multivariable analysis. Dysglycemia is a common clinical condition in patients submitted to PCI. The degree of insulin resistance, FPG, RVD, SA, and SV were correlated with restenosis. SV was inversely correlated with an independent predictor of restenosis in patients treated with a bare-metal stent.

Sildenafil prevents the increase of extravascular lung water and pulmonary hypertension after meconium aspiration in newborn piglets

Meconium aspiration syndrome causes respiratory failure after birth and in vivo monitoring of pulmonary edema is difficult. The objective of the present study was to assess hemodynamic changes and edema measured by transcardiopulmonary thermodilution in low weight newborn piglets. Additionally, the effect of early administration of sildenafil (2 mg/kg vo, 30 min after meconium aspiration) on this critical parameter was determined in the meconium aspiration syndrome model. Thirty-eight mechanically ventilated anesthetized male piglets (Sus scrofa domestica) aged 12 to 72 h (1660 ± 192 g) received diluted fresh human meconium in the airway in order to evoke pulmonary hypertension (PHT). Extravascular lung water was measured in vivo with a PiCCO monitor and ex vivo by the gravimetric method, resulting in an overestimate of 3.5 ± 2.3 mL compared to the first measurement. A significant PHT of 15 Torr above basal pressure was observed, similar to that of severely affected humans, leading to an increase in ventilatory support. The vascular permeability index increased 57%, suggesting altered alveolocapillary membrane permeability. Histology revealed tissue vessel congestion and nonspecific chemical pneumonitis. A group of animals received sildenafil, which prevented the development of PHT and lung edema, as evaluated by in vivo monitoring. In summary, the transcardiopulmonary thermodilution method is a reliable tool for monitoring critical newborn changes, offering the opportunity to experimentally explore putative therapeutics in vivo. Sildenafil could be employed to prevent PHT and edema if used in the first stages of development of the disease.

Effect of gender on training-induced vascular remodeling in SHR

There is accumulating evidence that physical inactivity, associated with the modern sedentary lifestyle, is a major determinant of hypertension. It represents the most important modifiable risk factor for cardiovascular diseases, which are the leading cause of morbidity and mortality for both men and women. In addition to involving sympathetic overactivity that alters hemodynamic parameters, hypertension is accompanied by several abnormalities in the skeletal muscle circulation including vessel rarefaction and increased arteriole wall-to-lumen ratio, which contribute to increased total peripheral resistance. Low-intensity aerobic training is a promising tool for the prevention, treatment and control of high blood pressure, but its efficacy may differ between men and women and between male and female animals. This review focuses on peripheral training-induced adaptations that contribute to a blood pressure-lowering effect, with special attention to differential responses in male and female spontaneously hypertensive rats (SHR). Heart, diaphragm and skeletal muscle arterioles (but not kidney arterioles) undergo eutrophic outward remodeling in trained male SHR, which contributed to a reduction of peripheral resistance and to a pressure fall. In contrast, trained female SHR showed no change in arteriole wall-to-lumen ratio and no pressure fall. On the other hand, training-induced adaptive changes in capillaries and venules (increased density) were similar in male and female SHR, supporting a similar hyperemic response to exercise.