Intrauterine growth restriction increases circulating mitochondrial DNA and Toll-like receptor 9 expression in adult offspring: could aerobic training counteract these adaptations?

It has been demonstrated that intrauterine growth restriction (IUGR) can program increase cardiometabolic risk. There are also evidences of the correlation between IUGR with low-grade inflammation and, thus can contribute to development of several cardiometabolic comorbidities. Therefore, we investigated the influence of IUGR on circulating mitochondrial DNA (mtDNA)/Toll-like receptor 9 (TLR9) and TNF-α expression in adult offspring. Considering that the aerobic training has anti-inflammatory actions, we also investigated whether aerobic training would improve these inflammatory factors. Pregnant Wistar rats received ad libitum or 50% of ad libitum diet throughout gestation. At 8 weeks of age, male offspring from both groups were randomly assigned to control, trained control, restricted and trained restricted. Aerobic training protocol was performed on a treadmill and after that, we evaluated circulating mtDNA, cardiac protein expression of TLR9, plasma and cardiac TNF-α levels, and left ventricle (LV) mass. We found that IUGR promoted an increase in the circulating mtDNA, TLR9 expression and plasma TNF-α levels. Further, our results revealed that aerobic training can restore mtDNA/TLR9 content and plasma levels of TNF-α among restricted rats. The cardiac TNF-α content and LV mass were not influenced either by IUGR or aerobic training. In conclusion, IUGR can program mtDNA/TLR9 content, which may lead to high levels of TNF-α. However, aerobic training was able to normalize these alterations. These findings evidenced that the association of IUGR and aerobic training seems to exert an important interaction effect regarding pro-inflammatory condition and, aerobic training may be used as a strategy to reduce deleterious adaptations in IUGR offspring.

Intrauterine growth restriction-induced deleterious adaptations in endothelial progenitor cells: possible mechanism to impair endothelial function.

Intrauterine growth restriction (IUGR) can induce deleterious changes in the modulatory ability of the vascular endothelium, contributing to an increased risk of developing cardiovascular diseases in the long term. However, the mechanisms involved are not fully understood. Emerging evidence has suggested the potential role of endothelial progenitor cells (EPCs) in vascular health and repair. Therefore, we aimed to evaluate the effects of IUGR on vascular reactivity and EPCs derived from the peripheral blood (PB) and bone marrow (BM) in vitro. Pregnant Wistar rats were fed an ad libitum diet (control group) or 50% of the ad libitum diet (restricted group) throughout gestation. We determined vascular reactivity, nitric oxide (NO) concentration, and endothelial nitric oxide synthase (eNOS) protein expression by evaluating the thoracic aorta of adult male offspring from both groups (aged: 19-20 weeks). Moreover, the amount, functional capacity, and senescence of EPCs were assessed in vitro. Our results indicated that IUGR reduced vasodilation via acetylcholine in aorta rings, decreased NO levels, and increased eNOS phosphorylation at Thr495. The amount of EPCs was similar between both groups; however, IUGR decreased the functional capacity of EPCs from the PB and BM. Furthermore, the senescence process was accelerated in BM-derived EPCs from IUGR rats. In summary, our findings demonstrated the deleterious changes in EPCs from IUGR rats, such as reduced EPC function and accelerated senescence in vitro. These findings may contribute towards elucidating the possible mechanisms involved in endothelial dysfunction induced by fetal programming.

Baroreceptor reflex modulation by vasopressin microinjected into the nucleus tractus solitarii of conscious rats.

To determine whether the central vasopressinergic system at the level of nucleus tractus solitarii (NTS) modulates the reflex control of heart rate, we employed a new method for microinjection into the brainstem of conscious, freely moving rats. Baroreceptor reflex function was assessed during pressure changes induced by intravenous administration of phenylephrine (0.25-8 micrograms/kg) and sodium nitroprusside (0.5-16 micrograms/kg) in rats microinjected, through a permanent cannula into the brainstem, with saline, arginine vasopressin (AVP), or an AVP blocker. Baseline levels of pressure and heart rate were not changed by either peptide pretreatment. Restricted injection of AVP (20 ng-0.2 microliter) into the NTS attenuated the reflex bradycardia during pressure increases, with an upward displacement of the baroreceptor reflex function line (p less than 0.01) without change in the sensitivity. Local blockade of endogenous AVP, d(CH2)5Tyr(Me)AVP (1 microgram-0.2 microliter), depressed baroreceptor reflex sensitivity with intense bradycardia to either small or large pressure increases. Baroreceptor reflex control of heart rate in response to decreases in pressure was preserved during pretreatment with AVP, whereas endogenous blockade of AVP increased baroreceptor reflex sensitivity. These effects were specific to the NTS, since in another four rats there were no effects when the injections were made 1 mm above, into the cerebellum. The changes in baroreceptor reflex control of heart rate in conscious, unrestrained rats caused by administration of AVP and its endogenous blockade provide evidence that central vasopressinergic synapses at the NTS are important physiological modulators of baroreceptor reflex function.

Angiotensin II as a modulator of baroreceptor reflexes in the brainstem of conscious rats.

The effect of microinjection into the nucleus tractus solitarii (NTS) of angiotensin II (Ang II) on baroreceptor control of heart rate (HR) in conscious, freely moving rats was evaluated with a new method of long-term cannulation of the dorsal brainstem areas. Reflex changes in HR were produced by intravenous bolus injections of either phenylephrine or sodium nitroprusside (0.2-25.6 micrograms/kg) both after saline and after unilateral microinjection of Ang II into the NTS (24 ng, 0.2 microliter) and compared with those produced after administration of Ang II into the fourth ventricle (24 ng, 0.2 microliter) or intravenously (1-2 ng/kg/min). Baseline levels of mean arterial pressure (MAP) and HR were not affected by the route of Ang II application but reflex bradycardia during MAP increase was significantly attenuated after injections of Ang II into the NTS. Both the slope and the intercept of the regression line function between delta HR and delta MAP were reduced by 43% from the control value of -1.55 +/- 0.13 beats/min/mm Hg (p less than 0.01) and -14 +/- 5 beats/min (p less than 0.05), respectively. Similar reductions were observed after Ang II administration into the fourth ventricle or intravenously, although microinjections into the cerebellum produced no effect. Endogenous blockade of Ang II by saralasin (22 ng) in the NTS facilitated the bradycardic response (-2.29 +/- 0.91 beats/min/mm Hg). Nitroprusside-induced tachycardia was not altered by Saralasin microinjection into the NTS or by Ang II application to the NTS, fourth ventricle, or intravenously.(ABSTRACT TRUNCATED AT 250 WORDS)

Baroreceptor reflex control of heart rate during development of coarctation hypertension.

To study whether resetting of the baroreceptors is accompanied by normal reflex activity to the heart, we analyzed time-course changes of pressure, heart rate, baroreceptor reflex sensitivity, and plasma renin activity during the development of coarctation hypertension. Baseline heart rate was measured daily, and plasma renin activity and reflex changes in heart rate (bolus injections of either phenylephrine or nitroprusside, 0.2-25.6 micrograms/kg i.v.) were recorded at different times in coarcted and sham-coarcted rats. Hypertension was stable (approximately 39% from baseline mean arterial pressure of 112 +/- 3 mm Hg), whereas heart rate (333 +/- 4 beats per minute) showed a biphasic behavior: bradycardia at 6 hours (264 +/- 7 beats per minute) and tachycardia at 5 days (418 +/- 14 beats per minute). On day 10 of hypertension, heart rate was normal. Plasma renin activity was markedly increased only after 6 hours (4.9 times). Reflex bradycardia exhibited a progressive impairment: The slopes of the regression lines between changes in heart rate and changes in mean arterial pressure were not significantly reduced at 6 and 48 hours when the resetting was in development (changes of 17% and 28% from a control of -1.89 +/- 0.20 beats per minute/mm Hg) but were significantly depressed after the resetting had been completed (-51% and -56% at 5 and 10 days, respectively). Reflex tachycardia was significantly reduced in all periods studied (75%, 78%, 52%, and 61% at 6 hours and 2, 5, and 10 days, respectively; -3.92 +/- 0.42 beats per minute/mm Hg in sham rats).(ABSTRACT TRUNCATED AT 250 WORDS)

Arginine vasopressin modulates the central action of angiotensin II in the dog.

Endogenous vasopressin may interact with central autonomic nervous system factors in the regulation of cardiovascular function. In 25 morphine/chloralose-anesthetized dogs, we studied the magnitude of the pressor response produced by an infusion of angiotensin II (AII) into the vertebral arteries (VA), before and after intracisternal (n = 10), intravertebral (n = 9), or intravenous (n = 6) administration of a competitive antagonist of arginine vasopressin (AVP) [d(CH2)5Tyr(Me) AVP]. The dose response curve to vertebral artery infusion of AII (range 2-20 ng/kg/min) was significantly (p less than 0.05) shifted to the right of control after injection of the AVP antagonist (10 micrograms/kg) into the cisterna magna; the ED at 20 mm Hg being almost double after central AVP blockade. This effect of AVP blockade was confined only to the cardiovascular response mediated by AII via the vertebral arteries. When pressor doses of AII were injected into either a vein (i.v.) or the cisterna magna of these same dogs, the increases in mean blood pressure were the same before and after AVP antagonist treatment. In another group of anesthetized dogs, we investigated whether the reduced reactivity to intravertebral AII could be duplicated by giving the AVP antagonist either via the vertebral artery or i.v. Only the cisterna magna route was effective in causing a blunting of the pressor response to vertebral artery AII. These data demonstrate a previously unknown interaction between vasopressin and the centrally mediated pressor response to intravertebral AII.

Chronic AT1 receptor blockade alters aortic nerve activity in hypertension.

In the chronic phase of coarctation hypertension (CH) we have shown both reduction in baroreceptor sensitivity (Hypertension. 1992;19[suppl II]:II-198-II-201.) and normalization of the depressed baroreceptor reflex control of heart rate, even with the persistence of hypertension in losartan-treated animals (Am J Physiol. 1995;269:H812-H818). In the present study we analyzed the effects of angiotensin II blockade on afferent aortic nerve activity of CH and sham-operated groups treated chronically with vehicle or losartan (10 mg/kg per day p.o.). CH was induced by subdiaphragmatic aortic coarctation, and the treatments lasted 8 days (4 control and 4 experimental days). Aortic pressure (conscious rats) and aortic nerve activity simultaneous to pressure (anesthetized rats) were recorded on the fourth day of the experimental period. Losartan-treated rats showed reduced tail pressure (104+/-3 versus 117+/-3 mm Hg in the vehicle group). In both groups, aortic coarctation caused a significant increase in pressure (25% and 28%, respectively) and a depression of the aortic nerve activity/pressure relationship when compared with sham-operated coarcted animals. In the physiological range of pressure changes, the depression was significantly smaller after losartan treatment (3.30+/-0.33 versus 2.18+/-0.37%/mm Hg in the losartan- and vehicle-treated CH groups, respectively, versus 5.05+/-0.33%/mm Hg in the sham-operated vehicle-treated group). Angiotensin type 1 (AT1) receptor blockade was also accompanied by reduced variability of the afferent discharge. The data suggested that apart from its pressure effect, angiotensin II acts at AT1 receptors to decrease the sensitivity of aortic afferents during physiological (+/-10 mm Hg) increases and decreases in pressure. Thus, angiotensin II may contribute to reductions of baroreceptor gain in chronic hypertension.

Role of endogenous nitric oxide in the nucleus tratus solitarii on baroreflex control of heart rate in spontaneously hypertensive rats.

OBJECTIVE: Toinvestigate the modulatory effect of endogenous nitric oxide (NO) in the nucleus tractus solitarii (NTS) on the baroreceptor reflex control of heart rate in conscious spontaneously hypertensive (SHR) and normotensive (WKY) rats. DESIGN AND METHODS: Male age- and weight-matched SHR and WKY chronically instrumented with cannulas in the NTS, artery and vein were used. Basal pressure (AP), heart rate (HR) and reflex HR responses during loading/unloading of baroreceptors (phenylephrine/sodium nitroprusside, iv) were recorded during vehicle (3 nl/min) NG-monomethyl-L-arginine (L-NMMA) and L-arginine (L-Arg) infusions into the NTS. Constitutive NO synthase (NOS) activity was inferred by 3H-citrulline formation in the dorsal brain stem of other SHR and WKY groups. RESULTS: In SHR a small dose of L-NMMA (30 ng/kg/min) restricted to the NTS did not change AP and HR (185+/-4 mmHg, 373+/-12 beats/min, respectively), but decreased the HR range (57+/-7 beats/min, a 34% reduction, P< 0.05) without changing further the impaired gain of baroreceptor reflex control of HR. In the WKY group similar results (significant 32% reduction in HR range, gain unchanged) were only attained with a dose 10 times higher (L-NMMA(NTS) = 300 ng/kg/min), no effect being observed with the small dose (HR range = 163+/-12 beats/min). In SHR, L-Arg(NTS) (900 ng/kg/min) did not improve baroreflex control of HR, but restored the depression of HR range when given after L-NMMA(NTS). Basal NOS activity in the dorsal brain stem was reduced in SHR (P < 0.05) when compared to WKY group. CONCLUSIONS: NO modulates, at the NTS level, the baroreceptor reflex control of HR in both SHR and WKY not by altering the gain, but by increasing HR range during afferent stimulation. In SHR the depressed NO modulation is in accordance with the smaller NOS activity in the dorsal brain stem.

Exercise training normalizes wall-to-lumen ratio of the gracilis muscle arterioles and reduces pressure in spontaneously hypertensive rats.

OBJECTIVE: To investigate mechanisms underlying the training-induced blood pressure-lowering effect we analyzed the hemodynamic responses and morphometric changes of the skeletal muscle microcirculation of spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats during an exercise training program. DESIGN TRAINING: (50-60% VO2 max) was performed on a treadmill for 13 weeks and control groups were kept sedentary over the same period of time. Trained and sedentary rats were chronically instrumented for hindlimb flow and arterial pressure (AP) recordings under conscious unrestrained conditions. Gracilis and myocardial muscle samples were obtained for morphometric analysis after transcardiac perfusion of fixative. RESULTS: SHR, when compared to WKY presented an elevated blood pressure, an increased relative hindlimb vascular resistance, capillary rarefaction in both gracilis and myocardium and an increased wall-to-lumen ratio of gracilis arterioles. Training increased significantly both capillary density and capillary/fiber ratio in the gracilis and myocardium of WKY and SHR groups, causing a complete reversal of capillary rarefaction in trained SHR. In SHR, training also reduced resting blood pressure and caused normalization of both relative hindlimb vascular resistance and gracilis arterioles wall-to-lumen ratio. Regression analysis revealed strong positive correlation between hindlimb vascular resistance and mean AP (MAP) and between arterioles wall-to-lumen ratio and MAP. CONCLUSIONS: The results suggest that low-intensity training can significantly reduce pressure in SHR while normalizing both the arteriole morphology and the resistance of the skeletal muscle microcirculation.

Exercise training causes skeletal muscle venular growth and alters hemodynamic responses in spontaneously hypertensive rats.

OBJECTIVE: To investigate whether training changes skeletal muscle venular profile and hemodynamic responses to exercise we studied spontanesouly hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats submitted to training programme (T = 50-60% of VO2max). DESIGN: Training (T) was performed on a treadmill over a period of 13 weeks. Age-matched control groups were kept sedentary (S). T and S rats were chronically instrumented for hindlimb flow (HLF) and arterial pressure (AP) measurements at rest, during dynamic exercise and recovery in two different situations: control and after extensive intravenous blockade (hexamethonium + losartan + Nomega-nitro-L-arginine methyl ester + hydralazine). For morphometric analysis, skeletal muscle samples (gracilis) were obtained after transcardiac perfusion with fixative. RESULTS: T caused a significant reduction of resting mean arterial pressure (MAP) (-11%) only in the SHR group without changing basal HLF. In the sedentary SHR (SHRs), basal relative hindlimb resistance was increased by 45%, but was significantly reduced after T (P < 0.05). During dynamic exercise, MAP increased similarly (10-20 mmHg) in all groups. HLF increases were similar for the four groups up to 0.8 km/h; at higher workloads, HLF was higher in trained SHR (SHRT) versus trained WKY (WKYT) (3.9- versus 2.9-fold increase over basal HLF, respectively). After blockade (and pressure correction with IV phenylephrine infusion), steady-state exercise was performed with similar hindlimb vasodilation in all groups and was accompanied by MAP reduction (-17 +/- 8 mmHg) only in SHRT group. Skeletal muscle venular profile (density, diameter and lumen cross-sectional area) was similar in WKY(T), WKY(S) and SHR(S), but significantly increased in SHR(T). In this group the two-fold increase in venule density was correlated with both the reduction in baseline MAP and the increase in HLF during dynamic exercise. CONCLUSIONS: The results suggest that increased venule density is a specific adaptation of SHR skeletal muscle to training. Venular growth may contribute to both the pressure-lowering effect and the large HLF at high exercise intensities observed in the trained SHR.

Oxytocin in the NTS. A new modulator of cardiovascular control during exercise.

The role of brain stem oxytocinergic projections in the modulation of heart rate control during exercise is discussed on the basis of both changes in endogenous peptide content and heart rate changes observed during exercise. Running on a treadmill caused an increase in oxytocin content in dorsal/ventral brain stem areas and spinal cord, specifically in trained rats. Trained rats pretreated with a specific oxytocin receptor antagonist into the dorsal brain stem area (corresponding to the nucleus tractus solitarii and dorsal motor nucleus of the vagus, or NTS/DMV) showed a significant potentiation of exercise tachycardia with no change in the blood pressure response. The same treatment in sedentary rats was without effect. On the other hand, administration of exogenous oxytocin into this area caused significant blunting of exercise tachycardia in both groups, with no change in the pressure response. It is proposed that long-descending oxytocinergic pathways from the hypothalamus to the NTS/DMV area serve as a link between the two main neural controllers of the circulation--that is, the central command and feedback control mechanisms driven by the peripheral receptor signals. Our results strongly suggest that oxytocinergic input to NTS/DMV, by restraining the tachycardic response of trained individuals, contributes to the smaller response observed after training, without compromising cardiac output adjustment and the circulatory demand during exercise.

Endogenous vasopressin modulates the cardiovascular responses to exercise.

The role of brain-stem vasopressinergic projections in the genesis of reflex bradycardia and in the modulation of heart rate control during exercise is discussed on the basis of both changes in endogenous peptide content and heart rate changes observed during exercise. Dynamic running caused an increase in vasopressin content specifically in dorsal and ventral brain-stem areas. Rats pretreated with vasopressin or the V1 receptor antagonist into the nucleus tractus solitarii (NTS) showed a significant potentiation or a marked blunting of the exercise tachycardia, respectively, without any change in the blood pressure response. It is proposed that long-descending vasopressinergic pathways from the hypothalamus to the NTS serves as one link between the two main neural controllers of the circulation, that is, the central command and feedback control mechanisms driven by the peripheral receptors signals. Therefore vasopressinergic input contributes to the adjustment of heart rate response (and cardiac output) to the circulatory demand during exercise.

Receptor changes in the nucleus tractus solitarii of the rat after exercise training.

PURPOSE: The aim of the present study was to evaluate neurotransmitter receptor changes in the nucleus tractus solitarii (NTS) of the rat after exercise training. METHODS: Twelve Wistar Kyoto rats were used. Six rats were submitted to a progressive training program in which they ran on a treadmill 5 d x wk(-1) for 13 wk (trained). The other rats were kept as controls (sedentary). After this period, the rats were killed and the brains processed for quantitative receptor autoradiography. Coronal brain sections were obtained using a cryostat and were incubated with a specific buffer solution containing [(3)H]vasopressin or (3)Hp-aminoclonidine. RESULTS: In the NTS of the trained rats, a decrease in the values of binding parameters (IC(50) and K(D)) of vasopressin receptors was observed, indicating an increase in the affinity of vasopressin receptors. On the other hand, a decreased affinity was observed for alpha(2)-adrenoceptors in the NTS of the trained rats in comparison with the sedentary animals. CONCLUSION: Exercise training leads to changes in vasopressin and alpha(2)-adrenoceptors, which may explain several physiological alterations occurring during physical activity.

Vasopressin in the nucleus tractus solitarius: a modulator of baroreceptor reflex control of heart rate.

1. The main role of the nucleus tractus solitarius (NTS) as a relay center for viscerosensory fibers from the periphery and for pathways from modulatory autonomic centers is reviewed on the basis of its anatomical connections and neurotransmitter content. 2. Vasopressin is present in the entire neuroaxis and is of great importance in the control of cardiovascular function. The high endogenous content and receptor density, and the unique organization of vasopressin fibers projecting to the NTS are fundamental features for the modulatory effect exerted by vasopressin at the NTS on the baroreceptor reflex control of heart rate. 3. Vasopressinergic pathways from the paraventricular nucleus of the hypothalamus to the NTS constitute a physiological mechanism for the tonic maintenance of the baroreflex sensitivity and for displacing the heart rate response to higher values during increased activity, without changing the baroreflex sensitivity. This type of mechanism should play an important role in facilitating the tachycardic response during isotonic exercise.

Endogenous vasopressin and the central control of heart rate during dynamic exercise.

The present article contains a brief review on the role of vasopressinergic projections to the nucleus tractus solitarii in the genesis of reflex bradycardia and in the modulation of heart rate control during exercise. The effects of vasopressin on exercise tachycardia are discussed on the basis of both the endogenous peptide content changes and the heart rate response changes observed during running in sedentary and trained rats. Dynamic exercise caused a specific vasopressin content increase in dorsal and ventral brainstem areas. In accordance, rats pretreated with the peptide or the V1 blocker into the nucleus tractus solitarii showed a significant potentiation or a marked blunting of the exercise tachycardia, respectively, without any change in the pressure response to exercise. It is proposed that the long-descending vasopressinergic pathway to the nucleus tractus solitarii serves as one link between the two main neural controllers of circulation, i.e., the central command and feedback control mechanisms driven by the peripheral receptors. Therefore, vasopressinergic input could contribute to the adjustment of heart rate response (and cardiac output) to the circulatory demand during exercise.

Validation of transit-time flowmetry for chronic measurements of regional blood flow in resting and exercising rats.

The objective of the present study was to validate the transit-time technique for long-term measurements of iliac and renal blood flow in rats. Flow measured with ultrasonic probes was confirmed ex vivo using excised arteries perfused at varying flow rates. An implanted 1-mm probe reproduced with accuracy different patterns of flow relative to pressure in freely moving rats and accurately quantitated the resting iliac flow value (on average 10.43 +/- 0.99 ml/min or 2.78 +/- 0.3 ml min-1 100 g body weight-1). The measurements were stable over an experimental period of one week but were affected by probe size (resting flows were underestimated by 57% with a 2-mm probe when compared with a 1-mm probe) and by anesthesia (in the same rats, iliac flow was reduced by 50-60% when compared to the conscious state). Instantaneous changes of iliac and renal flow during exercise and recovery were accurately measured by the transit-time technique. Iliac flow increased instantaneously at the beginning of mild exercise (from 12.03 +/- 1.06 to 25.55 +/- 3.89 ml/min at 15 s) and showed a smaller increase when exercise intensity increased further, reaching a plateau of 38.43 +/- 1.92 ml/min at the 4th min of moderate exercise intensity. In contrast, exercise-induced reduction of renal flow was smaller and slower, with 18% and 25% decreases at mild and moderate exercise intensities. Our data indicate that transit-time flowmetry is a reliable method for long-term and continuous measurements of regional blood flow at rest and can be used to quantitate the dynamic flow changes that characterize exercise and recovery.

Importance of the time course of aortic diastolic calibre dilation for baroreceptor resetting in acute hypertension.

By means of a chronically implanted electrolytic transducer, changes in the aortic calibre were studied in conscious rats during the onset of acute hypertension produced by subdiaphragmatic aortic constriction. The rise of pressure to its maximum (153 +/- 5 versus 101 +/- 4 mmHg during the control period) was immediate after aortic constriction and hypertension remained stable during the entire period of observation. An equivalent (50 mmHg) but transient increase in pressure produced an increase of 0.8% in mean aortic calibre, whereas after 6 h of hypertension, dilation was 1.2%, the distensibility remaining unchanged. However, in both circumstances the displacement of the diastolic calibre was greater (80%) than the increase in pulsation (20%). After 48 h of hypertension, distensibility increased, allowing the aorta to achieve maximal dilation (6.8%) and maximal pulsation. Therefore the time taken (48 h) for the aorta to achieve a new state of resting diastolic equilibrium in acute hypertension coincides with the time course for complete resetting of the aortic baroreceptors, demonstrated before in the same preparation.

Structural and functional alterations induced by two sulfonamide antibiotics on barley plants.

Synthetic veterinary medicines are introduced routinely in the environment after animal treatment to prevent and control infectious diseases and up to 80% the administered dose can be excreted unaltered. As a consequence, the soil is the environment most contaminated by such molecules. However, information about their implications on the growth of vegetal organisms is still scarce. With the aim of better elucidating the effects of veterinary antibiotics on plants, barley was grown in a nutrient solution containing 40 µM (about 11,500 µg L(-1)) of two well-known sulfonamide antibiotics, sulfadimethoxine (SDM) and sulfamethazine (SZ). After 15 d of treatment, the effects on root apparatus were particularly evident, while the photosynthetic tissues remained almost unaffected. SDM and SZ stimulated root hairs and lateral root development a few mm behind the root tips. In particular, from a structural point of view, treated plants showed root shortening and an advanced differentiation in comparison to controls, later confirmed using light microscopy. At a functional level, the two active molecules were found to induce root electrolyte release, such as K(+), possibly due to an impairment of membrane permeability. The research concludes that sulfonamides can have profound effects on morphology and functionality of roots of crop plants. As these alterations might have consequences on their productivity, further studies are necessary to assess effects on plants at laboratory and field conditions.

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.