Effect of tyramine on the cerebrovascular resistance and arterial pressure during the action of prostaglandins E

A resistographic study of the cerebrovascular resistance (CVR) and of the arterial blood pressure showed prostaglandins (PG), type E, to inhibit the pressor action of tyramine on the cerebral vessels and the blood pressure. Indomethacin--an inhibitor of PG biosynthesis, retarded the tyramine tachyphylaxis and restored its pressor effect. Ipraside, the monoaminooxidase inhibitor, failed to influence the speed of tyramine tachyphylaxis development under conditions of indomethacin infusion, but increased the pressor effect of tyramine. It is supposed that inomethacin influence was based on the hypersensitivity of the vascular adrenoreceptors.     

Endogenous production of prostaglandins E and F2-alpha in cerebral and extracerebral vessels of cats and its change under the effect of noradrenaline]

The quantitative determination of prostaglandins (PG) E and F2 alpha has been carried out in isolated cerebral and extracerebral vessels of cats. It has been found that the basal production of PG predominates in cerebral vessels, the content of PGF2 alpha prevailing compared to PGE. The incubation of isolated vessels with noradrenaline causes a decrease in production of vasopressor PGF2 alpha with a simultaneous considerable increase in the content of vasodepressor PGE. The changes indicated are especially clearly seen in the cerebral vessels. It is suggested that the level of endogenic production of PG in the cerebral vessels may play an important role in the local regulation of the vascular tone, while the disbalance of their dynamic correlation may be responsible for cerebrovascular abnormalities.     

Effect of aminazine on cerebral circulation]

In acute experiments on anesthetized cats intravenous injection of chloromazine (2--3 mg/kg) caused a reduction in the tone of the cerebral vessels and decreased the general arterial pressure. The cerebral blood circulation increased with the stable arterial pressure or its moderate decrease. With a significant fall of arterial pressure the cerebral blood flow proved to decrease.     

Effect of adrenoblockaders on vascular reactions in sinocarotid baroreflexes]

Blood pressure in the common carotid artery, the tone of the cerebral and femoral vessels were recorded by resistography in acute experiments on nonanesthetized cats (local anesthetics, listenon) with artificial respiration. The increased pressure in isolated carotid sinuses was accompanied by a decrease in arterial pressure and in the tone of the cerebral and femoral vessels. In both cases the reaction of the cerebral vessels was less pronounced as compared to that shown by the femoral vessels. The blocking of alpha-adrenoreceptors with phentolamine reduced or abolished completely the reactions noted. After beta-adrenergic blockade with obsidan these reactions persisted. The role of carotid baroceptors in the regulation of cerebral circulation under orthostatic collapse is discussed.     

Interaction of prostaglandins and the myogenic factor in the mechanism of closure of the ductus arteriosus

Although the role of prostaglandins (PG) in the mechanism of dilatation of the ductus arteriosus (DA) has received considerable attention, no data on their possible interaction with the pressure-induced myogenic reaction are available. There is also a lack of information on PG production by the foetal blood vessels of the guinea-pig, in which the DA closes rapidly. Use of the RIA method showed relatively low PG production by isolated foetal guinea pig blood vessels, as represented by the main products, PGI1 and PGE2. When computed in pmol per mg wet weight, the production of 6-keto-PGF1 alpha (an equivalent of PGI2) was statistically significantly higher in the foetal DA (4.06 +/- 1.13) than in the foetal aorta (2.04 +/- 0.33). The isolated DA reacts to a sudden increase in perfusion pressure by marked constriction, which in some cases leads to functional closure of the DA. In 10(-7) to 10(-5) mol.l-1 concentration, PGE2 reversibly inhibits pressure-induced myogenic constriction, while under the same conditions the contractility of the DA in response to oxygen is unaffected. In concentrations of 10(-6)-10(-5) mol.l-1, indomethacin, a blocker of PG biosynthesis, also induces pressure constriction and it raises the basal flow resistance of isolated DA preparations. The results indicate that PGs play a modulator role in the pressure myogenic response of the DA of guinea-pig and rabbit foetuses.     

The blood-brain barrier: an alternative hypothesis

Brain blood vessels, unlike most vessels elsewhere in the body, exhibit a blood-brain barrier (BBB) to certain substances, e.g. trypan blue. Under some circumstances this barrier is no longer effective and the permeability of the vessels increases. Although capillarization is much less in the brain than in many other organs, e.g. heart muscle, total cerebral blood flow per minute is enormous. Consequently, to accommodate a large blood volume with a limited capillary bed, the velocity of blood through brain vessels must be extremely fast. The hypothesis presented in this paper is that this rapid flow results in a low or negative pressure on the endothelium, and plasma and trypan blue are prevented from passing through the wall. The tight junctions of cerebral endothelial cells may be able to withstand only a limited amount of pressure on their luminal surface. If the velocity of blood in brain capillaries decreases, pressure on the endothelium should increase, and brain vessels, like blood vessels elsewhere in the body, become permeable to vital dyes. Other conditions also increase capillary permeability, e.g. acute arterial hypertension or venous congestion. Although brain vessels can adapt to a moderate, gradual change in systemic pressure, when a significant rise in cerebral arterial pressure is abrupt, the compensatory changes in the postcapillary venous bed may be inadequate and consequently intracapillary pressure and vascular permeability are increased. Venous congestion increases intracapillary pressure by restricting capillary outflow as well as by reducing velocity through capillary beds. Under such conditions increased capillary permeability may be indicated by cerebral edema, and even, on occasion, by petechial hemorrhages. In short, if the flow is fast and unimpeded the BBB will be effective; if the velocity decreases, or intracapillary pressure increases for whatever reason, the permeability of the brain endothelium will be abnormally increased.     

Study of human cerebral blood flow by corrosion casts of the carotid system

20 corrosion casts of human anterior cerebral arteries and middle cerebral arteries were analyzed. In 588 vessel sections in between 2 bifurcations, the relation of vessel length and vessel diameter was investigated. Measurements were taken starting from the arterial trunk down to vessels with a diameter of 0.4 mm. The mean values of the lengths show that both the anterior cerebral artery and the middle cerebral artery can be grouped into 5 diameter ranges with significant different lengths. With decreasing diameter there are short vessels in the groups 1, 3 and 5 and long vessels in the groups 2 and 4. However, the long branches in the groups 2 and 4 of the middle cerebral artery are longer and thinner than in the anterior cerebral artery. Due to the higher pressure loss in thin and long vessels, blood pressure drop occurs earlier in the branches of the middle cerebral artery than in those of the anterior cerebral artery.     

Prostaglandin profiles in nervous tissue and blood vessels of the brain of various animals

The endogenous formation of prostaglandin (PG) D2, E2, F2 alpha, and 6-keto-PGF1 alpha was determined in homogenates of mouse, rat, and rabbit brain, and of rat cerebral blood vessels, using gas chromatography mass spectrometry. In all species tested, 6-keto-PGF1 alpha could be identified in the brain homogenates, but was a minor component in relation to other PGs. In contrast 6-keto-PGF1 alpha was the most abundant PG in the blood vessels, being present in about 40-fold higher levels than in the brain tissue. PGD2 was the most abundant PG in rat and mouse brains, but was below detection limits in the analyzed blood vessels. These studies indicating differential metabolism of PG endoperoxides in nervous and vascular tissue, provide a biochemical basis for further studies on the role of the PGs in brain circulation and neuronal activity.     

Effects of arachidonic acid and prostaglandins on lung function in the intact dog

The effects of the prostaglandin (PG) precursor, arachidonic acid (AA), and the primary PG's, PGF2alpha, and PGD2, on lung function were compared in 39 intact-chest, paralyzed, artificially ventilated dogs. Intravenous AA decreased dynamic compliance (Cdyn) and functional residual capacity and increased airway resistance (Rl) and transpulmonary pressure at end-passive expiration. The decrease in Cdyn correlated closely with a rise in pulmonary arterial pressure (Ppa). Indomethacin abolished airway and vascular responses to AA, but did not attenuate responses to the PG's. The effects of AA, PGD2, and PGF2alpha on lung function and Ppa were similar, whereas PGE2 had little effect. Vagotomy attentuated the RL increase in response to AA, PGE2alpha, and PGD2 and the Cdyn decrease in response to the PG's. The effects of the PG's on compliance were greater than those produced by mechanically increasing pulmonary venous pressure. The present studies suggest that the PG precursor is rapidly converted to agents that have marked effect on both pulmonary vessels and airways, particularly peripheral airways, in the dog.     

Lumped Parameter and Feedback Control Models of the Auto-regulatory Response in the Circle of Willis

The Circle of Willis (CoW) is a ring-like structure of blood vessels found beneath the hypothalamus at the base of the brain. Its main function is to distribute oxygen-rich arterial blood to the cerebral mass. A 1-dimensional model of the CoW has been created to simulate a series of possible clinical scenarios such as occlusions in afferent arteries, absent or string-like circulus vessels, or arterial infarctions. The model captures cerebral haemodynamic auto-regulation by using a proportional-integral-derivative (PID) controller to modify efferent resistances and maintain optimal efferent flowrates for a given circle geometry and afferent blood pressure. Results match limited clinical data and results obtained in prior studies to within 6%. In addition, a set of boundary conditions and geometry is presented for which the auto-regulated system cannot provide the necessary efferent flowrates and perfusion, representing a condition with increased risk of stroke and highlighting the importance of modelling the haemodynamics of the CoW. The system model created is computationally simple so it can be used to identify at-risk cerebral arterial geometries and conditions prior to surgery or other clinical procedures.     

Effect of sodium hydroxybutyrate on cerebral circulation and regional vasomotor reflexes

In experiments on cats it was found using electromagnetic and resistographic methods that sodium hydroxybutyrate (100 mg/kg) considerably increases cerebral circulation. The drug also potentiates the blood flow to the brain during formation of pressor reflexes of the arterial pressure. The blood flow increase is also observed in the system of femoral arteries while in the intestinal artery, on the contrary, there is a reduction in the blood flow increase during vasomotor reflexes. The reflex changes of the resistance in regional vessels are also different: the inhibition of pressor reflexes in the cerebral vessels along with their facilitation in the intestinal and femoral arteries and the potentiation of the reflex dilatatory phase in the limb vessels are seen. Different sensitivity to the drug of synaptic formations in the central links of various regional vasomotor reflexes is likely to underlie the difference described.     

Lumped parameter and feedback control models of the auto-regulatory response in the Circle of Willis

The Circle of Willis (CoW) is a ring-like structure of blood vessels found beneath the hypothalamus at the base of the brain. Its main function is to distribute oxygen-rich arterial blood to the cerebral mass. A 1-dimensional model of the CoW has been created to simulate a series of possible clinical scenarios such as occlusions in afferent arteries, absent or string-like circulus vessels, or arterial infarctions. The model captures cerebral haemodynamic auto-regulation by using a proportional-integral-derivative (PID) controller to modify efferent resistances and maintain optimal efferent flowrates for a given circle geometry and afferent blood pressure. Results match limited clinical data and results obtained in prior studies to within 6%. In addition, a set of boundary conditions and geometry is presented for which the auto-regulated system cannot provide the necessary efferent flowrates and perfusion, representing a condition with increased risk of stroke and highlighting the importance of modelling the haemodynamics of the CoW. The system model created is computationally simple so it can be used to identify at-risk cerebral arterial geometries and conditions prior to surgery or other clinical procedures.     

The role of prostaglandins in the development of cardio- and hemodynamic disorders in postischemic shock

Experiments on anaesthetized dogs have shown, that reperfusion of ischemized tissues is accompanied by significant increase in thromboxane A2 (Tx A2) and prostacyclin (PG I2) blood level and by development of pronounced cardiovascular insufficiency. Preliminary blockade of prostaglandins biosynthesis prevent an increase of TbA2 and PG12 blood level, postreperfusion disturbances of central and regional circulation develop later and are less pronounced. Therefore, endogenic prostaglandins take part in the development of post ischemic shock reaction, influencing chiefly the venous vessels and blood return to heart.     

One-dimensional and three-dimensional models of cerebrovascular flow

The Circle of Willis is a ring-like structure of blood vessels found beneath the hypothalamus at the base of the brain. Its main function is to distribute oxygen-rich arterial blood to the cerebral mass. One-dimensional (1D) and three-dimensional (3D) computational fluid dynamics (CFD) models of the Circle of Willis have been created to provide a simulation tool which can potentially be used to identify at-risk cerebral arterial geometries and conditions and replicate clinical scenarios, such as occlusions in afferent arteries and absent circulus vessels. Both models capture cerebral haemodynamic autoregulation using a proportional-integral (PI) controller to modify efferent artery resistances to maintain optimal efferent flow rates for a given circle geometry and afferent blood pressure. The models can be used to identify at-risk cerebral arterial geometries and conditions prior to surgery or other clinical procedures. The 1D model is particularly relevant in this instance, with its fast solution time suitable for real-time clinical decisions. Results show the excellent correlation between models for the transient efferent flux profile. The assumption of strictly Poiseuille flow in the 1D model allows more flow through the geometrically extreme communicating arteries than the 3D model. This discrepancy was overcome by increasing the resistance to flow in the anterior communicating artery in the 1D model to better match the resistance seen in the 3D results.     

Hypercholesterolemia and the baboon cerebral circulation

We investigated cerebrovascular vasodilator responses to increased arterial CO2 and the cerebrovascular response to infused 5-hydroxytryptamine (5-HT) in normal and hypercholesterolemic baboons. After 6-8 weeks of feeding an atherogenic diet the plasma cholesterol levels were increased without change in the triglycerides. The hypercholesterolemic animals showed a higher basal systemic arterial blood pressure than the normal controls without significant decrease in cerebrovascular prostacyclin production, altered basal cerebral blood flow or altered cerebrovascular response to infused 5-HT. However, the vasodilator response to hypercapnia was significantly decreased from the control value of 2.78 ml/min per mmHg increase in PCO2, to 1.62 ml/min per mmHg. Thus functional impairment of cerebral hemodynamics occurred before atherosclerotic alteration in the cerebral vessels could have been present.     

Chronic angiotensin II AT1 receptor blockade increases cerebral cortical microvessel density

Angiotensin II is known to stimulate angiogenesis in the peripheral circulation through activation of the angiotensin II type 1 (AT1) receptor. This study investigated the effect of angiotensin receptor blockade on cerebral cortical microvessel density. Rats (6-7 wk old, n = 5-17) were instrumented with femoral arterial and venous indwelling catheters for arterial blood pressure measurement and drug administration. Rats were treated for 3 or 14 days with the AT1 receptor blocker losartan (50 mg/day in drinking water) or vehicle. Brains were sectioned and immunostained for CD31, and microvessel density was measured. Treatment with losartan for 3 or 14 days resulted in a slight decrease in mean arterial blood pressure (3 days, 92 +/- 1 mmHg; and 14 days, 99 +/- 2 mmHg) compared with vehicle (109 +/- 3 and 125 +/- 4 mmHg, respectively). A furosemide + captopril 14-day treatment group was added to control for the blood pressure change (96 +/- 3 mmHg). Microvessel density increased in groups treated with losartan for 14 days (429 +/- 13 vessels/mm2) compared with vehicle (383 +/- 11 vessels/mm2) but did not change with furosemide + captopril (364 +/- 7 vessels/mm2). Thus AT1 receptor blockade for 14 days resulted in increased cerebral microvessel density in a blood pressure-independent manner.     

Proteoglycan synthesis in the endothelium of embryonal vertebrate hearts: significance for the development of cardiovascular function

The endothelium of the embryonic heart is able to synthetize proteoglycans (PG) as it is the myocardium. In the extracellular matrix, PG form highly polymeric visco-elastic networks, which besides others act as shock absorber. That is apparently of evidence for the modulation of embryonic heart actions. Because during the embryonic period the large arteries are simple endothelial tubes without having an elastic-muscular wall. That means the typical "windkessel" function such as dumping of pulse waves or a continues pressure distribution is not existent. The embryonic vessels are perfused like rigid tubes. The continuous rhythmic flow pattern in the endothelial tubes, necessary for perfusion of the different organs, is apparently compensated by a high initial pressure level initiated by the heart. It is concluded that the continuity of the pressure profile is caused by intracardial PG. The endothelial synthesis of the PG of the heart decreases with increasing development of the muscular wall of the vessels and disappears completely post partum.     

Beyond the aorta: partial transmission of reflected waves from aortic coarctation into supra-aortic branches modulates cerebral hemodynamics and left ventricular load

Wave reflection from the site of aortic coarctation produces a reflected backward compression wave (BCW) that raises left ventricular (LV) afterload. However, not all reflected wave power will propagate back to the LV. This study investigated the hypothesis that the BCW is partially transmitted into supra-aortic vessels as a forward wave and explored the consequences of this phenomenon for cerebral and LV haemodynamic load. In eight sheep, high fidelity pressure and flow were measured in the aortic trunk (AoT) and brachiocephalic trunk (BCT, the single supra-aortic vessel present in sheep) at baseline and during two levels of proximal descending aortic constriction. Wave power analysis showed that aortic constriction produced not only a BCW in the AoT, but also a second forward compression wave (\(\mathrm{FCW}_{2})\) in the BCT that augmented pressure and flow after the initial forward compression wave (\(\mathrm{FCW}_{1})\). Mathematical analysis and a one-dimensional model of the human systemic arteries and aortic coarctation suggested that the relative transmission of waves into supra-aortic vessels versus the aorta was determined by the relative admittances of these vessels. Reducing supra-aortic admittance (1) increased pressure and flow pulsatility in cerebral arteries, (2) produced carotid and middle cerebral arterial flow waveforms with an older adult phenotype, (3) promoted transmission of reflected wave power towards the LV and (4) substantially increased mid- to late-systolic myocardial stress, which may promote LV hypertrophy. These findings suggest that wave transmission into supra-aortic branches has an important impact on both cerebral hemodynamics and LV load in aortic coarctation.     

Prostaglandin profiles in nervous tissue and blood vessels of the brain of various animals

The endogenous formation of prostaglandin (PG) D₂, E₂, F_2α, and 6-keto-PGF_1α was determined in homogenates of mouse, rat, and rabbit brain, and of rat cerebral blood vessels, using gas chromatography mass spectrometry. In all species tested, 6-keto-PGF_1α could be identified in the brain homogenates, but was a minor component in relation to other PGs. In contrast 6-keto-PGF_1α was the most abundant PG in the blood vessels, being present in about 40-fold higher levels than in the brain tissue. PGD₂ was the most abundant PG in rat and mouse brains, but was below detection limits in the analyzed blood vessels. These studies indicating differential metabolism of PG endoperoxides in nervous and vascular tissue, provide a biochemical basis for further studies on the role of the PGs in brain circulation and neuronal activity.     

Pressure-induced myogenic tone and role of 20-HETE in mediating autoregulation of cerebral blood flow

While myogenic force in response to a changing arterial pressure has been described early in the 20th century, it was not until 1984 that the effect of a sequential increase in intraluminal pressure on cannulated cerebral arterial preparations was found to result in pressure-dependent membrane depolarization associated with spike generation and reduction in lumen diameter. Despite a great deal of effort by different laboratories and investigators, the identification of the existence of a mediator of the pressure-induced myogenic constriction in arterial muscle remained a challenge. It was the original finding by our laboratory that demonstrated the capacity of cerebral arterial muscle cells to express the cytochrome P-450 4A enzyme that catalyzes the formation of the potent vasoconstrictor 20-hydroxyeicosatetraenoic acid (20-HETE) from arachidonic acid, the production of which in cerebral arterial muscle cells increases with the elevation in intravascular pressure. 20-HETE activates protein kinase C and causes the inhibition of Ca(2+)-activated K(+) channels, depolarizes arterial muscle cell membrane, and activates L-type Ca(2+) channel to increase intracellular Ca(2+) levels and evoke vasoconstriction. The inhibition of 20-HETE formation attenuates pressure-induced arterial myogenic constriction in vitro and blunts the autoregulation of cerebral blood flow in vivo. We suggest that the formation and action of cytochrome P-450-derived 20-HETE in cerebral arterial muscle could play a critically important role in the control of cerebral arterial tone and the autoregulation of cerebral blood flow under physiological conditions.