Role of endothelin-1 in age-dependent cerebrovascular hypotensive responses after brain injury

1999 ◽  
Vol 277 (5) ◽  
pp. H1884-H1894 ◽  
Author(s):  
William M. Armstead

This study was designed to compare the effect of fluid percussion brain injury (FPI) on the hypotensive cerebrovascular response in newborn and juvenile pigs as a function of time postinsult and to determine the role of endothelin-1 (ET-1) in any age-dependent differences in hypotensive cerebrovascular regulation after injury. Ten minutes of hypotension (10–15 ml blood/kg) decreased mean arterial blood pressure uniformly in both groups (∼45%). In the newborn, hypotensive pial artery dilation (PAD) was blunted within 1 h, remained diminished for at least 72 h, but was resolved within 168 h postinjury (66 ± 4, 69 ± 4, 71 ± 4, and 64 ± 4% inhibition at 1, 4, 8, and 72 h post-FPI). During normotension, regional cerebral blood flow (rCBF) was decreased by FPI, and hypotension further reduced the already decremented rCBF for at least 72 h. Cerebrospinal fluid (CSF) ET-1 was increased from 26 ± 4 to 206 ± 25 pg/ml within 72 h post-FPI, whereas an ET-1 antagonist partially restored impaired hypotensive PAD and altered hypotensive rCBF. In contrast, hypotensive PAD and altered CBF were only inhibited for 4 h post-FPI in the juvenile (56 ± 3 and 34 ± 4% inhibition at 1 and 4 h post-FPI). CSF ET-1 was only increased from 27 ± 4 to 67 ± 9 pg/ml at 4 h, whereas the concentration returned to preinjury value by 8 h post-FPI. ET-1 antagonism similarly partially restored impaired hypotensive PAD and altered hypotensive rCBF. These data show that FPI disturbs cerebral autoregulation during hypotension both to a greater magnitude and for a longer duration in the newborn than in the juvenile. These data suggest that the greater FPI-induced ET-1 release in the newborn could contribute to age-dependent differences in impaired hypotensive cerebral autoregulation after FPI.

Endocrinology ◽  
2009 ◽  
Vol 150 (5) ◽  
pp. 2382-2387 ◽  
Author(s):  
Karim Sabrane ◽  
Markus-N. Kruse ◽  
Alexandra Gazinski ◽  
Michaela Kuhn

Atrial natriuretic peptide (ANP), via its guanylyl cyclase (GC)-A receptor, plays a key role in the regulation of arterial blood pressure (ABP) and volume. Endothelial-restricted deletion of GC-A in mice [endothelial cell (EC) GC-A knockout (KO)] resulted in hypervolemic hypertension, demonstrating that the endothelium participates in the hypotensive and hypovolemic actions of ANP. Published studies showed that ANP modulates the release of the vasoactive factors nitric oxide (NO) and endothelin-1 (ET-1) from cultured endothelia. Based on these observations, we examined the role of these endothelial factors in ANP-dependent vasodilatation (studied in isolated arteries) and chronic regulation of ABP (measured in awake mice by tail-cuff plethysmography). ANP induced concentration-dependent vasorelaxations of aortic, carotid, and pulmonary arteries. These responses were not different between control and EC GC-A KO mice, and were significantly enhanced after inhibition of NO synthase [by N(G)-nitro-l-arginine-methyl ester]. Intravenous administration of N(G)-nitro-l-arginine-methyl ester to conscious mice significantly increased ABP. The extent of these hypertensive reactions was similar in EC GC-A KO mice and control littermates (increases in systolic blood pressure by ∼25 mm Hg). Conversely, antagonism of ET-1/endothelin-A receptors with BQ-123 reduced ABP significantly and comparably in both genotypes (by ∼11 mm Hg). Finally, the vascular and tissue expression levels of components of the NO system and of immunoreactive ET-1 were not different in control and EC GC-A KO mice. We conclude that the endothelium, but not modulation of endothelial NO or ET-1, participates in the chronic regulation of ABP by ANP.


2001 ◽  
Vol 2 (3) ◽  
pp. 175-185 ◽  
Author(s):  
Catherine J. Kirkness ◽  
Pamela H. Mitchell ◽  
Robert L. Burr ◽  
David W. Newell

The purpose of this study was to examine the relationship between Czosnyka and others’ Pressure Reactivity Index (PRx) and neurologic outcome in patients with acute brain injury, including traumatic brain injury (TBI) and cerebrovascular pathology. PRx measures the correlation between arterial blood pressure and intracranial pressure waves and may reflect cerebral autoregulation in response to blood pressure changes. A negative PRx reflects intact cerebrovascular response, whereas a positive PRx reflects impaired response. Positive PRx has been shown to correlate with poorer outcome in individuals with TBI, but these findings have not been confirmed by replication in other studies, nor have PRx values been reported for individuals with cerebrovascular pathology. In this study, PRx was determined in 52 patients with TBI (n = 27) or cerebrovascular pathology (n = 25). Hierarchical linear regression was used to evaluate the contribution of PRx to outcome, controlling for age and Glasgow Coma Scale score. Analysis of all subjects together did not support the previously reported relationship between PRx and outcome. However, for those with TBI, positive PRx was a significant predictor of negative outcome (P = 0.03). For those with cerebrovascular pathology, the effect was not significant (P = 0.10) and was in the opposite direction. For individuals with TBI, PRx may provide useful information related to cerebral autoregulation that is predictive of outcome. The meaning of PRx in individuals with cerebrovascular pathology is unclear, and further study is needed to examine the paradoxical findings observed.


Cephalalgia ◽  
1982 ◽  
Vol 2 (1) ◽  
pp. 15-18 ◽  
Author(s):  
Annette Æbelholt Krabbe ◽  
Jes Olesen

Regional cerebral blood flow (rCBF) was measured using the intra-arterial 133Xe technique in 35 or 256 areas of a hemisphere. In seven patients rCBF was measured in the resting state and following intracarotid (i.c.) infusion of histamine 10–50 μg/min. In four patients histamine was infused intravenously in a dose of 25–40 μg/min. Histamine caused no significant change in mean arterial blood pressure or arterial PCO2. There was no significant change in mean hemispheric blood flow during i.v. or i.c. histamine infusion. No change in the regional distribution of hemispheric blood flow was observed. Experimental histamine headache is most likely of extracranial origin.


1987 ◽  
Vol 253 (4) ◽  
pp. H956-H964 ◽  
Author(s):  
C. F. Miller ◽  
M. J. Breslow ◽  
R. M. Shapiro ◽  
R. J. Traystman

The role of reduced arterial blood pressure (MAP) in decreasing cerebral blood flow (CBF) during endotoxemia was studied in pentobarbital-anesthetized pigs. Microspheres (15 microns diam) were used to measure regional CBF changes during MAP manipulations in animals with and without endotoxin. Endotoxin (0.2 mg/kg iv) decreased MAP to 50 mmHg and decreased blood flow to the cortex and cerebellum without affecting cerebral cortical oxygen consumption (CMRO2). Elevating MAP from 50 to 70 mmHg during endotoxemia with norepinephrine (1.82 +/- 0.58 micrograms . kg-1 . min-1, iv) did not change cortical blood flow or CMRO2 but increased cerebellar blood flow. Brain stem blood flow was not affected by endotoxin or norepinephrine. When MAP was decreased to 50 mmHg by hemorrhage without endotoxin, no change in blood flow to cortex, cerebellum, or brain stem was observed from base-line levels. These results suggest that decreased MAP below a lower limit for cerebral autoregulation does not account for the decreased CBF observed after endotoxin.


2020 ◽  
Vol 129 (6) ◽  
pp. 1310-1323
Author(s):  
Jennifer L. Magnusson ◽  
Craig A. Emter ◽  
Kevin J. Cummings

The role of serotonin in arterial blood pressure (ABP) regulation across states of vigilance is unknown. We hypothesized that adult rats devoid of CNS serotonin (TPH2−/−) have low ABP in wakefulness and NREM sleep, when serotonin neurons are active. However, TPH2−/− rats experience higher ABP than TPH2+/+ rats in wakefulness and REM only, a phenotype present only in older males and not females. CNS serotonin may be critical for preventing high ABP in males with aging.


1984 ◽  
Vol 4 (1) ◽  
pp. 107-109 ◽  
Author(s):  
E. Shohami ◽  
A. Sidi

The effect of haemorrhagic hypotension on the levels of prostaglandin E2 (PGE2), thromboxane B2 (TXB2), and 6-keto prostaglandin F1α (6-keto-PGF1α) in cortical tissue of rats was studied. Lightly anesthetized rats were subjected to steady-state hypotension for 15 min, with a mean arterial blood pressure of 80, 60, and 40 mm Hg, and compared to a control group of normotensive rats. No significant change was found in the levels of PGE2 and TXB2. The level of 6-keto-PGF1α increased from 7.8 ± 0.9 to 14.1 ± 1.9 pg/mg protein (p < 0.02) at 80 mm Hg. Our findings suggest that prostacyclin, which is a potent vasodilator, might play a role in setting the lower limit of the autoregulation range.


2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Masayuki Satoh ◽  
Ken Nagata ◽  
Hidekazu Tomimoto

Objects. We investigated the role of the fusiform cortex in music processing with the use of PET, focusing on the perception of sound richness.Method. Musically naïve subjects listened to familiar melodies with three kinds of accompaniments: (i) an accompaniment composed of only three basic chords (chord condition), (ii) a simple accompaniment typically used in traditional music text books in elementary school (simple condition), and (iii) an accompaniment with rich and flowery sounds composed by a professional composer (complex condition). Using a PET subtraction technique, we studied changes in regional cerebral blood flow (rCBF) in simple minus chord, complex minus simple, and complex minus chord conditions.Results. The simple minus chord, complex minus simple, and complex minus chord conditions regularly showed increases in rCBF at the posterior portion of the inferior temporal gyrus, including the LOC and fusiform gyrus.Conclusions. We may conclude that certain association cortices such as the LOC and the fusiform cortex may represent centers of multisensory integration, with foreground and background segregation occurring at the LOC level and the recognition of richness and floweriness of stimuli occurring in the fusiform cortex, both in terms of vision and audition.


Sign in / Sign up

Export Citation Format

Share Document