Contribution of local blood flow regulation mechanisms during head-up tilt in human subcutaneous tissue

Local and remote regulation of subcutaneous blood flow in the forearm and leg was studied during head-up tilt (30°, 457deg; and 70°) in 7 young healthy subjects. Relative blood flow was estimated by the local ¹³³Xe washout technique. Incremental levels of head-up tilt elicited increasing vascular resistance on arm and leg, respectively. Positive pressure similar to a blood column of the same height was able to prevent a significant part of the vasoconstrictor response on the leg to head-up tilt. Thus if venous distension is prevented the local veno-arteriolar reflex is abolished, whereas arteriolar constriction due to centrally elicited reflexes remains unaffected. Subcutaneous blood flow in the extremities are regulated by remote (baroreceptor) as well as local sympathetic reflex mechanisms (veno-arteriolar reflex); but the relative influence of the local veno-arteriolar reflex on the increase in total peripheral resistance seems to decrease with increasing tilt angles.     

Effect of spinal sympathetic blockade upon local regulation of blood flow in subcutaneous tissue.

The influence of spinal sympathetic blockade upon local regulation of blood flow in subcutaneous adipose tissue was investigated in six subjects. The effect of changes in orthostatic pressure on blood flow in subcutaneous tissue in the crus and distal forearm was measured before and after sympathetic blockade obtained by epidural anesthesia in 4 subjects and by a bilateral sympathectomy in 2 patients suffering from manual hyperhidrosis. Blood flow in subcutaneous tissue measured by 133Xe washout technique decreased by about 40 per cent when the limb was lowered, and remained constant during 30 cm elevation. This was found both before and after the blockade, though in one of the patients, the orthostatic decrease in blood flow was less pronounced 24 h after sympathectomy. Hence central sympathetic reflexes do not alter local orthostatic changes of blood flow in subcutaneous tissue. These changes therefore are most likely due to local mechanisms.     

Changes in the local cerebral blood flow accompanying elevation of the systemic arterial pressure in animals

The systemic arterial pressure was raised in normal rabbits and in rabbits with experimental renal hypertension by intravenous injection of noradrenalin and the local cerebral blood flow was recorded at two points of the cortex or white matter of the cerebral hemispheres by the hydrogen-clearance method, and the EEG also was recorded. A series of successive changes in the local cerebral blood flow was observed and these changes could be similar or different in duration and character at different electrodes. Pathological forms of activity were revealed on the EEG.     

Sympathetic nerve regulation of cochlear blood flow during increases in blood pressure in humans

The purpose of this work was to show that regulation of the blood flow to the cochlea by the sympathetic nervous system occurs in humans at the level of the cochlear microcirculation during increases in blood pressure and that its involvement depends on the pressure level. Eight anaesthetized patients undergoing tympanoplasty for hearing disease took part in a pharmacological protocol of stimulation and inhibition of the autonomic nervous system (ANS) to provide variations in systolic blood pressure (BP_S) and cochlear blood flow (CBF). The CBF was measured by laser-Doppler flowmetry. Changes in autonomic nerve activity were brought about by changes in baroreceptor activity (BR) initiated by the injection of an α adrenergic agent before and after sympathetic and parasympathetic blockade. The CBF variations (δCBF) were plotted against BP_S increases at each stage of the ANS inhibition. The BR diminished significantly after α blockade, after α and β blockade, and after α and β blockade and atropine, by 50% (P?P?P?S increased significantly (P?S exhibited two opposing variations in the patients: CBF decreased significantly in one group, and increased significantly in the other group. In both groups, δCBF decrease and δCBF increase, respectively, were significant after ANS blockade; even so the decrease and increase, respectively, levelled off at BP_S around 160 mmHg before ANS blockade. For BP_S below 160 mmHg, correlations between δCBF and BP_S were significant before inhibition and after inhibition of ANS. For BP_S above 160 mmHg, BP_S and δCBF were not correlated before inhibition of ANS, and were significantly correlated after inhibition of ANS. For BP_S below 160 mmHg, CBF response to the BP_S increase was the same before and after ANS blockade, i.e. ANS control did not predominate; even so, for BP_S above 160 mmHg, the CBF response to BP_S increase was different before and after ANS blockade: CBF varied significantly after ANS blockade as it varied for BP_S below 160 mmHg, while it remained constant before ANS blockade that elicited ANS control of CBF. In conclusion, sympathetic nerve regulation via its vasomotor tone at the level of cochlear microcirculation occurred markedly when the blood pressure was above 160 mmHg; the autonomic nervous system would appear to control the cochlear blood flow against large variations in blood flow in response to hypertensive phenomena.     

Oxygen transport: interrelationship between arterial pressure regulation and blood flow autoregulation.

An oxygen transport model was used to study the effects of blood flow autoregulation and arterial pressure regulation on tissue oxygen delivery. At low to moderate levels of oxygen consumption, autoregulatory increases in blood flow act in conjunction with increased tissue diffusing capacity to maintain oxygen delivery as oxygen demand becomes increased. However, an increase in the arterial pressure becomes necessary to augment oxygen delivery at higher levels of oxygen usage. At exercise levels approaching the "maximum aerobic oxygen consumption' rate, arterial pressure regulation appears to be as important as autoregulation for maintaining delivery of oxygen to the tissues. The total negative feedback gain for autoregulatory control of tissue oxygenation varies with the rate of tissue oxygen uptake and is almost 2.0 at the maximum aerobic oxygen consumption rate. Furthermore, the feedback gain is only slightly affected by changes in the mean arterial pressure that occur normally during strenuous exercise, which is indicative of the complementary relationship between these two important control mechanisms.     

Control of muscle blood flow during exercise: local factors and integrative mechanisms

Understanding the control mechanisms of blood flow within the vasculature of skeletal muscle is clearly fascinating from a theoretical point of view due to the extremely tight coupling of tissue oxygen demands and blood flow. It also has practical implications as impairment of muscle blood flow and its prevention/reversal by exercise training has a major impact on widespread diseases such as hypertension and diabetes. Here we analyse the role of mediators generated by skeletal muscle activity on smooth muscle relaxation in resistance vessels in vitro and in vivo. We summarize their cellular mechanisms of action and their relative roles in exercise hyperaemia with regard to early and late responses. We also discuss the consequences of interactions among mediators with regard to identifying their functional significance. We focus on (potential) mechanisms integrating the action of the mediators and their effects among the cells of the intact arteriolar wall. This integration occurs both locally, partly due to myoendothelial communication, and axially along the vascular tree, thus enabling the local responses to be manifest along an entire functional vessel path. Though the concept of signal integration is intriguing, its specific role on the control of exercise hyperaemia and the consequences of its modulation under physiological and pathophysiological conditions still await additional analysis.     

Contribution of calcium-activated chloride channel to elevated pulmonary artery pressure in pulmonary arterial hypertension induced by high pulmonary blood flow

The correlation between calcium-activated chloride channel (CaCC) and pulmonary arterial hypertension (PAH) induced by high pulmonary blood flow remains uncertain. In this study, we investigated the possible role and effects of CaCC in this disease. Sixty rats were randomly assigned to normal, sham, and shunt groups. Rats in the shunt group underwent abdominal aorta and inferior vena cava shunt surgery. The pulmonary artery pressure was measured by catheterization. Pathological changes, right ventricle hypertrophy index (RVHI), arterial wall area/vessel area (W/V), and arterial wall thickness/vessel external diameter (T/D) were analyzed by optical microscopy. Electrophysiological characteristics of pulmonary arterial smooth muscle cells (PASMCs) were investigated using patch clamp technology. After 11 weeks of shunting, PAH and pulmonary vascular structural remodeling (PVSR) developed, accompanied by increased pulmonary pressure and pathological interstitial pulmonary changes. Compared with normal and sham groups, pulmonary artery pressure, RVHI, W/V, and T/D of the shunt group rats increased significantly. Electrophysiological results showed primary CaCC characteristics. Compared with normal and sham groups, membrane capacitance and current density of PASMCs in the shunt group increased significantly, which were subsequently attenuated following chloride channel blocker niflumic acid (NFA) treatment. To conclude, CaCC contributed to PAH induced by high pulmonary blood flow and may represent a potential target for treatment of PAH.     

Contribution of nitric oxide to cerebral blood flow regulation under hypoxia in rats

This study was designed to clarify whether nitric oxide (NO) participates in the regulation of local cerebral blood flow (CBF) during hypoxia (inhalation of 15% O₂ in N₂). The CBF response to hind-paw stimulation (evoked CBF) of Sprague-Dawley (SD) rats was measured by laser-Doppler flowmetry. Physiological variables, such as heart rate, mean blood pressure, and PaCO₂ during hypoxia, were identical to those under normoxic conditions. Hypoxia increased the baseline CBF (17.5 ± 14.3%) and the normalized peak amplitude of evoked CBF (31.1 ± 18.5%) relative to those during normoxia. When an NOS inhibitor was infused intravenously, these differences were abolished in both the baseline CBF or evoked CBF between normoxic and hypoxic conditions, whereas the heart rate decreased and the mean blood pressure increased during hypoxia in comparison with these during normoxia. The field potential was constant under all experimental conditions. These results suggest that NO plays a major role in the regulation of baseline and evoked CBF during hypoxia.     

Effect of lower body negative pressure upon local regulation of blood flow in human subcutaneous tissue

Local regulation of subcutaneous blood flow in the forearm was studied during lower body negative pressure (LBNP) in 7 young healthy male subjects in supine position. Blood flow was measured on the forearm by the local ¹³³Xe washout technique. LBNP of -40 and -60 mmHg induced a decrease in the ¹³³Xe washout rate of 34 and 50% respectively. This response to LBNP could be blocked by proximal nervous blockade indicating that the vasoconstriction observed was due to a central sympathetic reflex mechanism. The vasoconstrictor response to increase in venous transmural pressure induced by lowering the arm (veno-arteriolar reflex mechanism) could not be demonstrated during 40 mmHg LBNP. The abolishment of this reflex is most likely due to centrally elicited increase in sympathetic activity as a normal veno-arteriolar reflex was elicited following proximal nervous blockade.     

Adrenergic mechanisms and blood pressure regulation in diabetes mellitus

Summary Changes in blood pressure (BP) and plasma norepinephrine (NE) following various stimuli of the sympathetic nervous system were studied in six healthy subjects and in 17 diabetic patients. The latter were subdivided in three groups: (1) six patients with neither peripheral neuropathy nor autonomic dysregulation, (2) six patients with severe peripheral neuropathy without autonomic dysregulation, and (3) five patients with autonomic dysregulation, three of whom suffered also from peripheral neuropathy. The following procedures were performed: (1) cold pressor test (2 min), (2) mechanical irritation of the skin by suction (0.75 kg/cm², 10 min), (3) orthostasis (10 min), and (4) i.v. infusion of NE (50, 100, 200 ng kg^–1 min^–1 for 15 min each). Both the stimulated endogenous plasma NE levels and BP response to exogenous NE were the same in normal subjects, in diabetic controls and in diabetics with peripheral neuropathy without autonomic dysregulation. In contrast, diabetics with postural hypotension showed a less pronounced release of NE to standing (P<0.05), but not to cold pressor test and mechanical skin irritation. Furthermore, they showed increased vasoreactivity to the highest dose (P<0.05), but not to the lower doses of exogenous NE. Thus NE release and adrenergic BP regulation seem to be altered only in diabetics with clinical signs of autonomic dysregulation. These alterations can only be evaluated when patients are exposed to stimuli of higher intensity, such as orthostasis or infusion of a high NE dose.     

The effect of angiotensin AT1 receptor blockade in the brain on the maintenance of blood pressure during haemorrhage in sheep

The effect of systemic or intracerebroventricular (ICV) infusion of the angiotensin AT₁ receptor antagonist losartan on blood pressure during hypotensive haemorrhage was investigated in five conscious sheep. Mean arterial pressure (MAP) was measured during haemorrhage (15 mL kg^?1 body wt). Losartan (1 or 0.33 mg h^?1) was given to sheep by ICV, intravenous or intracarotid administration, beginning 60 min before and continuing during the haemorrhage. During control infusion of ICV artificial cerebrospinal fluid, MAP was maintained until 13.16 ± 0.84 mL kg^?1 blood loss, when a rapid reduction of at least 15 mmHg in arterial pressure occurred (the decompensation phase). ICV infusion of losartan at 1 mg h^?1 caused an early onset of the decompensation phase after only 9.8 ± 0.8 mL kg^{? 1} of blood loss compared with control. Intravenous infusion of losartan (1 mg h^?1) also caused an early onset (P < 0.05) of the decompensation phase at 10.2 ± 1.0 mL kg^?1 blood loss. This dose of losartan inhibited the pressor response to ICV angiotensin II, but not to intravenously administered angiotensin II, indicating that only central AT₁ receptors were blocked. Bilateral carotid arterial administration of losartan at 0.33 mg h^?1 caused an early onset of the decompensation phase during haemorrhage at 11.06 ± 0.91 mL kg^?1 blood loss (P < 0.05), which did not occur when infused by intravenous or ICV routes. The results indicate that an angiotensin AT₁-receptor-mediated mechanism is involved in the maintenance of MAP during haemorrhage in sheep. The locus of this mechanism appears to be the brain.