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Coral L Murrant - One of the best experts on this subject based on the ideXlab platform.

  • capillary response to skeletal muscle contraction evidence that redundancy between Vasodilators is physiologically relevant during active hyperaemia
    The Journal of Physiology, 2018
    Co-Authors: Iain R Lamb, Nicole M Novielli, Coral L Murrant
    Abstract:

    KEY POINTS:The current theory behind matching blood flow to metabolic demand of skeletal muscle suggests redundant interactions between metabolic Vasodilators. Capillaries play an important role in blood flow control given their ability to respond to muscle contraction by causing conducted vasodilatation in upstream arterioles that control their perfusion. We sought to determine whether redundancies occur between Vasodilators at the level of the capillary by stimulating the capillaries with muscle contraction and Vasodilators relevant to muscle contraction. We identified redundancies between potassium and both adenosine and nitric oxide, between nitric oxide and potassium, and between adenosine and both potassium and nitric oxide. During muscle contraction, we demonstrate redundancies between potassium and nitric oxide as well as between potassium and adenosine. Our data show that redundancy is physiologically relevant and involved in the coordination of the vasodilator response during muscle contraction at the level of the capillaries. ABSTRACT:We sought to determine if redundancy between Vasodilators is physiologically relevant during active hyperaemia. As inhibitory interactions between Vasodilators are indicative of redundancy, we tested whether Vasodilators implicated in mediating active hyperaemia (potassium (K+ ), adenosine (ADO) and nitric oxide (NO)) inhibit one another's vasodilatory effects through direct application of pharmacological agents and during muscle contraction. Using the hamster cremaster muscle and intravital microscopy, we locally stimulated capillaries with one vasodilator in the absence and the presence of a second vasodilator (10-7 m S-nitroso-N-acetylpenicillamine (SNAP), 10-7 m ADO, 10 mm KCl) applied sequentially and simultaneously, and observed the response in the associated upstream 4A arteriole controlling the perfusion of the stimulated capillary. We found that KCl significantly attenuated SNAP- and ADO-induced vasodilatations by ∼49.7% and ∼128.0% respectively and ADO significantly attenuated KCl- and SNAP-induced vasodilatations by ∼94.7% and ∼59.6%, respectively. NO significantly attenuated KCl vasodilatation by 93.8%. Further, during muscle contraction we found that inhibition of NO production using l-NG -nitroarginine methyl ester and inhibition of ADO receptors using xanthine amine congener was effective at inhibiting contraction-induced vasodilatation but only in the presence of K+ release channel inhibition. Thus, only when the inhibiting vasodilator K+ was blocked was the second vasodilator, NO or ADO, able to produce effective vasodilatation. Therefore, we show that there are inhibitory interactions between specific Vasodilators at the level of the capillary. Further, these inhibitions can be observed during muscle contraction indicating that redundancies between Vasodilators are physiologically relevant and influence vasodilatation during active hyperaemia.

  • potassium inhibits nitric oxide and adenosine arteriolar vasodilatation via kir and na k atpase implications for redundancy in active hyperaemia
    The Journal of Physiology, 2015
    Co-Authors: Iain R Lamb, Coral L Murrant
    Abstract:

    Key points Multiple Vasodilators have been identified as being important in matching blood flow to the metabolism of contracting skeletal muscle and it has been hypothesized that this process is governed by redundancy between Vasodilators, where one vasodilator can compensate for the loss of another. In the present study, we aimed to determine whether redundancy between Vasodilators exists by investigating whether Vasodilators relevant to skeletal muscle contraction can inhibit the effects of other Vasodilators. We show that potassium can inhibit vasodilatations induced by adenosine and nitric oxide, and also that adenosine and nitric oxide can interact in a way that changes over time. Furthermore, we show that inward rectifying potassium channels and Na+/K+ATPase are partially mechanistically responsible for the interaction between potassium and adenosine and nitric oxide. Our data provide proof of principle that Vasodilators relevant to muscle contraction interact and also that redundancy may govern the processes of active hyperaemia. Abstract Redundancy, in active hyperaemia, where one vasodilator can compensate for another if the first is missing, would require that one vasodilator inhibits the effects of another; therefore, if the first vasodilator is inhibited, its inhibitory influence on the second vasodilator is removed and the second vasodilator exerts a greater vasodilatory effect. We aimed to determine whether Vasodilators relevant to skeletal muscle contraction [potassium chloride (KCl), adenosine (ADO) and nitric oxide] inhibit one another and, in addition, to investigate the mechanisms for this interaction. We used the hamster cremaster muscle and intravital microscopy to directly visualize 2A arterioles when exposed to a range of concentrations of one vasodilator [10−8 to 10−5 m S-nitroso-N-acetyl penicillamine (SNAP), 10−8 to 10−5 m ADO, 10 and 20 mm KCl] in the absence and then in the presence of a second vasodilator (10−7 m ADO, 10−7 m SNAP, 10 mm KCl). We found that KCl significantly attenuated SNAP-induced vasodilatations by ∼65.8% and vasodilatations induced by 10−8 to 10−6 m ADO by ∼72.8%. Furthermore, we observed that inhibition of KCl vasodilatation, by antagonizing either Na+/K+ ATPase using ouabain or inward rectifying potassium channels using barium chloride, could restore the SNAP-induced vasodilatation by up to ∼53.9% and 30.6%, respectively, and also restore the ADO-induced vasodilatations by up to ∼107% and 76.7%, respectively. Our data show that Vasodilators relevant to muscle contraction can interact in a way that alters the effectiveness of other Vasodilators. These data suggest that active hyperaemia may be the result of complex interactions between multiple Vasodilators via a redundant control paradigm.

  • potassium inhibits nitric oxide and adenosine arteriolar vasodilatation via kir and na k atpase implications for redundancy in active hyperaemia
    The Journal of Physiology, 2015
    Co-Authors: Iain R Lamb, Coral L Murrant
    Abstract:

    Redundancy, in active hyperaemia, where one vasodilator can compensate for another if the first is missing, would require that one vasodilator inhibits the effects of another; therefore, if the first vasodilator is inhibited, its inhibitory influence on the second vasodilator is removed and the second vasodilator exerts a greater vasodilatory effect. We aimed to determine whether Vasodilators relevant to skeletal muscle contraction [potassium chloride (KCl), adenosine (ADO) and nitric oxide] inhibit one another and, in addition, to investigate the mechanisms for this interaction. We used the hamster cremaster muscle and intravital microscopy to directly visualize 2A arterioles when exposed to a range of concentrations of one vasodilator [10(-8) to 10(-5) M S-nitroso-N-acetyl penicillamine (SNAP), 10(-8) to 10(-5) M ADO, 10 and 20 mM KCl] in the absence and then in the presence of a second vasodilator (10(-7) M ADO, 10(-7) M SNAP, 10 mM KCl). We found that KCl significantly attenuated SNAP-induced vasodilatations by ∼65.8% and vasodilatations induced by 10(-8) to 10(-6) M ADO by ∼72.8%. Furthermore, we observed that inhibition of KCl vasodilatation, by antagonizing either Na(+)/K(+) ATPase using ouabain or inward rectifying potassium channels using barium chloride, could restore the SNAP-induced vasodilatation by up to ∼53.9% and 30.6%, respectively, and also restore the ADO-induced vasodilatations by up to ∼107% and 76.7%, respectively. Our data show that Vasodilators relevant to muscle contraction can interact in a way that alters the effectiveness of other Vasodilators. These data suggest that active hyperaemia may be the result of complex interactions between multiple Vasodilators via a redundant control paradigm.

Iain R Lamb - One of the best experts on this subject based on the ideXlab platform.

  • capillary response to skeletal muscle contraction evidence that redundancy between Vasodilators is physiologically relevant during active hyperaemia
    The Journal of Physiology, 2018
    Co-Authors: Iain R Lamb, Nicole M Novielli, Coral L Murrant
    Abstract:

    KEY POINTS:The current theory behind matching blood flow to metabolic demand of skeletal muscle suggests redundant interactions between metabolic Vasodilators. Capillaries play an important role in blood flow control given their ability to respond to muscle contraction by causing conducted vasodilatation in upstream arterioles that control their perfusion. We sought to determine whether redundancies occur between Vasodilators at the level of the capillary by stimulating the capillaries with muscle contraction and Vasodilators relevant to muscle contraction. We identified redundancies between potassium and both adenosine and nitric oxide, between nitric oxide and potassium, and between adenosine and both potassium and nitric oxide. During muscle contraction, we demonstrate redundancies between potassium and nitric oxide as well as between potassium and adenosine. Our data show that redundancy is physiologically relevant and involved in the coordination of the vasodilator response during muscle contraction at the level of the capillaries. ABSTRACT:We sought to determine if redundancy between Vasodilators is physiologically relevant during active hyperaemia. As inhibitory interactions between Vasodilators are indicative of redundancy, we tested whether Vasodilators implicated in mediating active hyperaemia (potassium (K+ ), adenosine (ADO) and nitric oxide (NO)) inhibit one another's vasodilatory effects through direct application of pharmacological agents and during muscle contraction. Using the hamster cremaster muscle and intravital microscopy, we locally stimulated capillaries with one vasodilator in the absence and the presence of a second vasodilator (10-7 m S-nitroso-N-acetylpenicillamine (SNAP), 10-7 m ADO, 10 mm KCl) applied sequentially and simultaneously, and observed the response in the associated upstream 4A arteriole controlling the perfusion of the stimulated capillary. We found that KCl significantly attenuated SNAP- and ADO-induced vasodilatations by ∼49.7% and ∼128.0% respectively and ADO significantly attenuated KCl- and SNAP-induced vasodilatations by ∼94.7% and ∼59.6%, respectively. NO significantly attenuated KCl vasodilatation by 93.8%. Further, during muscle contraction we found that inhibition of NO production using l-NG -nitroarginine methyl ester and inhibition of ADO receptors using xanthine amine congener was effective at inhibiting contraction-induced vasodilatation but only in the presence of K+ release channel inhibition. Thus, only when the inhibiting vasodilator K+ was blocked was the second vasodilator, NO or ADO, able to produce effective vasodilatation. Therefore, we show that there are inhibitory interactions between specific Vasodilators at the level of the capillary. Further, these inhibitions can be observed during muscle contraction indicating that redundancies between Vasodilators are physiologically relevant and influence vasodilatation during active hyperaemia.

  • potassium inhibits nitric oxide and adenosine arteriolar vasodilatation via kir and na k atpase implications for redundancy in active hyperaemia
    The Journal of Physiology, 2015
    Co-Authors: Iain R Lamb, Coral L Murrant
    Abstract:

    Key points Multiple Vasodilators have been identified as being important in matching blood flow to the metabolism of contracting skeletal muscle and it has been hypothesized that this process is governed by redundancy between Vasodilators, where one vasodilator can compensate for the loss of another. In the present study, we aimed to determine whether redundancy between Vasodilators exists by investigating whether Vasodilators relevant to skeletal muscle contraction can inhibit the effects of other Vasodilators. We show that potassium can inhibit vasodilatations induced by adenosine and nitric oxide, and also that adenosine and nitric oxide can interact in a way that changes over time. Furthermore, we show that inward rectifying potassium channels and Na+/K+ATPase are partially mechanistically responsible for the interaction between potassium and adenosine and nitric oxide. Our data provide proof of principle that Vasodilators relevant to muscle contraction interact and also that redundancy may govern the processes of active hyperaemia. Abstract Redundancy, in active hyperaemia, where one vasodilator can compensate for another if the first is missing, would require that one vasodilator inhibits the effects of another; therefore, if the first vasodilator is inhibited, its inhibitory influence on the second vasodilator is removed and the second vasodilator exerts a greater vasodilatory effect. We aimed to determine whether Vasodilators relevant to skeletal muscle contraction [potassium chloride (KCl), adenosine (ADO) and nitric oxide] inhibit one another and, in addition, to investigate the mechanisms for this interaction. We used the hamster cremaster muscle and intravital microscopy to directly visualize 2A arterioles when exposed to a range of concentrations of one vasodilator [10−8 to 10−5 m S-nitroso-N-acetyl penicillamine (SNAP), 10−8 to 10−5 m ADO, 10 and 20 mm KCl] in the absence and then in the presence of a second vasodilator (10−7 m ADO, 10−7 m SNAP, 10 mm KCl). We found that KCl significantly attenuated SNAP-induced vasodilatations by ∼65.8% and vasodilatations induced by 10−8 to 10−6 m ADO by ∼72.8%. Furthermore, we observed that inhibition of KCl vasodilatation, by antagonizing either Na+/K+ ATPase using ouabain or inward rectifying potassium channels using barium chloride, could restore the SNAP-induced vasodilatation by up to ∼53.9% and 30.6%, respectively, and also restore the ADO-induced vasodilatations by up to ∼107% and 76.7%, respectively. Our data show that Vasodilators relevant to muscle contraction can interact in a way that alters the effectiveness of other Vasodilators. These data suggest that active hyperaemia may be the result of complex interactions between multiple Vasodilators via a redundant control paradigm.

  • potassium inhibits nitric oxide and adenosine arteriolar vasodilatation via kir and na k atpase implications for redundancy in active hyperaemia
    The Journal of Physiology, 2015
    Co-Authors: Iain R Lamb, Coral L Murrant
    Abstract:

    Redundancy, in active hyperaemia, where one vasodilator can compensate for another if the first is missing, would require that one vasodilator inhibits the effects of another; therefore, if the first vasodilator is inhibited, its inhibitory influence on the second vasodilator is removed and the second vasodilator exerts a greater vasodilatory effect. We aimed to determine whether Vasodilators relevant to skeletal muscle contraction [potassium chloride (KCl), adenosine (ADO) and nitric oxide] inhibit one another and, in addition, to investigate the mechanisms for this interaction. We used the hamster cremaster muscle and intravital microscopy to directly visualize 2A arterioles when exposed to a range of concentrations of one vasodilator [10(-8) to 10(-5) M S-nitroso-N-acetyl penicillamine (SNAP), 10(-8) to 10(-5) M ADO, 10 and 20 mM KCl] in the absence and then in the presence of a second vasodilator (10(-7) M ADO, 10(-7) M SNAP, 10 mM KCl). We found that KCl significantly attenuated SNAP-induced vasodilatations by ∼65.8% and vasodilatations induced by 10(-8) to 10(-6) M ADO by ∼72.8%. Furthermore, we observed that inhibition of KCl vasodilatation, by antagonizing either Na(+)/K(+) ATPase using ouabain or inward rectifying potassium channels using barium chloride, could restore the SNAP-induced vasodilatation by up to ∼53.9% and 30.6%, respectively, and also restore the ADO-induced vasodilatations by up to ∼107% and 76.7%, respectively. Our data show that Vasodilators relevant to muscle contraction can interact in a way that alters the effectiveness of other Vasodilators. These data suggest that active hyperaemia may be the result of complex interactions between multiple Vasodilators via a redundant control paradigm.

Stefan P Mortensen - One of the best experts on this subject based on the ideXlab platform.

  • vasodilator interactions in skeletal muscle blood flow regulation
    The Journal of Physiology, 2012
    Co-Authors: Ylva Hellsten, Michael Nyberg, Lotte Jensen, Stefan P Mortensen
    Abstract:

    During exercise, oxygen delivery to skeletal muscle is elevated to meet the increased oxygen demand. The increase in blood flow to skeletal muscle is achieved by Vasodilators formed locally in the muscle tissue, either on the intraluminal or on the extraluminal side of the blood vessels. A number of Vasodilators have been shown to bring about this increase in blood flow and, importantly, interactions between these compounds seem to be essential for the precise regulation of blood flow. Two compounds stand out as central in these vasodilator interactions: nitric oxide (NO) and prostacyclin. These two Vasodilators are both stimulated by several compounds, e.g. adenosine, ATP, acetylcholine and bradykinin, and are affected by mechanically induced signals, such as shear stress. NO and prostacyclin have also been shown to interact in a redundant manner where one system can take over when formation of the other is compromised. Although numerous studies have examined the role of single and multiple pharmacological inhibition of different vasodilator systems, and important Vasodilators and interactions have been identified, a large part of the exercise hyperaemic response remains unexplained. It is plausible that this remaining hyperaemia may be explained by cAMP- and cGMP-independent smooth muscle relaxation, such as effects of endothelial derived hyperpolarization factors (EDHFs) or through metabolic modulation of sympathetic effects. The nature and role of EDHF as well as potential novel mechanisms in muscle blood flow regulation remain to be further explored to fully elucidate the regulation of exercise hyperaemia.

George Osol - One of the best experts on this subject based on the ideXlab platform.

  • influence of constriction wall tension smooth muscle activation and cellular deformation on rat resistance artery vasodilator reactivity
    Cellular Physiology and Biochemistry, 2012
    Co-Authors: Ilsley Colton, Maurizio Mandala, Jude S Morton, Sandra T Davidge, George Osol
    Abstract:

    This study investigated how vasoconstriction (tone), wall tension, smooth muscle activation, and vascular wall deformation influence resistance artery vasodilator reactivity. Resistance arteries, from two different regional circulations (splanchnic, uterine) and from pregnant and non-pregnant rats, were cannulated and pressurized, or mounted on a wire myograph under isometric conditions prior to being exposed to both endothelium-dependent (acetylcholine, ACh) and -independent (sodium nitroprusside, SNP) vasodilator agonists. A consistent pattern of reduced vasodilator sensitivity was noted as a function of extent of preconstriction for both agonists noted in pressurized arteries. A similar pattern regarding activation was noted in wire-mounted arteries in response to SNP but not ACh. Wall tension proved to be a major determinant of vascular smooth muscle vasodilator reactivity and its normalization reversed this pattern, as more constricted vessels were more sensitive to ACh relaxation without any change in SNP sensitivity, suggesting that endothelial deformation secondary to vasoconstriction augments its vasodilator output. To our knowledge, this is the first study to dissect out the complex interplay between biophysical forces impinging on VSM (pressure, wall tension), the ambient level of tone (vasoconstriction, smooth muscle cell activation), and consequences of cellular (particularly endothelial) deformation secondary to constriction in determining resistance artery vasodilatory reactivity.

Svenerik Ricksten - One of the best experts on this subject based on the ideXlab platform.

  • vasodilator therapy after heart transplantation effects of inhaled nitric oxide and intravenous prostacyclin prostaglandin e1 and sodium nitroprusside
    Journal of Heart and Lung Transplantation, 1995
    Co-Authors: N Kielerjensen, S Lundin, Svenerik Ricksten
    Abstract:

    Background : Vasodilator therapy is frequently needed to treat pulmonary hypertension after heart transplantation. In the present study, the effects of intravenous sodium nitroprusside, prostacyclin, prostaglandin E 1 , and inhaled nitric oxide (5, 10, and 20 parts per million) on central hemodynamics, right ventricular function, and pulmonary selectivity were evaluated shortly after heart transplantation. Methods : Hemodynamic measurements were made after surgery in the intensive care unit. The intravenous Vasodilators were compared at equipotent infusion rates. Effects of inhaled nitric oxide were measured after 10 minutes inhalation at each dose level. Results : Cardiac output, stroke volume, right ventricular end-diastolic volume, and central filling pressures were highest with prostacyclin (16 ± 2 ng/kg/min) compared with both prostaglandin E 1 (202 ± 27 ng/kg/min) and sodium nitroprusside (1.0 ± 0.2 μg/kg/min). Systemic and pulmonary vascular resistance were lowest with prostacyclin. None of the intravenous Vasodilators induced a selective pulmonary vasodilation. In contrast, nitric oxide inhalation induced a selective decrease in pulmonary vascular resistance, with no change in systemic vascular resistance. Cardiac output increased with nitric oxide, whereas mean pulmonary arterial pressure, transpulmonary pressure gradient, and central venous pressure decreased, with the most pronounced effect at an inhaled concentration of 20 parts per million. Conclusions : Prostacyclin is the best choice for intravenous vasodilator therapy after heart transplantation. However, inhaled nitric oxide is the only selective pulmonary vasodilator, which should be used in cases of pulmonary hypertension and severe right ventricular failure associated with systemic hypotension. J HEART LUNG TRANSPLANT 1995 ;14 :436-43.