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No description available.

Investigations into the safety of diagnostic ultrasound and mechanisms of therapeutic ultrasound have provided evidence of a number of cellular responses to ultrasound. These studies have mainly concentrated on cells in culture, while work on intact tissue employed mainly kHz ultrasound fields, although diagnostic and many therapeutic procedures are performed using MHz ultrasound. Vascular tissue is known to respond to a variety of physical and chemical signals, and so arteries were used as a model system in this thesis to study the effects of MHz ultrasound in vitro. Rings of equine carotid and lateral cecal mesenteric artery exhibited reversible, repeatable contraction on exposure to both pulsed and continuous wave 3.2 MHz ultrasound at acoustic powers up to 145 mW. Wall stress increased by up to 1.5% in carotid arteries and up to 2% in mesenteric arteries during exposure, and returned to basal levels after approximately 10 minutes. Contraction was endothelium independent, and was not affected by changes in the pulsing regime. The magnitude of contraction was dependent on the acoustic power, and the change in wall stress increased with increasing acoustic power in a linear fashion. The acoustic power dependence suggested the response was thermally mediated and this was confirmed by investigation of the response of arteries to non ultrasound generated heating, which also induced contraction. The effects of ultrasound and heating were also investigated in 1st order branches of the lateral cecal artery, as a model of a small artery. No response was observed in either case. In order to determine the cellular basis of the response of carotid and mesenteric arteries, the involvement of potassium ion channels in the response was investigated using a potassium channel blocker. The response of arteries to ultrasound was increased by inhibition of inward-rectifier potassium channels, which would otherwise help to return the cell membrane potential to the normal level. The change in wall stress was increased by 42% on average, confirming the involvement of these channels in the response. Contraction of arteries is mediated by an increase in intracellular calcium. The ion channel activity during non ultrasound generated heating was examined further by observation of intracellular calcium concentration using a fluorescent calcium sensitive dye. Increases in intracellular calcium were observed in carotid and large mesenteric arteries, which confirmed the thermal influence on ion channel function in these vessels. No such effect was observed in the smaller vessels.

During a single bout of aerobic exercise, blood flow is shunted to exercising tissues while blood flow is maintained or reduced to less metabolically active areas (i.e. splanchnic area and non-working muscles). Although increased sympathetic activation and multiple metabolic factors participate in redistributing blood flow during aerobic exercise, the precise mechanism is not entirely known. The renin-angiotensin system (RAS), specifically the local vascular wall RAS, has been hypothesized to participate in the redistribution of blood flow during exercise. This study aimed to investigate whether vascular wall RAS in the femoral arteries (an artery which feeds active tissues during exercise) was altered by acute exercise, and if these vascular RAS alterations led to specific changes in vasomotor function. Male Sprague Dawley rats were exercised on a motorized treadmill for 1h at 21m/min with 15% grade. Immediately following exercise femoral arteries were excised, cleaned of surrounding connective tissue, and vascular RAS was evaluated. There was a decrease in femoral ACE activity (~40%) and expression (~20%) following a single bout of exercise. No change was observed in AT1 and AT2 receptor expression. To evaluate the effect of acute exercise and vascular RAS on vessel reactivity, vasomotor properties of the femoral arteries were assessed via vasoconstrictor and vasodilatory dose-response curves. No changes were observed in femoral artery responses to potassium chloride (KCl), signifying that electromechanical coupling was not affected by exercise or RAS pharmacological interventions. However, a significant decrease in maximum phenylephrine (PE) constriction was observed for acutely exercise animals (~13%). Paired with the observed maintenance KCl-mediated constriction, it appears an acute bout of exercise is able to attenuate α-adrenergic receptor-mediated vasoconstriction in the femoral artery. The decrease in maximum α-adrenergic vasoconstriction may be attributed to vascular RAS. The decrease in ACE activity supports the production of local vasodilating factors. Blocking AT1 receptors with telmisartan decreased PE constriction in control and exercised animals. Combining AT1 and AT2 receptor blockade (with PD123319) eliminated the attenuating effect of telmisartan alone on PE constriction. This data suggests that the attenuating effect of AT1 receptor blockade, on PE constriction, may depend on AT2 receptor activation. In addition, combined AT1 receptor blockade and nitric oxide synthase inhibition eliminated both the lone AT1 receptor blockade effect and exercise effect on PE constriction. Together, this data suggests that reduced PE constriction following acute exercise, and AT1 receptor blockade, is dependent on nitric oxide production. Vasodilation to the nitric oxide donor sodium nitroprusside (SNP) was not altered following exercise or RAS pharmacological intervention, signifying no change in signaling downstream of NO production/release. Endothelium-dependent vasodilation to acetylcholine (ACh) was not affected by acute exercise. However, responses to ACh were modulated by RAS pharmacological interventions supporting the responses seen in PE constriction and signifying the participation of vascular RAS in vasomotor function.

During a single bout of aerobic exercise, blood flow is shunted to exercising tissues while blood flow is maintained or reduced to less metabolically active areas (i.e. splanchnic area and non-working muscles). Although increased sympathetic activation and multiple metabolic factors participate in redistributing blood flow during aerobic exercise, the precise mechanism is not entirely known. The renin-angiotensin system (RAS), specifically the local vascular wall RAS, has been hypothesized to participate in the redistribution of blood flow during exercise. This study aimed to investigate whether vascular wall RAS in the femoral arteries (an artery which feeds active tissues during exercise) was altered by acute exercise, and if these vascular RAS alterations led to specific changes in vasomotor function. Male Sprague Dawley rats were exercised on a motorized treadmill for 1h at 21m/min with 15% grade. Immediately following exercise femoral arteries were excised, cleaned of surrounding connective tissue, and vascular RAS was evaluated. There was a decrease in femoral ACE activity (~40%) and expression (~20%) following a single bout of exercise. No change was observed in AT1 and AT2 receptor expression. To evaluate the effect of acute exercise and vascular RAS on vessel reactivity, vasomotor properties of the femoral arteries were assessed via vasoconstrictor and vasodilatory dose-response curves. No changes were observed in femoral artery responses to potassium chloride (KCl), signifying that electromechanical coupling was not affected by exercise or RAS pharmacological interventions. However, a significant decrease in maximum phenylephrine (PE) constriction was observed for acutely exercise animals (~13%). Paired with the observed maintenance KCl-mediated constriction, it appears an acute bout of exercise is able to attenuate α-adrenergic receptor-mediated vasoconstriction in the femoral artery. The decrease in maximum α-adrenergic vasoconstriction may be attributed to vascular RAS. The decrease in ACE activity supports the production of local vasodilating factors. Blocking AT1 receptors with telmisartan decreased PE constriction in control and exercised animals. Combining AT1 and AT2 receptor blockade (with PD123319) eliminated the attenuating effect of telmisartan alone on PE constriction. This data suggests that the attenuating effect of AT1 receptor blockade, on PE constriction, may depend on AT2 receptor activation. In addition, combined AT1 receptor blockade and nitric oxide synthase inhibition eliminated both the lone AT1 receptor blockade effect and exercise effect on PE constriction. Together, this data suggests that reduced PE constriction following acute exercise, and AT1 receptor blockade, is dependent on nitric oxide production. Vasodilation to the nitric oxide donor sodium nitroprusside (SNP) was not altered following exercise or RAS pharmacological intervention, signifying no change in signaling downstream of NO production/release. Endothelium-dependent vasodilation to acetylcholine (ACh) was not affected by acute exercise. However, responses to ACh were modulated by RAS pharmacological interventions supporting the responses seen in PE constriction and signifying the participation of vascular RAS in vasomotor function.

In the pulmonary circulation, alveolar hypoxia contributes to blood flow regulation. Hypoxic pulmonary vasoconstriction (HPV) involves both pulmonary arteries and veins, but little is known of the contractile mechanisms specific to the veins. The aim of these studies was to examine the hypoxic response in small porcine intrapulmonary veins in relation to the arterial response, and investigate the effects of hypoxia on ion conductances in single myocytes from intrapulmonary veins. In wire myography experiments, intrapulmonary veins contracted more than sizematched arteries in response to hypoxia and agonists KCl and PGF2α. Venous contractions were inhibited by removal of extracellular Ca2+ or in the presence of Clchannel blocker NFA, effects not seen in the arteries. To examine the mechanisms of venous contraction at cellular level, single pulmonary vein smooth muscle cells (PVSMC) were freshly isolated and characterised morphologically and electrophysiologically for the first time. In patch-clamp studies, hypoxia reversibly inhibited a whole-cell outward current in the presence of BKCa channel antagonist Penitrem A. By subtracting currents recorded in normoxia and hypoxia, a novel hypoxia-sensitive K+ current (IK(H)) was revealed in PVSMC. IK(H) was a rapidly activating, partially inactivating current and was sensitive to KV channel blocker 4-AP. The biophysical properties of IK(H) revealed the voltage window of current availability with a peak near the resting membrane potential of PVSMC. In conclusion, these findings highlight differences between the contractile properties of veins and arteries and reveal a significant contribution of Ca2+ influx and an NFA-sensitive conductance during venous contraction to agonists and hypoxia. Furthermore, the results suggest that a novel hypoxia-sensitive KV current contributes to membrane potential under resting conditions in PVSMC and its inhibition by hypoxia may contribute to the initiation of HPV in porcine intrapulmonary veins.

A Acupuntura é um dos procedimentos na Medicina Tradicional Chinesa, cujos registros indicam seu surgimento há cerca de 4.500 anos. Esta técnica, mediante finas agulhas metálicas, inseridas em pontos específicos do corpo, pode compartilhar na recuperação da homeostasia. A teletermografia neste trabalho foi a técnica escolhida para demonstrar os eventuais efeitos térmicos da aplicação da acupuntura no ponto Taixi (R3), situado entre maléolo medial e o tendão do calcâneo, porque é uma técnica de alta sensibilidade que demonstra as alterações na circulação periférica da perna. Nove indivíduos saudáveis de ambos os sexos, escolhidos aleatoriamente, participaram deste estudo. A temperatura da sala onde o experimento foi conduzido não ultrapassou 21ºC. Inicialmente, estes indivíduos permaneceram por 10 minutos na sala para climatização quando foram captadas as primeiras imagens termográficas para padronização. Em seguida, foi introduzida uma agulha de acupuntura no ponto Taixi (R3) da perna direita até a obtenção do De Qi, com estimulação manual, a qual ali permaneceu por 15 minutos. Em seguida, foram captadas novas imagens teletermográficas. Foi observada redução significativa na temperatura da perna direita, em torno de 1,1ºC nos voluntários que receberam agulha de acupuntura no ponto Taixi (R3), com coeficiente de variação de p<0,0001, enquanto que na outra perna não estimulada a variação ocorreu em torno de 0,7ºC, com um coeficiente de variação não significativo de p>0,05. Este trabalho demonstrou que a acupuntura no ponto R3 promoveu alteração significativa na circulação periférica da perna, caracterizada por vasoconstrição, conseqüente do aumento do tônus simpático, demonstrada pela diminuição da temperatura em torno de 1,1ºC da área correspondente ao ponto estimulado. A teletermografia mostrou ser um método eficaz para avaliar os efeitos da acupuntura sobre a circulação periférica, confirmando resultados de estudos anteriores, embora em outras regiões do corpo do que aquela escolhida para este experimento. / Acupuncture is a procedure in Traditional Chinese Medicine, with registers that indicate it\'s appearance around 4.500 years ago. This technique, by means of fine metallic needles, inserted into specific points of the body, can help in the recuperation of homeostasis. The telethermography was chosen for this study as the means to demonstrate the eventual thermic effects of stimulating the acupuncture point Tai Xi (Kl 3) situated near to the medial malleolus on the posterior border of the tibia, because it is a highly sensitive technique that shows alterations in the peripheral circulation of the leg. Nine individuals of both sexes, chosen randomly, participated in this study. The temperature of the room where the experiment was carried out did not rise above 21ºC. At the start of the experiment the volunteer stayed exactly ten minutes in the room for acclimatization, then the first thermographic image was recorded for standardization purposes. Following this, an acupuncture needle was inserted into Tai Xi (KI 3) point only in the right leg, whose depth was limited to obtaining De Qi, only manual stimulation with fifteen minutes permanence in the site. After this period, new images were recorded. Significant reduction of all the right leg temperatures, by about 1.1ºC in all the volunteers that received the acupuncture needles in the Tai Xi (Kl 3) was noted, with a coefficient variation of p< 0.0001 that was statistically highly significant, while on the other non stimulated leg the variation that occurred was around 0.7ºC, with a non significant coefficient variation of p>0.05. The results of this study demonstrate that manual stimulation of the Tai Xi (Kl 3) acupuncture point, influences significantly peripheral vascular circulation, by means of sympathetic stimulation causing vasoconstriction. These results were visualized through telethermography and the thermic differences calculated were statistically significant characterized by vasoconstriction, as shown by the lowering of the temperature by 1.1ºC around the area correspondent to the stimulated point. The telethermography showed itself to be an efficient method for evaluation of the effects of acupuncture, confirming results of previous studies carried out with the same technology, albeit in other regions of the body than those chosen for this experiment.

A Acupuntura é um dos procedimentos na Medicina Tradicional Chinesa, cujos registros indicam seu surgimento há cerca de 4.500 anos. Esta técnica, mediante finas agulhas metálicas, inseridas em pontos específicos do corpo, pode compartilhar na recuperação da homeostasia. A teletermografia neste trabalho foi a técnica escolhida para demonstrar os eventuais efeitos térmicos da aplicação da acupuntura no ponto Taixi (R3), situado entre maléolo medial e o tendão do calcâneo, porque é uma técnica de alta sensibilidade que demonstra as alterações na circulação periférica da perna. Nove indivíduos saudáveis de ambos os sexos, escolhidos aleatoriamente, participaram deste estudo. A temperatura da sala onde o experimento foi conduzido não ultrapassou 21ºC. Inicialmente, estes indivíduos permaneceram por 10 minutos na sala para climatização quando foram captadas as primeiras imagens termográficas para padronização. Em seguida, foi introduzida uma agulha de acupuntura no ponto Taixi (R3) da perna direita até a obtenção do De Qi, com estimulação manual, a qual ali permaneceu por 15 minutos. Em seguida, foram captadas novas imagens teletermográficas. Foi observada redução significativa na temperatura da perna direita, em torno de 1,1ºC nos voluntários que receberam agulha de acupuntura no ponto Taixi (R3), com coeficiente de variação de p<0,0001, enquanto que na outra perna não estimulada a variação ocorreu em torno de 0,7ºC, com um coeficiente de variação não significativo de p>0,05. Este trabalho demonstrou que a acupuntura no ponto R3 promoveu alteração significativa na circulação periférica da perna, caracterizada por vasoconstrição, conseqüente do aumento do tônus simpático, demonstrada pela diminuição da temperatura em torno de 1,1ºC da área correspondente ao ponto estimulado. A teletermografia mostrou ser um método eficaz para avaliar os efeitos da acupuntura sobre a circulação periférica, confirmando resultados de estudos anteriores, embora em outras regiões do corpo do que aquela escolhida para este experimento. / Acupuncture is a procedure in Traditional Chinese Medicine, with registers that indicate it\'s appearance around 4.500 years ago. This technique, by means of fine metallic needles, inserted into specific points of the body, can help in the recuperation of homeostasis. The telethermography was chosen for this study as the means to demonstrate the eventual thermic effects of stimulating the acupuncture point Tai Xi (Kl 3) situated near to the medial malleolus on the posterior border of the tibia, because it is a highly sensitive technique that shows alterations in the peripheral circulation of the leg. Nine individuals of both sexes, chosen randomly, participated in this study. The temperature of the room where the experiment was carried out did not rise above 21ºC. At the start of the experiment the volunteer stayed exactly ten minutes in the room for acclimatization, then the first thermographic image was recorded for standardization purposes. Following this, an acupuncture needle was inserted into Tai Xi (KI 3) point only in the right leg, whose depth was limited to obtaining De Qi, only manual stimulation with fifteen minutes permanence in the site. After this period, new images were recorded. Significant reduction of all the right leg temperatures, by about 1.1ºC in all the volunteers that received the acupuncture needles in the Tai Xi (Kl 3) was noted, with a coefficient variation of p< 0.0001 that was statistically highly significant, while on the other non stimulated leg the variation that occurred was around 0.7ºC, with a non significant coefficient variation of p>0.05. The results of this study demonstrate that manual stimulation of the Tai Xi (Kl 3) acupuncture point, influences significantly peripheral vascular circulation, by means of sympathetic stimulation causing vasoconstriction. These results were visualized through telethermography and the thermic differences calculated were statistically significant characterized by vasoconstriction, as shown by the lowering of the temperature by 1.1ºC around the area correspondent to the stimulated point. The telethermography showed itself to be an efficient method for evaluation of the effects of acupuncture, confirming results of previous studies carried out with the same technology, albeit in other regions of the body than those chosen for this experiment.

Aging is associated with increases in regional and systemic vascular resistance and arterial blood pressure. One possible mechanism through which these age-associated alterations occur is enhanced vasoconstrictor responsiveness, or alterations in the structural properties of the resistance vasculature. We hypothesized that stiffness and vasoconstriction would be greater in skeletal muscle arterioles from old rats, and that endurance exercise training would ameliorate the associated with aging alterations. METHODS: Young sedentary (YS; 4 months), old sedentary (OS; 24 months), young trained (YT) and old trained (OT) male Fischer 344 rats were used. Training modality was treadmill exercise at 15 m/min up a 15o incline, 5 days/wk for 12wks. Skeletal muscle first-order arterioles were isolated for in vitro experimentation. Intraluminal diameter was measured in response to the cumulative addition of endothelin-1, norepinephrine, KCl, and isoproterenol. Stiffness was measure by examining the arterioles' stress and strain relation to increased luminal pressure in Ca++ free solution. RESULTS: Skeletal muscle arterioles had augmented vasoconstriction to endothelin-1 and norepinephrine. Adrenergic vasodilation was diminished in aged rat arterioles. Stiffness increased with age. Exercise training ameliorated the age-associated changes in stiffness and norepinephrine vasoconstriction. Exercise training did not alter endothelin-1 vasoconstriction or adrenergic vasodilation. CONCLUSIONS: These findings suggest that enhanced vascular sensitivity to vasoconstrictors and increased arteriole stiffness may play a role in the increase in skeletal muscle and systemic vascular resistance and, thus, contribute to the elevated blood pressure which occurs in aging humans. These results also demonstrate some of the cardioprotective effects of exercise training.