Induced Increases In Blood Pressure Research Articles

The Hyperintense study: Assessing the effects of induced blood pressure increase and decrease on MRI markers of cerebral small vessel disease: Study rationale and protocol.

Background:Neuroimaging markers of cerebral small vessel disease (SVD) are common in older individuals, but the pathophysiological mechanisms causing these lesions remain poorly understood. Although hypertension is a major risk factor for SVD, the direct causal effects of increased blood pressure are unknown. The Hyperintense study is designed to examine cerebrovascular and structural abnormalities, possibly preceding SVD, in young adults with hypertension. These patients undergo a diagnostic work-up that requires patients to temporarily discontinue their antihypertensive agents, often leading to an increase in blood pressure followed by a decrease once effective medication is restarted. This allows examination of the effects of blood pressure increase and decrease on the cerebral small vessels.Methods:Hyperintense is a prospective observational cohort study in 50 hypertensive adults (18–55 years) who will temporarily discontinue antihypertensive medication for diagnostic purposes. MRI and clinical data is collected at four timepoints: before medication withdrawal (baseline), once antihypertensives are largely or completely withdrawn (T = 1), when patients have restarted medication (T = 2) and reached target blood pressure and 1 year later (T = 3). The 3T MRI protocol includes conventional structural sequences and advanced techniques to assess various aspects of microvascular integrity, including blood-brain barrier function using Dynamic Contrast Enhanced MRI, white matter integrity, and microperfusion. Clinical assessments include motor and cognitive examinations and blood sampling.Discussion:The Hyperintense study will improve the understanding of the pathophysiological mechanisms following hypertension that may cause SVD. This knowledge can ultimately help to identify new targets for treatment of SVD, aimed at prevention or limiting disease progression.

Effects of Estrogen on Water Intake, Urine Volume, Sodium Excretion, and Blood Pressure During a Ten‐Day Angiotensin II Infusion Period in Ovariectomized Mice

Sex steroids play important roles in blood pressure regulation as well as in other physiological regulatory systems. Although estrogen replacement is thought to prevent or reduce cardiovascular disease in postmenopausal women, conflicting evidence exists as to whether or not estrogen reduces blood pressure. The main purpose of this study was to determine if estrogen administration reduces angiotensin II (Ang II)‐induced increase in blood pressure in ovariectomized (OVX) mice. Four‐week‐old CD‐1 OVX mice were purchased from Envigo Inc. (Indianapolis, IN) and placed in metabolic cages for a five‐day baseline period followed by implantation of an Alzet osmotic pump containing either vehicle or Ang II (1μg/kg/min) and either a placebo or 0.7 mg b‐estradiol (E2) pellet (Innovative Research of America, Sarasota, FL). Measurements were recorded daily in the five‐day baseline and ten‐day post‐implantation periods in three groups of mice: vehicle‐placebo (V‐P), Ang II‐placebo (Ang II‐P), and Ang II‐estrogen (Ang II‐E2) (n=4/group). Mice consumed standard chow and tap water ad libitum throughout the study. Systolic blood pressure (SBP, mmHg) was determined daily via the tail‐cuff technique (CODA, Kent Scientific, Torrington, CT). The delta SBP (baseline vs Ang II periods) was higher in Ang II‐P mice but not significantly different from the Ang II‐E2 mice: (33.1 ± 3.5 vs 24.5 ± 4.0, respectively). Additionally, these values were not significantly different from the delta SBP (30.5 ± 6.1) from intact female (IF) CD‐1 mice under the same Ang II conditions determined in a previous study (Rouch, A. el al. FASEB J, 2018, A 904.6). Using repeated‐measures ANOVA, we found significant effects of E2 on water intake (WI), urine volume (UV), and sodium excretion (UNaE) during the 10‐day post‐implantation period (no differences occurred in the baseline period). E2 appeared to prevent an Ang II‐induced increase in water WI (ml/day): (Ang II‐P vs AngII‐E2; 6.9 ± 0.5 vs 4.2 ± 0.2, p < 0.001). E2 administration resulted in lower UV (ml/day): (Ang II‐P vs Ang II‐E2; 2.6 ± 0.3 vs 1.3 ± 0.2, p<0.03). E2 administration also resulted in lower UNaE (microEq/day): (Ang II‐P vs Ang II‐E2, 199.7 ± 10.8 vs 110.5 ± 20.7, p < 0.003). We conclude that continuous E2 administration via the 0.7 mg E2 pellet affects WI, UV, and UNaE during a ten‐day Ang II infusion period in OVX CD‐1 mice. Moreover, neither the pellet‐induced E2 administration nor endogenous estrogen in IF mice affected the Ang II‐induced increase in blood pressure. Studies of longer duration with more mice/group are underway to investigate mechanistic differences due to E2.Support or Funding InformationThis project was supported by the National Institute of General Medical Sciences of National Institutes of Health through Grant Number 8P20GM103447.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

OS 25-04 THE CHANGES OF ARTERIAL STIFFNESS MONITORED WITH CARDIO ANKLE VASCULAR INDEX (CAVI) DURING RAISED INTRACRANIAL PRESSURE IN THE RABBIT

Objective: Cardio ankle vascular index (CAVI) is reflecting stiffness of the arterial tree from the origin of aorta to the ankles. We observed elevated CAVI in patients who suffered from apoplexy attack. To clarify the role and the mechanism by which arterial stiffness elevated just after apoplexy attack, the effect of enhanced intracranial pressure (ICP) by injecting saline into the cisterna magna of the rabbit on blood pressure, CAVI and cervical blood flow, were studied. Furthermore the role of sympathetic nerve was studied. Design and Method: The system of measuring CAVI of the New Zealand white rabbit was set up. General anesthesia was performed by ketamine and xylazine, and the respirator was set. Intracranial pressure (ICP) was monitored using a catheter inserted into subarachnoid space via right frontal bone craniotomy. Saline (15 ml) was inserted to raise ICP. Ganglion blocker, hexamethonium (10 μg/kg/10 min, and 100 μg/kg/10min) was administered just before saline injection. Results: When saline was injected into the cisterna magna and ICP was raised over 20 mmHg at least, blood pressure (62 ± 7.43 → 135 ± 27.41 mmHg), and CAVI (3.3 ± 0.39 → 4.8 ± 0.89) were increased. The heart rate and blood flow of common carotid artery increased. When hexamethonium (10 μg/kg/10 min and 100 μg/kg/10min) was administered before raising ICP, enhanced IPP -induced blood pressure increase (123 ± 9.58, 90 ± 5.42 mmHg, respectively) and CAVI increase (4.3 ± 0.35, 4.0 ± 0.16, respectively) were inhibited dose-dependently. Conclusions: Raised ICP induced an increase of blood pressure accompanying with an increase of CAVI, suggesting that enhanced stiffness of muscle artery might partly induce high blood pressure. Blocking sympathetic nerve by hexamethonium diminished raised blood pressure and CAVI, indicating that ICP increase-induced blood pressure and CAVI increases were mediated by sympathetic nerve activation.

Persistent Increase in Blood Pressure After Renal Nerve Stimulation in Accessory Renal Arteries After Sympathetic Renal Denervation

Blood pressure response to renal denervation is highly variable, and the proportion of responders is disappointing. This may be partly because of accessory renal arteries too small for denervation, causing incomplete ablation. Renal nerve stimulation before and after renal denervation is a promising approach to assess completeness of renal denervation and may predict blood pressure response to renal denervation. The objective of the current study was to assess renal nerve stimulation-induced blood pressure increase before and after renal sympathetic denervation in main and accessory renal arteries of anaesthetized patients with drug-resistant hypertension. The study included 21 patients. Nine patients had at least 1 accessory renal artery in which renal denervation was not feasible. Renal nerve stimulation was performed in the main arteries of all patients and in accessory renal arteries of 6 of 9 patients with accessory arteries, both before and after renal sympathetic denervation. Renal nerve stimulation before renal denervation elicited a substantial increase in systolic blood pressure, both in main (25.6±2.9 mm Hg; P<0.001) and accessory (24.3±7.4 mm Hg; P=0.047) renal arteries. After renal denervation, renal nerve stimulation-induced systolic blood pressure increase was blunted in the main renal arteries (Δ systolic blood pressure, 8.6±3.7 mm Hg; P=0.020), but not in the nondenervated renal accessory renal arteries (Δ systolic blood pressure, 27.1±7.6 mm Hg; P=0.917). This residual source of renal sympathetic tone may result in persistent hypertension after ablation and partly account for the large response variability.

Aging, arterial stiffness, and hypertension.

Although the etiology of essential hypertension remains unknown, it is clear that multiple factors may contribute to the pathogenesis of hypertension. Hypertension is an outcome of the interaction of multiple genetic and environmental factors. Several epidemiological studies indicated that the incidence of arterial stiffness and hypertension and related cardiovascular disease (stroke, myocardial infarction) is higher in the aged than in the young population.1–4 The prevalence of arterial stiffening and hypertension increases with age.1,5 Based on an epidemiological study,6 the prevalence of hypertension is more than doubled in the elderly than in the young population. More than two-thirds of individuals after 65 years of age experience hypertension according to the Seventh Report of the Joint National Committee (JNC-7).7 Therefore, it is generally thought that hypertension is an aging disorder. In recent years, metabolic syndrome and hypertension are increasingly seen in the middle-aged and young populations. In these subpopulations, insulin resistance and overproduction of adipokines impair endothelial and heart function leading to early and accelerated cardiovascular aging. It was reported that premature aging (progeria) is associated with accelerated vascular stiffening or vascular aging.8 Aging is defined as the age-related decline in physiological function essential for survival and fertility. Cardiovascular aging is an important factor that determines life span. The wall of large conduit arteries, especially aorta, thicken and lose elasticity over time, and this process results in an increase in pulse wave velocity, an important and reliable measure of arterial stiffness. The increased arterial stiffness, whatever its underlying causes, would reduce the reservoir/buffering function of the conduit arteries near the heart and increase pulse wave velocity, both of which increase systolic and pulse pressure. Therefore, aging-related hypertension is characterized by a significant increase in systolic blood pressure with no change or even a …

Microglia, a new cellular factor, in the development of hypertension (875.6)

The concept of neuroinflammation in the development of hypertension has been acknowledged recently, as studies showed that anti‐inflammation treatments attenuated Ang II induced blood pressure increase. Microglia are the major immune cells in the central nervous system. To examine the role of microglia in hypertension, we applied a microglial depletion strategy by using a transgenic mouse line CD11b‐DTR. This mouse line has an inserted transgene coding simian diphtheria toxin receptor (DTR) under the control of the CD11b promoter. CD11b‐DTR mice were made hypertensive by subcutaneous Ang II infusion. Two weeks later, the mice received intracerebroventricular infusion of either DT or saline. Blood pressure was monitored by tailcuff. It showed that systolic blood pressure reached ~140 mmHg in both groups by 2 wk. Microglial depletion caused a gradual reduction in blood pressure (20 mmHg) by the end of 4 wk. To validate the importance of microglia in neuroinflammation associated with hypertension, the expression of pro‐inflammatory cytokines in paraventricular nucleus (PVN) were analyzed by quantative RT‐PCR. Microglial depletion reduced the expression of both IL‐1β and TNFα in the PVN of hypertensive mice. Moreover, the norepinephrine levels in the kidney were significantly decreased in the microglia‐depleted mice vs. controls. These data strongly support our hypothesis that in hypertension, microglia play an importance role in initiating neuroinflammation and in sustaining blood pressure.Grant Funding Source: AHA and UCLA CTSI

Grape Seed Proanthocyanidin Extracts Enhance Endothelial Nitric Oxide Synthase Expression through 5′-AMP Activated Protein Kinase/Surtuin 1–Krüpple Like Factor 2 Pathway and Modulate Blood Pressure in Ouabain Induced Hypertensive Rats

Grape seed proanthocyanidin extracts (GSPE) belonging to polyphenols, possess various biological effects including anti-inflammation, anti-oxidant, anti-aging, anti-atherosclerosis, etc. GSPE is potential in regulating endothelial function. However, the underlying mechanism is not clear yet. In this study, by small interfering RNA (siRNA) knocking down, we proved that GSPE increase endothelial nitric oxide synthase (eNOS) expression in human umbilical vessel cells (HUVECs) in vitro, which was attributed to its transcription factor Krüpple like factor 2 (KLF2) induction. Furthermore, GSPE activate 5'-AMP activated protein kinase (AMPK) and increase surtuin 1 (SIRT1) protein level, critical for KLF2 induction. We also illuminated the role of GSPE in hypertension treatment. By chronic administration of GSPE in ouabain induced hypertensive rats model, we access the effect of GSPE on blood pressure regulation and the possible mechanisms involved. After 5 weeks feeding, GSPE significantly block the ouabain induced blood pressure increase. The aortic NO production impaired by ouabain was improved. In conclusion, GSPE increase eNOS expression and NO production in an AMPK/SIRT1 dependent manner through KLF2 induction, and attenuate ouabain induced hypertension.

Silencing of Hypoxia-Inducible Factor-1α Gene Attenuated Angiotensin II–Induced Renal Injury in Sprague-Dawley Rats

Although it has been shown that upregulation of hypoxia-inducible factor (HIF)-1α is protective in acute ischemic renal injury, long-term overactivation of HIF-1α is implicated to be injurious in chronic kidney diseases. Angiotensin II (Ang II) is a well-known pathogenic factor producing chronic renal injury and has also been shown to increase HIF-1α. However, the contribution of HIF-1α to Ang II-induced renal injury has not been evidenced. The present study tested the hypothesis that HIF-1α mediates Ang II-induced renal injury in Sprague-Dawley rats. Chronic renal injury was induced by Ang II infusion (200 ng/kg per minute) for 2 weeks in uninephrectomized rats. Transfection of vectors expressing HIF-1α small hairpin RNA into the kidneys knocked down HIF-1α gene expression by 70%, blocked Ang II-induced HIF-1α activation, and significantly attenuated Ang II-induced albuminuria, which was accompanied by inhibition of Ang II-induced vascular endothelial growth factor, a known glomerular permeability factor, in glomeruli. HIF-1α small hairpin RNA also significantly improved the glomerular morphological damage induced by Ang II. Furthermore, HIF-1α small hairpin RNA blocked Ang II-induced upregulation of collagen and α-smooth muscle actin in tubulointerstitial region. There was no difference in creatinine clearance and Ang II-induced increase in blood pressure. HIF-1α small hairpin RNA had no effect on Ang II-induced reduction in renal blood flow and hypoxia in the kidneys. These data suggested that overactivation of HIF-1α-mediated gene regulation in the kidney is a pathogenic pathway mediating Ang II-induced chronic renal injuries, and normalization of overactivated HIF-1α may be used as a treatment strategy for chronic kidney damages associated with excessive Ang II.

Testosterone Increases: Sodium Reabsorption, Blood Pressure, and Renal Pathology in Female Spontaneously Hypertensive Rats on a High Sodium Diet

Estrogen (E) and testosterone (T) are important in the sexually dimorphic pattern of blood pressure (BP) development. The goal was to examine the effects of endogenous E and exogenous T in the development of hypertension in female spontaneously hypertensive rats (SHR) on a high sodium diet. Female SHR (N = 27, 5-week) were divided into four groups: (1) control (n = 8), (2) ovariectomized (OVX, n = 26), (3) testosterone implants with intact ovaries (T, n = 6), and (4) ovariectomized + testosterone implants (OVX+T, n = 7). T was given immediately after OVX and replaced every two weeks and they were fed a 3% NaCl diet. BP was measured weekly and plasma norepinephrine (NE) analyzed by HPLC. OVX+T females exhibited the greatest elevation in BP (190 ± 4.0 mmHg) compared to controls at 15 weeks of age (140 ± 3.4 mmHg, P < .001) and a pattern of hypertension development similar to that of male SHR. Females with T treatment showed evidence of glomerulosclerosis. In conclusion, T accelerated the development of hypertension similar to the BP pattern observed in males; the presence of ovaries attenuated the T induced increase in BP; T increased renal sodium reabsorption, and T increased glomerulosclerosis.

Coffee Blunts Mental Stress–Induced Blood Pressure Increase in Habitual but Not in Nonhabitual Coffee Drinkers

Coffee is widely consumed, especially during mental stress conditions. Cardiovascular impact of coffee remains debated because the underlying mechanisms of action are complex. We reported previously differential cardiovascular stimulation of coffee at rest depending on habitual consumption. The present study was designed to evaluate the effects of coffee on cardiovascular response to mental stress. In 15 healthy volunteers (6 habitual, 9 nonhabitual coffee drinkers), we assessed the effect of mental stress on blood pressure (BP), heart rate (HR), and muscle sympathetic activity (MSA) before and after a triple espresso, intravenous caffeine, and placebo in the same subjects. Under baseline conditions, mental stress significantly increases MSA (+2.5+/-0.7 volts per minute; +14.1+/-10.3%), systolic (+11.6+/-4.1 mm Hg) and diastolic BP (+6.4+/-2.0 mm Hg), and HR (+9.6+/-1.8 minutes(-1)). In nonhabitual coffee drinkers, a triple espresso but not caffeine induced an additional increase in systolic BP (+9+/-6.3 mm Hg; P=0.003) during mental stress, whereas in habitual drinkers, the stress-induced BP increase was blunted (+4+/-3.9 mm Hg; P=NS). As a result, nonhabitual coffee drinkers experienced significantly higher BP during mental stress than habitual drinkers (151+/-17.9/83+/-5.6 mm Hg versus 130+/-7.8/74+/-6.7 mm Hg; P<0.05). Caffeine induced similar effects in habitual and nonhabitual coffee drinkers at rest and during mental stress. The response to the cold pressor test was not influenced by coffee drinking in both groups. In conclusion, in nonhabitual coffee drinkers, coffee enhances the cardiovascular response to mental stress with an additional increase in systolic BP, whereas in habitual drinkers, the response is blunted. Caffeine alone does not exert any potentiating effect, confirming that ingredients other than caffeine are partially responsible for the stimulating effect of coffee on the cardiovascular system.

Lead induced increase of blood pressure in female lead workers

Aims: Although lead exposure has, in the absence of mathematical modelling, been believed to elevate blood pressure in females, it is necessary to clarify the relation between lead and blood...

Arterial baroreflex modulation of heart rate in patients early after heart transplantation: lack of parasympathetic reinnervation

Background: Orthotopic heart transplantation results in cardiac denervation. The presence of cardiac parasympathetic reinnervation in humans has been widely debated based on the application of differing indirect measures of autonomic control. However no attempt has been made to analyse the reflex heart rate response to baroreceptor stimulation whose occurrence is generally considered a reliable marker of the ability to activate cardiac vagal reflexes. This study tested the hypothesis that the presence of donor heart RR interval lengthening following phenylephrine induced blood pressure increase would be an index of parasympathetic reinnervation. Methods Baroreflex sensitivity (BRS) was assessed in 30 patients (mean age 51 ± 12 years) 1–24 months after heart transplantation carried out by the standard Lower-Shumway technique. In 6 patients the recipient atrium rate response (P-P interval) to baroreceptor stimulation by phenylephrine was also simultaneously determined by transesophageal recording. Results None of the 30 patients showed prolongation of RR intervals in the donor heart. The average BRS value was −0.28 ± 0.54 ms/mmHg (range −1.3–0.7 ms/mmHg). In the 6 patients in whom BRS was obtained at both the recipient atrium (P-P) and donor heart (R-R) the changes were 7.6 ± 5.7 ms/mmHg and −0.38 ± 0.58 ms/mmHg respectively ( p = 0.02), thus confirming that the absent RR interval lengthening in the donor heart is the consequence of efferent vagal fiber interruption. Conclusions The absence of any RR interval prolongation following phenylephrine induced baroreceptor stimulation demonstrates that vagal efferent reinnervation of the donor heart does not occur up to 24 months in patients operated via the standard Lower-Shumway procedure. It is also suggested that analysis of baroreceptor reflexes is a more specific method in the examination of cardiac parasympathetic reinnervation.

Synthesis and biological activity of ketomethylene-containing nonapeptide analogues of snake venom angiotensin converting enzyme inhibitors.

Two ketomethylene-containing nonapeptide analogues were synthesized to determine if ketomethylene analogues of the nonapeptide venom inhibitors of angiotensin converting enzyme (ACE) would have oral ACE inhibition activity. Both ketomethylene-containing nonapeptides 18 and 19 were potent inhibitors of rabbit lung ACE with I50s of 3.4 and 8.0 nM, respectively, compared to 340 nM for their parent nonapeptide and 450 nM for captopril. Peptide 18 was rapidly cleaved by trypsin, but 19 was reasonably stable to all enzyme degradation systems tested with maximum degradation of 50% by pepsin in 3 h. Both 18 and 19 when given iv to normotensive rats were between 3 and 10 times more potent than captopril in inhibiting an angiotensin I induced blood pressure increase. Peptide 19 showed no ACE inhibition activity in unanesthetized normotensive rats when administered orally at doses of 10 or 100 mg/kg. Experiments were conducted to determine whether 19 is adsorbed from the gastrointestinal track following oral administration. These experiments indicated that 19 is adsorbed. It is concluded that the lack of oral activity of 19 is probably due to its rapid excretion, probably into the bile.

The influence of orphenadrine or imipramine on the hypertensive response of physostigmine in the rat.

An intravenous infusion of orphenadrine or imipramine to artificially ventilated, urethane anaesthetized rats, completely blocked the physostigmine induced increase in blood pressure and the blood pressure increase induced by electrical stimulation of the posterior hypothalamus; effects mediated via the sympathetic nerve. The noradrenaline induced blood pressure increase was not changed during an infusion with orphenadrine but was markedly depressed during an infusion with imipramine. During an infusion with both orphenadrine or imipramine the pressor response induced by stimulation of the spinal cord were completely blocked in pithed rats. The pattern of the blockade was comparable with the blockade of the pressor response after hypothalamic stimulation. These results show that at least in rats both orphenadrine and imipramine prevents the central stimulatory sympathetic effects on the cardiovascular system by interfering with the sympathetic nervous system. The site of action is discussed. the present results show that although physostigmine may be helpful in the treatment of central anticholinergic effects caused by overdoses of orphenadrine and imipramine it is of no use for combating the direct toxic effects of both drugs on the cardiovascular system.

Derivatives of the potent angiotensin converting enzyme inhibitor 5(S)-benzamido-4-oxo-6-phenylhexanoyl-L-proline: effect of changes at positions 2 and 5 of the hexanoic acid portion.

Several derivatives of the potent angiotensin converting enzyme inhibitor 5(S)-benzamido-4-oxo-6-phenylhexanoyl-L-proline (1) were synthesized and tested for converting enzyme inhibition activity and blood pressure lowering effects in rats. One compound, 5(S)-benzamido-2(R)-methyl-4-oxo-6-phenylhexanoyl-L-proline (2a), had and I50 against angiotensin converting enzyme of 1.0 x 10(-9) M and is the most potent inhibitor prepared thus far in this class of compounds. Testing of 2a orally at 30 mg/kg for inhibition of the angiotensin I induced blood pressure increase in conscious normotensive rats gave 100% inhibition that required 143 min before the angiotensin I blood pressure response returned to 70% of the pretreatment control response. In the conscious renal hypertensive rat, 2a given orally at a dose of 3 mg/kg caused a lowering of blood pressure that reached its maximum of 40 mmHg 8 h following drug administration.

Mechanism of blood pressure reduction by teprotide (SQ 20881) in rats

The mechanism by which the angiotensin converting enzyme inhibitor, teprotide (SQ 20881), lowers blood pressure was assessed in anesthetized normotensive and spontaneously hypertensive (SHR) rats. Teprotide always was administered at a maximally effective dose of 1 mg/kg. In six normal Wistar rats, teprotide lowered blood pressure only after sodium depletion, an effect which was abolished by bilateral nephrectomy. Saralasin infusion (5 microgram/kg/min) into salt-depleted normal rats induced a blood pressure effect similar to that of teprotide. When administered in addition to saralasin infusion, teprotide did not reduce blood pressure further in normal rats or in SHR. When blood pressure of normal rats was raised by angiotensin II infusion (200 ng/kg/min), teprotide did not affect the induced blood pressure increase. In contrast, the pressure rise induced by angiotensin I infusion (230 ng/kg/min) was reversed by saralasin, but again concomitant administration of teprotide did not induce further blood pressure reduction. Thus, under the particular conditions of the present study, teprotide did not appear to exert its hypotensive effect by any mechanism other than inhibition of the renin-angiotensin system. Furthermore, given at a maximally effective dose to the rat, it produced no greater vasodepressor effect than did saralasin.

The sausage-string phenomenon in acutely induced hypertension--arguments against the vasospasm theory in the pathogenesis of acute hypertensive encephalopathy.

Pial microcirculation was observed in cats during acutely induced blood pressure increase using the window technique. Measurements of arteriolar diameter changes in situations of preserved and altered cerebrovascular autoregulation were made, when diffuse vasoconstriction and sausage-like dilation, respectively, occurred. Comparison of percentage changes of narrow segments between sausage-like dilated arterioles and diffusely constricted (= autoregulating) vessels gave evidence that a failure of autoregulation in this situation is not associated with vasospasm but with dilation. Individual narrow segments did not constrict more--but on an average even rather less--than diffusely constricted vessels. Evans blue extravasation occurred only with dilation, never with vascular constriction. From these data it is concluded that extravasation due to acute blood pressure increase is not of ischemic nature, but a consequence of high filtration pressure due to arteriolar and venous congestion.

Inhibition of adrenal secretion of epinephrine during infusion of catecholamines.

The effect of intravenous infusion of epinephrine or norepinephrine on the secretion of epinephrine by the adrenal was studied in dogs. The epinephrine content of adrenal venous blood was assayed on the rat uterus, automatically stimulated. The infusion of epinephrine or norepinephrine at a rate which produced an increase in blood pressure inhibited the output of epinephrine by the adrenal. If the rate of infusion of catecholamines was too slow to increase the blood pressure, or if the increase in blood pressure was prevented by a pressure compensator, secretion of epinephrine was not inhibited. A good correlation exists between the per cent decrease in epinephrine secretion and the per cent increase in blood pressure produced by infusion of catecholamines. It appears that the inhibition of epinephrine secretion during infusion of catecholamines is produced reflexly by the induced increase in blood pressure. In two experiments the aortic epinephrine concentration exceeded the adrenal venous epinephrine concentration during infusion of epinephrine, suggesting an uptake of epinephrine by the adrenal gland.