Acute Arterial Hypertension Research Articles

Effect of diabetes mellitus on disruption of the blood-brain barrier during acute hypertension

The goal of this study was to determine whether the susceptibility of the blood-brain barrier to disruption during acute hypertension is altered during diabetes mellitus. Intravital fluorescent microscopy and fluorescein-labelled albumin were used to evaluate disruption of the blood-brain barrier under control conditions and during acute arterial hypertension in non-diabetic rat and diabetic rats. Permeability of the blood-brain barrier was quantitated by calculating clearance of fluorescent-labelled albumin and by counting the number of microvascular leaky sites under control conditions and during acute hypertension. In non-diabetic rats, when systemic arterial pressure was increased from105 ± 5 (mean±S.E.) to185 ± 8mmHg, clearance of albumin increased from0.16 ± 0.04 to 1 ± 0.34ml/s× 10 −6. In diabetic rats, when systemic arterial pressure was increased from117 ± 3to184 ± 3mmHg, clearance of albumin increased0.22 ± 0.10 to 1.30 ± 0.32ml/s× 10 −6. These findings suggest that the susceptibility of the blood-brain barrier to disruption during acute hypertension is not altered during diabetes mellitus.

Etiology of the disruption in blood-arterial wall barrier following experimental subarachnoid hemorrhage

Aneurysmal subarachnoid hemorrhage is associated with a sudden rise in intracranial pressure, acute arterial hypertension, and subarachnoid blood. The role that each of these factors may play in the development of the acute barrier disruption of the major cerebral arteries following subarachnoid hemorrhage was investigated in 42 rabbits. Horseradish peroxidase was given intravenously to assess the integrity of the barrier by transmission electron microscopy. Permeation of the tracer into the vessel was noted only in animals with increased intracranial pressure. A sudden rise in intracranial pressure is suggested to trigger acute barrier disruption following subarachnoid hemorrhage.

Disruption of blood-brain barrier during acute hypertension in adult and aged rats

The goal of this study was to determine whether the susceptibility of the blood-brain barrier to disruption during acute hypertension is altered in aged rats. Intravital fluorescent microscopy and fluorescein-labeled albumin were used to evaluate disruption of the blood-brain barrier during acute hypertension in adult Wistar rats (6-8 mo) and aged Wistar rats (24-26 mo). Permeability of the blood-brain barrier albumin and by counting the number of microvascular leaky sites under control conditions and during acute arterial hypertension in adult and aged rats. Pressure in pial venules, which are the primary site of disruption of the blood-brain barrier during acute hypertension, and in pial arterioles was measured using a servo-null device. In adult rats, when systemic arterial pressure was increased from 124 +/- 5 (means +/- SE) to 190 +/- 5 mmHg, clearance of albumin increased from 0.10 +/- 0.05 to 1.64 +/- 0.76 X 10(-6) ml/s. In aged rats, when systemic arterial pressure was increased from 116 +/- 4 to 185 +/- 3 mmHg, clearance of albumin increased from 0.10 +/- 0.03 to 1.56 +/- 0.49 X 10(-6) ml/s. Increases in pial venular pressure and pial arteriolar pressure also were similar in adult and aged rats. Thus the findings suggest that the susceptibility of the blood-brain barrier to disruption during acute hypertension is similar in adult and aged rats.

Electrocardiographic changes suggestive of myocardial ischemia elicited by dipyridamole infusion in acute rejection early after heart transplantation.

Acute cardiac rejection, syndrome X, and arterial hypertension can induce small vessel damage and, therefore, restriction of coronary reserve in the presence of normal epicardial coronary arteries. A characteristic response pattern to dipyridamole (DIP) infusion has been previously described in syndrome X and arterial hypertension: ST segment depression without any measurable systolic dysfunction. The aim of this study was to establish whether acute cardiac rejection might induce electrocardiographic alterations during DIP infusion. Changes in the 12-lead electrocardiogram and two-dimensional echocardiogram during high-dose DIP infusion (up to 0.84 mg/kg in 10 minutes) were evaluated within 24 hours of endomyocardial biopsy in 14 transplanted patients. A total of 47 biopsy-controlled DIP studies were performed within 5 weeks after cardiac transplantation. For each patient, at least 7 days elapsed between two consecutive studies. Electrocardiographic and echocardiographic tracings were analyzed without prior knowledge of endomyocardial biopsy findings. No remarkable side effects occurred in any case, so that the DIP study could be completed in all patients. A diagnostic (greater than 0.1 mV) ST segment depression was found in 11 studies. The sensitivity and specificity of DIP-induced ST segment depression for the detection of biopsy-proven acute rejection were 72% and 94%, respectively. These data show that DIP stress is feasible and safe in transplanted patients and that acute cardiac rejection can be accompanied by DIP-induced ST segment depression without detectable impairment in systolic function. These changes might provide noninvasive markers for surveillance of rejection.

Time course of proximal tubule response to acute arterial hypertension in the rat.

Acute hypertension was previously shown to cause partial inhibition of proximal tubule fluid reabsorption in perfused tubules in the rat. If the inhibition also occurs in unobstructed tubules receiving native glomerular filtrate, hypertension should increase end proximal flow rate despite autoregulation of glomerular filtration rate (GFR). We tested this prediction with a videodensitometric method recently developed for measurement of tubular flow rate that does not interrupt flow to the macula densa. Hypertension was induced by increasing total peripheral resistance in rats receiving several hormones at rates designed to maintain high levels of these agents. End proximal flow rate was increased 18% as early as 1.5-2 min following the induction of hypertension and increased over the course of the next 25-30 min to reach values 50% greater than controls as the hypertension was sustained. Whole-kidney GFR and renal blood flow were fully autoregulated. The results confirm that hypertension increases the fluid load to the loop of Henle, and are consistent with an effect on proximal tubule fluid reabsorption. This increase in fluid load could signal the macula densa and contribute to the efficacy of autoregulation; it could also provide a significant fraction of the increased fluid and salt excretion of pressure natriuresis.

Vascular effects of oxygen-derived free radicals

This review attempts to summarize the available data regarding the vascular actions of free oxygen radicals. Studies on blood vessels in situ and in vitro demonstrate that free oxygen radicals can evoke both vasodilation and vasoconstriction. Free oxygen radicals can modulate the tone of vascular smooth muscle by acting directly on the smooth muscle cells, and also via indirect mechanisms by changes in the production or biological activity of vasoactive mediators. The individual oxygen radicals may have different (sometimes opposite) vascular effects. Superoxide anion inactivates endothelium-derived relaxing factor and the adrenergic neurotransmitter norepinephrine. Hydrogen peroxide and the hydroxyl radical evoke vasodilation by acting directly on vascular smooth muscle and also by stimulating the synthesis/release of endothelium-derived relaxing factor. In acute arterial hypertension or experimental brain injury oxygen radicals are important mediators of vascular damage. Production of oxygen-derived free radicals by activated neutrophils may be responsible for vasodilation and increased permeability of capillary membrane during the acute inflammatory process. Free oxygen radicals also play an important role in reperfusion injury of various organs, and vascular actions of the free radicals may contribute to the damage of parenchymal tissues.

Role of veins and cerebral venous pressure in disruption of the blood-brain barrier.

The goal of this study was to determine whether increases in cerebral venous pressure contribute to, and may account for, disruption of the blood-brain barrier during acute hypertension and hyperosmolar stimuli. We studied the relation between pial venous pressure and disruption of the blood-brain barrier during acute arterial hypertension, superior venae cavae occlusion, and superfusion with hyperosmolar arabinose. Sprague-Dawley rats were studied using intravital fluorescent microscopy and fluorescein-labelled dextran (mol. wt. = 70,000). Disruption of the blood-brain barrier was characterized by the appearance of microvascular leaky sites and quantitated by the clearance of fluorescein dextran. We measured pressure (servo null) in pial arterioles and venules 40-60 micron in diameter. Acute hypertension, occlusion of the superior venae cavae, and hyperosmolar arabinose produced leaky sites primarily in venules. Acute hypertension increased arteriolar pressure and also venular pressure, from 7 +/- 1 (mean +/- SE) to 28 +/- 2 mm Hg. Clearance of fluorescein dextran increased from 0.03 +/- 0.01 to 2.90 +/- 0.40 ml/sec X 10(-6). Occlusion of the superior venae cavae increased pial venous pressure from 7 +/- 1 to 30 +/- 3 mm Hg, and clearance of fluorescein dextran, from 0.02 +/- 0.01 to 3.10 +/- 0.59 ml/sec X 10(-6). In contrast to acute hypertension, there was a decrease in arterial and pial arteriolar pressure during occlusion of the superior venae cavae. Thus, similar increases in venous pressure during acute hypertension and superior venae cavae occlusion, despite directionally opposite changes in arterial and arteriolar pressure, produced similar disruption of the blood-brain barrier.(ABSTRACT TRUNCATED AT 250 WORDS)

Role of proximal convoluted tubule in pressure diuresis in the rat.

The role of different nephron segments in the diuretic response to acute arterial hypertension was studied with tubular microperfusion. Early proximal convolutes were perfused with synthetic glomerular ultrafiltrate; fluid was collected from the last visible loop of the same proximal or from the first loop of the distal tubule. In late proximal collections, an increase of arterial pressure of 24 +/- 2 mmHg reduced reabsorption of tubular fluid 44 +/- 4%. Perfusate chloride concentration fell, but only 2 meq/liter, so that chloride reabsorption was inhibited in proportion to the inhibition of fluid reabsorptions, with a corresponding increase in chloride delivery to the loop of Henle. In early distal collections, there was no significant difference of the early distal flow rate with hypertension, but early distal chloride concentration increased 31 +/- 8% and chloride load increased 45 +/- 12%. Qualitatively similar increases were obtained from paired collections made from free-flowing early distal tubules. Inhibition of proximal fluid reabsorption is a primary response to acute hypertension and may contribute to pressure diuresis. In addition, this inhibition increases the strength of the luminal signal to the macula densa, enhancing the autoregulatory response to hypertension.

Focal brain edema associated with acute arterial hypertension.

Acute arterial hypertension was studied in normal cats to determine its role in the formation of brain edema. Arterial hypertension was induced for 30 minutes by inflation of a balloon catheter situated in the descending aorta. Cerebral edema was evaluated by gross and microscopic observations, tissue water content by wet/dry weights, and blood-brain barrier (BBB) permeability by extravasation of horseradish peroxidase (HRP) and Evans blue dye. For 1 hour after the hypertensive insult, tissue pressure and regional cerebral blood flow (rCBF) were measured from the arterial boundary zone and from a non-boundary region, and intracranial pressure was recorded from the lateral ventricle as ventricular fluid pressure. Focal lesions with increased BBB permeability to Evans blue dye or HRP were usually located symmetrically in the cortex, corresponding to the occipitoparietal parts of the arterial boundary zones. The increase in water content was found only in areas of increased permeability. Tissue pressure increased simultaneously with the abrupt rise in blood pressure, and an increase in rCBF paralleled the elevation of blood pressure. Tissue pressure and rCBF returned to a steady state when blood pressure returned to normal. There were no differences in tissue pressure or rCBF between the arterial boundary zone and the non-boundary zone, even during arterial hypertension. In cerebral hemispheres examined 48 hours after the hypertensive challenge, brain edema had not continued to develop. The data indicate that acute arterial hypertension may produce focal brain edema with increased permeability of the BBB in the cortex of normal brain, particularly in the arterial boundary zones. The authors postulate that increased cerebral blood volume, high intraluminal pressure, and breakthrough of autoregulation play an important role in the formation of hypertensive brain edema.

Oxygen radicals in the adult respiratory distress syndrome, in myocardial ischemia and reperfusion injury, and in cerebral vascular damage.

Recent work suggests that oxygen radicals may be important mediators of damage in a wide variety of pathologic conditions. In this review we consider the evidence supporting the participation of oxygen radicals in the adult respiratory distress syndrome, in ischemia reperfusion injury in the myocardium, and in cerebral vascular injury in acute hypertension and traumatic brain injury. In the adult respiratory distress syndrome there is active sequestration of polymorphonuclear neutrophils in the pulmonary vascular system. There is evidence that activation of these neutrophils results in the production of oxygen radicals which injure the capillary membrane and increase permeability, leading to progressive hypoxia and decreased lung compliance which are hallmarks of the syndrome. In acute arterial hypertension or experimental brain injury oxygen radicals are important mediators of vascular damage. The metabolism of arachidonic acid is the source of oxygen free radical production in these conditions. In myocardial ischemia and reperfusion injury, the ischemic myocyte is "primed" for free radical production. With reperfusion and reintroduction of molecular oxygen there is a burst of oxygen radical production resulting in extensive tissue destruction. Myocardial ischemia--reperfusion injury shares in common with the other two syndromes activation of the arachidonic acid cascade and acute inflammation. Thus it would appear that the generation of toxic oxygen species may represent a final common pathway of tissue destruction in several pathophysiologic states.

Stereologic analysis of structures of the parenchyma and stroma of hypertrophied myocardium in acute arterial hypertension

It has been shown in experiments on Wistar male rats with the use of light and electron microscopy and morphometry that a single intraperitoneal injection of high doses of all-trans-methylretinoate and methyl-7,8- dihydroretinoate leads to an increase in the spleen weight, the appearance in the spleen of red cells changed in the shape, activation of phagocytic intensity of macrophages, intercellular interaction, lymphocyte proliferation and formation of new lymph follicles.

Calcium antagonists: effects on cerebral blood flow and blood‐brain barrier permeability in the rat

1 Because they affect isolated cerebral arteries, some calcium antagonists have been studied on the intact cerebral circulation of the rat.2 Global cerebral blood flow ((133)Xe clearance technique) was measured in anaesthetized rats. Neither perhexiline (0.1 mug/kg to 1.0 mg/kg, i.v.) nor diltiazem (0.06-0.6 mg/kg, i.v.) had any significant effect on resting cerebral blood flow when measured 5 min after each dose. A high dose of nifedipine (1.0 mg/kg, i.v.) was administered during induced hypocapnia. Nifedipine failed to modify the hypocapnic vasoconstriction of the cerebral vasculature when compared to vehicle-treated rats.3 The possibility of discrete changes in regional cerebral blood flow was investigated. Local cerebral blood flow was measured in a number of brain regions by the [(14)C]-ethanol technique 15 min after the administration of nifedipine (20 or 100 mug/kg, i.v.). Nifedipine had no apparent effect on regional blood flow in the rat brain.4 Acute arterial hypertension increases protein leakage into the brain, a phenomenon susceptible to drugs that act on endothelial pinocytosis which is known to be calcium-dependent. The increase in protein extravasation, induced by the intravenous administration of either angiotensin II or adrenaline, was unchanged in rats previously treated with either nimodipine (20 mug/kg, i.v.) or nifedipine (50 mug/kg, i.v.) when dissolved in ethanol alone. However, nifedipine (20 mug/kg, i.v.) when dissolved in a solution of polyethylene glycol and ethanol further enhanced the hypertension-induced increase in brain albumin permeability.5 In conclusion, we have been unable to demonstrate any apparent effects of various calcium antagonists on the intact cerebral circulation of the rat, despite the number of different experimental models used.

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.

Sympathetic effects on cerebral and ocular blood flow in rabbits pretreated with indomethacin.

The effects of unilateral stimulation of the cervical sympathetic chain on cerebral and ocular blood flow was investigated in 8 rabbits anesthetized with pentobarbital sodium and pretreated with indomethacin in order to inhibit the formation of prostaglandins. Blood flow determinations were made with the labelled microsphere method during normotension and acute arterial hypertension. Hypertension was induced by ligation of the thoracic aorta. Evans blue was given as a tracer for protein leakage during hypertension. Sympathetic stimulation had no significant effect on the blood flow in the brain under the two conditions studied. In the uvea marked effects of sympathetic stimulation were obtained at normotension as well as at hypertension. There were no indications of breakdown of the blood-brain barrier or the blood-aqueous barrier. Thus, there was no evidence for any prostaglandin-mediated inhibition of sympathetic effects in the brain or the eye.

Effects of sympathetic stimulation on cerebral and ocular blood flow. Modification by hypertension, hypercapnia, acetazolamide, PGI2 and papaverine.

The effect of unilateral, electrical stimulation of the cervical sympathetic chain in rabbits anesthetized with pentobarbital sodium and vasodilated by hypercapnia, acetazolamide, papaverine or PGI2 was investigated to determine to what extent the sympathetic nerves to the brain and the eye cause vasoconstriction and prevent overperfusion in previously vasodilated animals. Evans blue was given as a tracer for protein leakage. Blood flow determinations were made with the labelled microsphere method during normotension and acute arterial hypertension. Hypertension was induced by ligation of the thoracic aorta and in some animals metaraminol or angiotensin was also used. Acetazolamide caused a two to threefold increase in cerebral blood flow (CBF) and hypercapnia resulted in a fivefold increase. CBF was not markedly affected by papaverine or PGI2. In the choroid plexus, the ciliary body and choroid, papaverine and hypercapnia caused significant blood flow increases on the control side. Sympathetic stimulation induced a 12% blood flow reduction in the brain in normotensive, hypercapnic animals. Marked effects of sympathetic stimulation at normotension were obtained under all conditions in the eye. In the hypertensive state the CBF reduction during sympathetic stimulation was moderate, but highly significant in hypercapnic or papaverine-treated animals as well as in controls. Leakage of Evans blue was more frequently seen on the nonstimulated side of the brain. In the eye there was leakage only on the control side except in PGI2-treated animals where 2 rabbits had bilateral leakage. The effect of sympathetic stimulation on the blood flow in the cerebrum and cerebellum in vasodilated animals seems to be small or absent if the blood pressure is normal. In the eye pronounced vasoconstriction occurs under these conditions. In acute arterial hypertension sympathetic stimulation protects both the cerebral and ocular barriers even under conditions of marked vasodilation.

Acute arterial hypertension during spontaneous angina in patients with fixed coronary stenosis and exertional angina: an associated rather than a triggering phenomenon.

The role of systemic arterial hypertension as a possible trigger of myocardial ischemia during angina at rest was studied in 13 consecutive patients who also had a history of exertional angina. Significant (greater than or equal to 70%) stenosis of at least one major vessel was present in each of the 10 patients in whom coronary arteriography was carried out. After documentation of the electrocardiographic and arterial blood pressure changes during two or more episodes of resting angina, i.v. methoxamine was infused under continuous monitoring of the ECG, arterial blood pressure and pulmonary artery diastolic pressure. The heart rate was maintained either spontaneously or by atrial pacing to levels similar to those during angina at rest. Despite increases in arterial blood pressure and the double product (systolic blood pressure x heart rate) to levels higher than those during spontaneous angina in all patients, no chest pain or electrocardiographic changes occurred in nine patients. In the other four patients, however, angina supervened. Three of these four patients, but only one of the remaining nine, had a borderline or elevated pulmonary artery diastolic pressure at rest. We conclude that in a considerable number of patients with "nonvariant" resting angina, acute increases in arterial blood pressure during the spontaneous attacks are not likely to be the cause of myocardial ischemia. Nevertheless, in some of these patients, increases in resting pulmonary artery diastolic pressure may favor the development of ischemia during afterload augmentation.

Cerebral circulation in acute arterial hypertension—protective effects of sympathetic nervous activity

The cervical sympathetic chain was stimulated electrically at 6 or 3 Hz on one side in anesthetized cats. Acute arterial hypertension was induced by ligation of the aorta. Evans blue was given as tracer for protein leakage. The regional blood flow in the brain was determined by using labelled microspheres. At high blood pressures there was a multifocal breakdown of the blood-brain barrier. The regions with breakdown had 10-20 times the normal flow rates. With a maintained hypertension regions which were overperfused at 5 min were still overperfused at 10 min, but there was little addition of new overperfused areas. Normalization of the pressure resulted in almost twice the normal flow rates in previously overperfused regions. The breakdown of the blood-brain barrier was restricted to the non-stimulated side, or more marked on that side. The protective effect of the sympathetic stimulation lasted more than 10 min. The results indicate that acute arterial hypertension tends to cause forced and long-lasting vasodilation in some areas in the brain but regions which are resistant to the acute rise have an increase in the vascular tone. Sympathetic activity helps in developing this tone. Normalization of the blood pressure results in partial recovery of the vascular tone in previously overperfused regions and normalization in other areas.

Cerebral venous pressure during actively induced hypertension and hypercapnia in cats.

Superior sagittal sinus pressure, intracranial pressure and arterial pressure were recorded in an experimental series on 10 cats. During drug-induced, severe, acute arterial hypertension and parallel hypercapnia, venous pressure could exceed intracranial pressure in both the supra- and infratentorial compartment. From these data it is concluded that cerebral venous pressure during acute arterial hypertension may contribute to protein extravasation at the postcapillary-venular level.

The blood-brain barrier in acute and chronic hypertension.

Acute arterial hypertension, induced by vasoactive substances or by compression of the thoracic aorta, can increase the permeability of the blood-brain barrier (BBB) in experimental animals (1). The present review deals predominantly with the BBB to macromolecules, since that is the BBB function most commonly studied in experimental hypertension. The abnormal permeability associated with hypertension has a typical, patchy appearance, although the pattern varies somewhat with different experimental models (see below and 1–6). This BBB dysfunction, which is rapidly reversible when the pressure returns to normal levels (7), is a direct consequence of the increased mechanical stress on the endothelial cells caused by the high intravascular pressure (1). An early hypothesis stating that the increased permeability was due to ischemia has been refuted for the following reasons: 1) the increased permeability to macromolecules is evident within seconds after the pressure increase, while it takes much longer for ischemia to cause this change in the BBB (1); 2) the cerebral blood flow is higher in areas with disturbed permeability than in surrounding tissue (8,9); and 3) energy metabolism in the brain is not disturbed in shortlasting acute hypertension (10,11).KeywordsCerebral Blood FlowBrain EdemaChronic HypertensionHypertensive EncephalopathyRenal HypertensionThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Opening of tight junctions in cerebral endothelium. II. Effect of pressure‐pulse induced acute arterial hypertension

Acute arterial hypertension was produced in male Wistar rats by pressure pulse through the right internal carotid artery. The pressure pulse was induced by infusion of physiological saline as a bolus, at a rate of 0.63 ml per second by syringe pump. Evans blue (Eb) was used to visualize the areas of blood-brain barrier opening. Intravenously injected horseradish peroxidase (HRP) was used to study the ultrastructural basis of permeability changes in cerebral endothelium. Eb outlined circumscribed areas of blood-brain barrier opening. HRP extravasation was found mainly around small arteries. The capillary network was affected to a much lesser extent. Electron microscopy showed that HRP crossed the endothelial cell layer by intercellular routes. Glutaraldehyde fixed brain samples permeated with colloidal lanthanum supported these observations.