Cardiovascular and Steroid Responses to Graded Haemorrhage in Rats with Adrenal Regeneration Hypertension

Blood pressure (BP) and plasma steroid responses to haemorrhage (2 ml + 1 ml + 1 ml at 20-min intervals) were assessed in sham-operated (SO) rats and in rats with adrenal regeneration hypertension (ARH). Experiments were carried out between 0700 and 1000 h (a.m.) and between 1400 and 1700 h (p.m.), because rats with ARH have BPs that are higher a.m. than p.m. There were no differences in the BP responses following haemorrhage in SO or ARH rats either a.m. or p.m., although ARH rats were unable to increase their plasma steroid levels. Pretreatment with captopril alone, d(CH₂)₅ DAVP alone, or captopril and d(CH₂)₅DAVP augmented the early hypotensive responses to haemorrhage but did not influence the later compensated levels of BP in either group of rats. There were no clear-cut a.m. to p.m. differences in the changes in BP in any of the drug-treated groups of SO or ARH rats. Under all conditions studied, the compensated level of systolic BP in ARH rats, 20 min after the final bleed, remained higher a.m. than p.m., indicating that this difference was not dependent on the renin-angiotensin system and vasopressin and suggesting that the sympathetic nervous system and/or other factors might be involved.     

Sympathetic neural control of integrated cardiovascular function: insights from measurement of human sympathetic nerve activity

Sympathetic neural control of cardiovascular function is essential for normal regulation of blood pressure and tissue perfusion. In the present review we discuss sympathetic neural mechanisms in human cardiovascular physiology and pathophysiology, with a focus on evidence from direct recordings of sympathetic nerve activity using microneurography. Measurements of sympathetic nerve activity to skeletal muscle have provided extensive information regarding reflex control of blood pressure and blood flow in conditions ranging from rest to postural changes, exercise, and mental stress in populations ranging from healthy controls to patients with hypertension and heart failure. Measurements of skin sympathetic nerve activity have also provided important insights into neural control, but are often more difficult to interpret since the activity contains several types of nerve impulses with different functions. Although most studies have focused on group mean differences, we provide evidence that individual variability in sympathetic nerve activity is important to the ultimate understanding of these integrated physiological mechanisms.     

Blood Markers of Inflammation,Neurodegeneration, and Cardiovascular Risk in Early Parkinson's Disease

Background

Recent studies point toward a significant impact of cardiovascular processes and inflammation on Parkinson's disease (PD) progression.

Objective

The aim of this study was to assess established markers of neuronal function, inflammation, and cardiovascular risk by high-throughput sandwich immune multiplex panels in deeply phenotyped PD.

Methods

Proximity Extension Assay technology on 273 markers was applied in plasma of 109 drug-naive at baseline (BL) patients with PD (BL, 2-, 4-, and 6-year follow-up [FU]) and 96 healthy control patients (HCs; 2- and 4-year FU) from the de novo Parkinson's cohort. BL plasma from 74 individuals (37 patients with PD, 37 healthy control patients) on the same platform from the Parkinson Progression Marker Initiative was used for independent validation. Correlation analysis of the identified markers and 6 years of clinical FU, including motor and cognitive progression, was evaluated.

Results

At BL, 35 plasma markers were differentially expressed in PD, showing downregulation of atherosclerotic risk markers, eg, E-selectin and ß₂-integrin. In contrast, we found a reduction of markers of the plasminogen activation system, eg, urokinase plasminogen activator. Neurospecific markers indicated increased levels of peripheral proteins of neurodegeneration and inflammation, such as fibroblast growth factor 21 and peptidase inhibitor 3. Several markers, including interleukin-6 and cystatin B, correlated with cognitive decline and progression of motor symptoms during FU. These findings were independently validated in the Parkinson Progression Marker Initiative.

Conclusions

We identified and validated possible PD plasma biomarker candidates for state, fate, and disease progression, elucidating new molecular processes with reduced endothelial/atherosclerotic processes, increased thromboembolic risk, and neuroinflammation. Further investigations and validation in independent and larger longitudinal cohorts are needed. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.     

Understanding the Links Between Cardiovascular Disease and Parkinson's Disease

Studies investigating the associations between genetic or environmental factors and Parkinson's disease (PD) have uncovered a number of factors shared with cardiovascular disease, either as risk factors or manifestations of cardiovascular disease itself. Older age, male sex, and possibly type 2 diabetes are examples. On the other hand, coffee consumption and physical activity are each associated with a lower risk of both PD and cardiovascular disease. This observation raises questions about the underlying pathophysiological links between cardiovascular disease and PD. There is evidence for common mechanisms in the areas of glucose metabolism, cellular stress, lipid metabolism, and inflammation. On the other hand, smoking and total/low-density lipoprotein cholesterol appear to have opposite associations with cardiovascular disease and PD. Thus, it is uncertain whether the treatment of cardiovascular risk factors will impact on the onset or progression of PD. The available data suggest that a nuanced approach is necessary to manage risk factors such as cholesterol levels once the associations are better understood. Ultimately, the choice of therapy may be tailored to a patient's comorbidity profile. This review presents the epidemiological evidence for both concordant and discordant associations between cardiovascular disease and PD, discusses the cellular and metabolic processes that may underlie these links, and explores the implications this has for patient care and future research. © 2019 International Parkinson and Movement Disorder Society     

Fos expression induced by changes in arterial pressure is localized in distinct,longitudinally organized columns of neurons in the rat midbrain periaqueductal gray

The distribution of neurons expressing Fos within the periaqueductal gray (FAG) following pharmacologically induced high or low blood pressure was examined to determine (1) if PAG neurons are responsive to changes in arterial pressure (AP) and (2) the relationship of these cells to the functionally defined hypertensive and hypotensive columns in PAG. Changes in AP differentially induced robust Fos expression in neurons confined to discrete, longitudinally organized columns within PAG. Increased AP produced extensive Fos-like immunoreactivity within the lateral PAG, beginning at the level of the oculomotor nucleus. At the level of the dorsal raphe, Fos expression induced by increased AP shifted dorsally, into the dorsolateral division of PAG; this pattern of Fos labeling was maintained throughout the caudal one-third of PAG. Double-labeling for Fos and nicotinamide adenine dinucleotide phosphate diaphorase confirmed that Fos-positive cells induced by increased AP were located in the dorsolateral division of PAG at these caudal levels. Fos positive cells were codistributed, but not colocalized, with nicotinamide adenine dinucleotide phosphate diaphorase-positive cells. Decreased AP evoked a completely different pattern of Fos expression. Fos-positive cells were predominantly located within the ventrolateral PAG region, extending from the level of the trochlear nucleus through the level of the caudal dorsal raphe. Double-labeling studies for Fos and serotonin indicated that only 1–2 double-labeled cells per section were present. Saline infusion resulted in very few Foslike immunoreactive cells, indicating that volume receptor activation does not account for Fos expression in PAG evoked by changes in AP. These results indicate that (1) substantial numbers of PAG neurons are excited by pharmacologically induced changes in AP and (2) excitatory barosensitive PAG neurons are anatomically segregated based on their responsiveness to a specific directional change in AP. © 1995 Wiley-Liss, Inc.     

Antihypertensive effects of L-tryptophan are not mediated by brain serotonin

L-Tryptophan produces a significant antihypertensive effect in spontaneously hypertensive rats while D-tryptophan does not change blood pressure. Both isomers of tryptophan significantly increase brain serotonin to the same extent at a time when the antihypertensive effect of L-tryptophan is maximal. Thus, the antihypertensive effects of L-tryptophan do not appear to be mediated by brain serotonin.     

Pressor and tachycardic responses evoked by microinjections of L-glutamate into the medial prefrontal cortex of unanaesthetized rats

The ventral medial prefrontal cortex (vMPFC) is involved in central cardiovascular control. In the present study, we studied the cardiovascular effects of injections of L-glutamate into the vMPFC of unanaesthetized rats and the mechanisms of these effects. Male Wistar rats were used and L-glutamate was microinjected in the vMPFC in a final volume of 200 nL. Microinjections of L-glutamate (9, 27, 81, 150 or 300 nmol) caused long-lasting, dose-related pressor and tachycardic responses in unanaesthetized rats. No differences were observed among cardiovascular responses when L-glutamate was injected into the three sub-areas that comprise the vMPFC, namely the prelimbic, the infralimbic and the dorsal peduncular cortices. No responses were observed when the dose of 81 nmol of L-glutamate was microinjected into surrounding structures such as the cingulate cortex area 1, the corpus callosum and the tenia tecta, indicating a predominant action on the vMPFC. The cardiovascular response to L-glutamate into the vMPFC was blocked by intravenous pretreatment with the ganglion blocker pentolinium (10 mg/kg, i.v.) or the beta1-adrenoceptor antagonist atenolol (1.5 mg/kg, i.v.), supporting the involvement of the cardiac sympathetic nervous system in the response to L-glutamate. Pretreatment with the muscarinic antagonist homatropine methyl bromide (1 mg/kg, i.v.) reduced the latency to the onset of the pressor and tachycardic responses to L-glutamate injected into the vMPFC without significant effects on response duration or maximum effect. We conclude that stimulation of the vMPFC with L-glutamate caused pressor and tachycardic responses in unanaesthetized rats, responses which were dependent on cardiac sympathetic nerve activation and were potentiated by blockade of peripheral muscarinic receptors.     

Cardiovascular effects of noradrenaline microinjected into the dorsal periaqueductal gray area of unanaesthetized rats

The periaqueductal grey area (PAG) is a mesencephalic region that is involved in the modulation of cardiovascular changes associated with behavioural responses. Among the neurotransmitters present in the PAG, noradrenaline (NA) is also known to be involved in central nervous system cardiovascular regulation. In the present study we report the cardiovascular effects of the microinjection of NA into the dorsal portion of the PAG (dPAG) of unanaesthetized rats and the peripheral mechanism involved in their mediation. Injection of NA in the dPAG of unanaesthetized rats evoked a dose-dependent pressor response accompanied by bradycardia. The magnitude of the pressor responses was higher at more rostral sites in the dPAG and decreased when NA was injected into the caudal portion of the dPAG. The responses to NA were markedly reduced in urethane-anaesthetized rats. The pressor response was potentiated by i.v. pretreatment with the ganglion blocker pentolinium and blocked by i.v. pretreatment with the vasopressin antagonist dTyr(CH2)5(Me)AVP. The results suggest that activation of noradrenergic receptors within the dPAG can evoke pressor responses, which are mediated by acute vasopressin release.     

Longitudinal relation between blood pressure,antihypertensive use and cerebral blood flow,using arterial spin labelling MRI

Consistent cerebral blood flow (CBF) is fundamental to brain function. Cerebral autoregulation ensures CBF stability. Chronic hypertension can lead to disrupted cerebral autoregulation in older people, potentially leading to blood pressure levels interfering with CBF. This study tested whether low BP and AHD use are associated with contemporaneous low CBF, and whether longitudinal change in BP is associated with change in CBF, using arterial spin labelling (ASL) MRI, in a prospective longitudinal cohort of 186 community-dwelling older individuals with hypertension (77 ± 3 years, 53% female), 125 (67%) of whom with 3-year follow-up. Diastolic blood pressure, systolic blood pressure, mean arterial pressure, and pulse pressure were assessed as blood pressure parameters. As additional cerebrovascular marker, we evaluated the ASL signal spatial coefficient of variation (ASL SCoV), a measure of ASL signal heterogeneity that may reflect cerebrovascular health. We found no associations between any of the blood pressure measures and concurrent CBF nor between changes in blood pressure measures and CBF over three-year follow-up. Antihypertensive use was associated with lower grey matter CBF (−5.49 ml/100 g/min, 95%CI = −10.7|−0.27, p = 0.04) and higher ASL SCoV (0.32 SD, 95%CI = 0.12|0.52, p = 0.002). These results warrant future research on the potential relations between antihypertensive use and cerebral perfusion.     

An Autopsy Case of Binswanger's Disease without Hypertension and Associated with Cerebral Infarction in the Terminal Stage

Abstract: We report here an autopsy case of Binswanger's disease (BD) without hypertension and associated with cerebral infarction in the terminal stage. The female patient, who was 74 years old at the time of death, had initially demonstrated manic-depressive disorder-like mental disorder, followed by dementia and neurological deficits. A brain CT scan showed white matter low attenuation bilaterally and symmetrically. BD was clinically diagnosed despite the lack of hypertension. In the terminal stage, she suffered an infarction in the left anterior cerebral artery region, and died of pneumonia. Neuropathologically, we found the infarction of the left anterior cerebral artery region, demyelination, fibrillary gliosis, lacunae and arteriosclerosis of the small arteries and arterioles in the white matter.     

Angiotensinogen Gene Polymorphism Predicts Hypertension,and Iridological Constitutional Classification Enhances the Risk for Hypertension in Koreans

This study investigated the relationship between iridological constitution and angiotensinogen (AGN) gene polymorphism in hypertensives. In addition to angiotensin converting enzyme gene, AGN genotype is also one of the most well studied genetic markers of hypertension. Furthermore, iridology, one of complementary and alternative medicine, is the diagnosis of the medical conditions through noting irregularities of the pigmentation in the iris. Iridological constitution has a strong familial aggregation and is implicated in heredity. Therefore, the study classified 87 hypertensive patients with familial history of cerebral infarction and controls (n = 88) according to Iris constitution, and determined AGN genotype. As a result, the AGN/TT genotype was associated with hypertension (χ² = 13.413, p < .05). The frequency of T allele was 0.92 in patients and 0.76 in controls (χ² = 13.159, p < .05). In addition, iridological constitutional classification increased the relative risk for hypertension in the subjects with AGN/T allele. These results suggest that AGN polymorphism predicts hypertension, and iridological constitutional classification enhances the risk for hypertension associated with AGN/T in a Korean population.