Conducted vasomotor responses in arterioles: characteristics,mechanisms and physiological significance

Micropipette application of certain vasoconstrictor or -dilator substances onto the surface of arterioles induces both a local vasomotor response and a response which is propagated up- and downstream along the vessel, a so-called conducted vasomotor response. In some vascular beds conducted vasoconstrictor and dilator responses are detectable more than a millimetre from the site of agonist delivery. While agonists such as acetylcholine, noradrenaline, and KCl almost invariably give rise to conducted vasomotor responses others, such as sodium nitroprusside or vasopressin, do not. Conducted vasomotor responses in arterioles appear to rely on passive electrotonic spread of the change in membrane potential induced by the agonist at the tip of the pipette. Presumably the current spreads up- and downstream along the arteriolar wall through endothelial or smooth muscle cell gap junctions. Whether the electrical signal is conducted primarily through the endothelial or the smooth muscle cell layer or both is currently not known, but it may depend on the agonist used. Experiments have suggested that conducted vasodilation in skeletal muscle feed arterioles plays an important role in the development of functional hyperaemia at the onset of exercise. In the kidney, conducted vasoconstriction is believed to be responsible for the upstream contraction of the afferent arteriole and interlobular artery known to occur in response to activation of the macula densa. Therefore conducted vasoconstriction could be important for the tubuloglomerular feedback mechanism. Finally, experimental studies have shown that conduction of vasomotor responses in arterioles may be altered in pathological conditions associated with microvascular dysfunction such as arterial hypertension and sepsis.     

Oxygen sensing and conducted vasomotor responses in mouse cremaster arterioles in situ

This study examines mechanisms by which changes in tissue oxygen tension elicit vasomotor responses and whether localized changes in oxygen tension initiates conducted vasomotor responses in mouse cremaster arterioles. Intravital microscopy was used to visualize the mouse cremaster microcirculation. The cremaster was superfused with Krebs’ solution with different oxygen tensions, and a gas exchange chamber was used to induce localized changes in oxygen tension. In arterioles where red blood cells were removed by buffer perfusion, arterioles responded with same magnitudes of vasodilatation (ΔD?=?16.0?±?4.9 μm) when changing from high (PO₂?=?242.5?±?13.3 mm Hg) to low (PO₂?=?22.5?±?4.8 mm Hg) oxygen tension as seen in the intact cremaster circulation (ΔD?=?18.7?±?1.0 μm). Blockade of NO synthases by L-NAME and adenosine receptors by DPCPX had no effects on vasomotor responses to low or high oxygen. Induction of localized low (PO₂?=?23.3?±?5.7 mmHg) or high (PO₂?=?300.0?±?25.7 mm Hg) oxygen tension caused vasodilatation or -constriction locally and at a site 1,000 μm upstream (distantly). Glibenclamide blocker of ATP-sensitive K⁺ channels inhibited vasodilatation and -constriction to low (PO₂?=?16.0?±?6.4 mm Hg) and high (PO₂?=?337.4?±?12.8 mm Hg) oxygen tension. 1) ATP-sensitive K⁺ channels seem to mediate, at least in part, vasodilatation and vasoconstriction to low and high oxygen tension; 2) Red blood cells are not necessary for inducing vasodilatation and vasoconstriction to low or high oxygen tension; 3) localized changes in the oxygen tension cause vasomotor responses, which are conducted upstream along arterioles in mouse cremaster microcirculation.     

Sex differences in human fatigability: mechanisms and insight to physiological responses

Sex‐related differences in physiology and anatomy are responsible for profound differences in neuromuscular performance and fatigability between men and women. Women are usually less fatigable than men for similar intensity isometric fatiguing contractions. This sex difference in fatigability, however, is task specific because different neuromuscular sites will be stressed when the requirements of the task are altered, and the stress on these sites can differ for men and women. Task variables that can alter the sex difference in fatigability include the type, intensity and speed of contraction, the muscle group assessed and the environmental conditions. Physiological mechanisms that are responsible for sex‐based differences in fatigability may include activation of the motor neurone pool from cortical and subcortical regions, synaptic inputs to the motor neurone pool via activation of metabolically sensitive small afferent fibres in the muscle, muscle perfusion and skeletal muscle metabolism and fibre type properties. Non‐physiological factors such as the sex bias of studying more males than females in human and animal experiments can also mask a true understanding of the magnitude and mechanisms of sex‐based differences in physiology and fatigability. Despite recent developments, there is a tremendous lack of understanding of sex differences in neuromuscular function and fatigability, the prevailing mechanisms and the functional consequences. This review emphasizes the need to understand sex‐based differences in fatigability to shed light on the benefits and limitations that fatigability can exert for men and women during daily tasks, exercise performance, training and rehabilitation in both health and disease.     

Resistance responses in proximal arterial vessels, arterioles and veins during reactive hyperaemia in skeletal muscle and their underlying regulatory mechanisms

The reactive hyperaemia response cat skeletal muscle to 2-120 s arterial occlusions was analysed with regard to amplitude, duration, 'excess blood flow' and site of dilator action along the vascular bed. The last-mentioned was assessed with a new whole-organ technique permitting continuous segmental resistance recordings in arterial vessels greater than 25 microns, arterioles less than 25 microns and veins. Peak amplitude, duration and excess flow all increased with increasing occlusion length, of which excess flow was linearly related to occlusion length. The site of active dilatation was preferentially confined to arterioles less than 25 microns in which complete relaxation was observed after only 20 s occlusion, although the duration of the response continued to increase with more prolonged occlusions. A graded, but less pronounced, dilatation occurred in the arterial vessels greater than 25 microns and in the veins, the former exhibiting a 63% inhibition of tone as a maximum response at 120 s occlusion. The recovery phase was characterized by a vivid active constrictor component apparently protecting the capillaries from excessive pressure load upon arterial occlusion release, but this constriction became attenuated at long occlusions, thereby prolonging the hyperaemia response. The role of myogenic regulatory mechanisms in the responses was assessed from observed segmental resistance reactions to selectively applied transmural pressure stimuli similar to those elicited by arterial occlusion/release. It was concluded that myogenic mechanisms alone could explain the amplitude of the reactive hyperaemia response at short (up to 30 s) occlusions. Metabolic mechanisms seemed to be responsible for further relaxation of the proximal arterial vessels at longer occlusions, and also for the increased duration of the hyperaemia response at occlusions exceeding 10 s. Blockade of nitric oxide formation (endothelium-derived relaxing factor) did not seem to affect the reactive hyperaemia response.     

主动脉处的血流动力学特性及其生理意义

主动脉结构复杂成三维螺旋状,在心脏收缩期该处流动成旋动流态。这种旋动流态也许有着积极的生理意义,能够通过抑制湍流、促进物质传输,从而抑制心血管疾病的发生。引起主动脉处的旋动流主要是左心室收缩的扭曲运动、主动脉的三维空间几何构型、主动脉处的脉动流特征以及主动脉的运动。基于以上研究结果,近年来,研究者们以期将旋动流原理应用于心血管介入治疗和心血管介入器械的设计中。本文就主动脉处的旋动流态观察、其生理意义、引起该旋动流态的原因、及旋动流在临床器械设计中的应用等进行综述。     

The pupillary, the intraocular pressure and the vasomotor responses to noradrenaline in rabbits.

1. A study has been made of the cause of the temporal disparity between the pupillary and intraocular pressure responses to noradrenaline applied topically. 2. Over a 5-day experimental period, the quantitative characteristics of the pupillary response to noradrenaline applied either once or several times daily remained essentially unchanged. In the same rabbits the delay in pressure response to noradrenaline on the first day was increased by a second application and, on subsequent days, multiple applications of noradrenaline induced a biphasic pressure response. 3. Intravenous phenoxybenzamine inhibited both the pupillary and the biphasic pressure responses to noradrenaline. Phenoxybenzamine applied topically inhibited the ocular hypertensive but not the hypotensive and pupillary responses. 4. Analysis of aqueous humour dynamics by manometric procedures showed that the hyper- and hypotensive responses were associated with increase and decrease, respectively, of the resistance to outflow of the aqueous humour.     

Learning of physiological responses: I. Habituation, sensitization, and classical conditioning

Rats with chronic neuromuscular block (NMB) maintained by continuous infusion of alpha-bungarotoxin were classically conditioned. All rats showed reliable discriminative-conditioned tibial nerve firing, hind limb vasoconstriction, hypertension, bradycardia, and electroencephalographic (EEG) desynchronization. A regression analysis indicated that the conditioned vasoconstriction was neither centrally mediated by, nor inextricably linked to, skeletal (tibial) nerve firing. Throughout the experiment there were normal blood gases, pH, Na, serum protein, hematocrit, blood pressure, heart rate, vasomotor tone, and tibial nerve activity. The vital signs, EEG spectra, and cortical evoked potentials reflected regular sleep-wakefulness cycles and responsiveness to mild stimuli. The NMB rat preparation with its stable physiological state and fully intact central nervous system may be a useful model for a variety of physiological, medical, and neurobehavioral studies.     

Bacterial resistance to tetracycline: mechanisms, transfer, and clinical significance.

Tetracycline has been a widely used antibiotic because of its low toxicity and broad spectrum of activity. However, its clinical usefulness has been declining because of the appearance of an increasing number of tetracycline-resistant isolates of clinically important bacteria. Two types of resistance mechanisms predominate: tetracycline efflux and ribosomal protection. A third mechanism of resistance, tetracycline modification, has been identified, but its clinical relevance is still unclear. For some tetracycline resistance genes, expression is regulated. In efflux genes found in gram-negative enteric bacteria, regulation is via a repressor that interacts with tetracycline. Gram-positive efflux genes appear to be regulated by an attenuation mechanism. Recently it was reported that at least one of the ribosome protection genes is regulated by attenuation. Tetracycline resistance genes are often found on transmissible elements. Efflux resistance genes are generally found on plasmids, whereas genes involved in ribosome protection have been found on both plasmids and self-transmissible chromosomal elements (conjugative transposons). One class of conjugative transposon, originally found in streptococci, can transfer itself from streptococci to a variety of recipients, including other gram-positive bacteria, gram-negative bacteria, and mycoplasmas. Another class of conjugative transposons has been found in the Bacteroides group. An unusual feature of the Bacteroides elements is that their transfer is enhanced by preexposure to tetracycline. Thus, tetracycline has the double effect of selecting for recipients that acquire a resistance gene and stimulating transfer of the gene.     

Cross-talk mechanisms in biofilm formation and responses to environmental and physiological stress in Escherichia coli

Switching from single-cell (planktonic) to biofilm growth (and vice versa) is regulated by a variety of environmental and physiological cues. Signals leading to activation of stress responses often lead to biofilm formation which, in turn, can trigger induction of stress response mechanisms, suggesting direct cross-talk between the two cellular processes. Regulatory mechanisms of this process include two-component regulatory systems, master regulators such as the rpoS gene and signal molecules such as cyclic-di-GMP, in a tight and complex interplay.     

Medullary and supramedullary mechanisms regulating sympathetic vasomotor tone

AIM: Neurons in the rostral ventrolateral medulla (RVLM) that project directly to sympathetic preganglionic neurons in the spinal cord play a critical role in maintaining tonic activity in sympathetic vasomotor nerves. Intracellular recordings in vivo from putative RVLM presympathetic neurons have demonstrated that under resting conditions these neurons display an irregular tonic firing rate, and also receive both excitatory and inhibitory synaptic inputs. This paper will briefly review some recent findings on the role of glutamate, GABA and angiotensin II (Ang II) receptors in maintaining the tonic activity of RVLM presympathetic neurons. RESULTS: Based on these findings, the following hypotheses will be discussed: (1) RVLM neurons receive tonic glutamatergic excitatory inputs, which originate from both medullary and supramedullary sources; (2) at least some neurons that project to and tonically inhibit RVLM presympathetic neurons are themselves tonically inhibited by GABAergic inputs originating from neurons in the caudalmost part of the ventrolateral medulla (caudal pressor area); (3) under normal conditions, Ang II receptors in the RVLM do not contribute significantly to the tonic activity of RVLM presympathetic neurons, but may do so in abnormal conditions such as heart failure or neurogenic hypertension; (4) RVLM presympathetic neurons maintain a significant level of tonic resting activity even when glutamate, GABA and Ang II receptors on the neurons are completely blocked. Under these conditions, the tonic activity is a consequence either of the intrinsic membrane properties of the neurons (autoactivity) or of synaptic inputs mediated by receptors other than glutamate, GABA or Ang II receptors. CONCLUSION: The current evidence indicates that the resting activity of RVLM presympathetic neurons is determined by the balance of powerful tonic excitatory and inhibitory synaptic inputs. Ang II receptors also contribute to the raised resting activity of these neurons in some pathological conditions.     

Personality, emotion, and individual differences in physiological responses

A dominant paradigm in biopsychological personality research seeks to establish links between emotional and motivational traits and habitual, transsituationally consistent individual differences in measures of physiological activity. An alternative approach conceptualizes traits as dispositions that are only operative in certain situational contexts and consequently predicts associations between emotional and motivational traits and physiological activity only for trait-relevant situational contexts in which the physiological systems underlying the traits in question are engaged. In the present paper we first examine and contrast these personistic and interactionistic conceptualizations of personality and personality-physiology associations and then present data from several large studies (N > 100) in which electrocortical (e.g., frontal alpha asymmetry) and somatovisceral parameters were measured in various situational contexts (e.g., after the induction of either anger, or fear, or anxiety). As predicted by the interactionistic conceptualization of traits as dispositions the situational context and its subjective representation by the participants moderated the personality-physiology relationships for measures of both central and peripheral nervous system activity. We conclude by outlining the implications of the interactionistic approach for biopsychological personality research.