Robert E. Shade

Texas Biomedical Research Institute

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Laura A. Cox

Wake Forest University

Leonard Share

University of Tennessee Health Science Center

Derek A. Denton

Environmental Health

Joseph R. Haywood

Michigan State University

Jeremy P. Glenn

Texas Biomedical Research Institute

Carmen Hinojosa‐Laborde

United States Army Institute of Surgical Research

J. R. Blair‐West

Florey Institute of Neuroscience and Mental Health

Shifra Birnbaum

Texas Biomedical Research Institute

Peter T. Fox

The University of Texas Health Science Center at San Antonio

Kimberly D. Spradling‐Reeves

Wake Forest University

Cooperative Institutions

Texas Biomedical Research Institute

The University of Texas Health Science Center at San Antonio

The University of Texas at San Antonio

United States Army Institute of Surgical Research

University of Tennessee Health Science Center

The University of Texas Health Science Center at Houston

University of Melbourne

Florey Institute of Neuroscience and Mental Health

Joint Base San Antonio

University of Tennessee at Knoxville

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Spectral analysis of blood pressure and heart rate variability in baboons with a normal, low or high RBC sodium‐lithium countertransport phenotype

The FASEB Journal (2007)

Nathan E. Lee Carmen Hinojosa‐Laborde Laura A. Cox JR Haywood Robert E. Shade

High Red blood cell sodium-lithium countertransport activity (SLC) has consistently been associated with inherited, salt-sensitive hypertension in humans. The objective of this study was to compare blood pressure variability by spectral analysis in High SLC baboons vs Low or Normal SLC baboons. Power spectral density of blood pressure and heart rate variability was initially calculated for beat-to-beat data interpolated over 1 second intervals for 3 24-h periods in Normal SLC baboons on a low sodium intake (20 mmol Na/day). Spectral density of variability was calculated for low (0.025–0.39 Hz, LF), mid (0.040–0.19 hz, MF) and high (0.20–0.50 Hz, HF) frequency ranges for each hour of a 24-h period except for the period of 1300–1600 h where activity related to feeding and husbandry procedures prevented collection of adequate stationary data for spectral analysis. This analysis indicated that blood pressure and heart rate variability in the LF range achieved a statistically significant nadir for log transformed pooled data for the 0000–0600 period vs 0800–1300 and 1600–2400 time periods. Subsequent spectral analysis of blood pressure and heart rate variability for the 0000–01000 nadir time period revealed no significant differences between normal, low, or high SLC baboons for log transformed spectral analysis data for low Na diet, low Na+Ang, high Na+Ang or high Na. Thus, although high SLC baboons had significantly larger increases in blood pressure than either normal of low SLC baboons for each combination of diet and Ang treatment power spectral analysis of blood pressure variability for the 0000–0100 h time period did provide any indication that sympathetic mechanisms contributed to these differences.

Spectral Analysis

Beat (acoustics)

10.1096/fasebj.21.5.a514-d

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Neuroimaging evidence implicating cerebellum in support of sensory/cognitive processes associated with thirst

Proceedings of the National Academy of Sciences (2000)

Lawrence M. Parsons Derek A. Denton Gary F. Egan Michael J. McKinley Robert E. Shade

Recent studies implicate the cerebellum, long considered strictly a motor control structure, in cognitive, sensory, and affective phenomenon. The cerebellum, a phylogenetically ancient structure, has reciprocal ancient connections to the hypothalamus, a structure important in vegetative functions. The present study investigated whether the cerebellum was involved in vegetative functions and the primal emotions engendered by them. Using positron emission tomography, we examined the effects on the cerebellum of the rise of plasma sodium concentration and the emergence of thirst in 10 healthy adults. The correlation of regional cerebral blood flow with subjects' ratings of thirst showed major activation in the vermal central lobule. During the development of thirst, the anterior and posterior quadrangular lobule, lingula, and the vermis were activated. At maximum thirst and then during irrigation of the mouth with water to alleviate dryness, the cerebellum was less activated. However, 3 min after drinking to satiation, the anterior quadrangular lobule and posterior cerebellum were highly activated. The increased cerebellar activity was not related to motor behavior as this did not occur. Instead, responses in ancient cerebellar regions (vermis, fastigal nucleus, archicerebellum) may be more directly related to vegetative and affective aspects of thirst experiences, whereas activity in neocerebellar (posterior) regions may be related to sensory and cognitive aspects. Moreover, the cerebellum is apparently not involved in the computation of thirst per se but rather is activated during changes in thirst/satiation state when the brain is “vigilant” and is monitoring its sensory systems. Some neocerebellar activity may also reflect an intentionality for gratification by drinking inherent in the consciousness of thirst.

Cerebellar vermis

10.1073/pnas.040555497

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Linkage of Essential Hypertension to the Angiotensinogen Locus in Mexican Americans

Hypertension (1997)

Larry D. Atwood Candace M. Kammerer Paul B. Samollow James E. Hixson Robert E. Shade

Abstract Essential hypertension has been linked to a highly polymorphic marker at the angiotensinogen locus, and association with a polymorphism in this locus has been found in some populations. We tested the hypothesis that these same polymorphic markers are linked to essential hypertension in Mexican Americans. The data comprised all the affected relative pairs in 46 extended families chosen at random from a low-income barrio in San Antonio. Specifically, we searched for linkage by testing for excessive marker alleles shared identical by descent (IBD) among hypertensive relative pairs. When women taking oral contraceptives or hormones were excluded, the affected relative pairs shared a significant excess of alleles IBD for the highly heterozygous GT repeat polymorphism ( P =.038) and were marginally significant for the M235T variant ( P =.079), which has a much lower heterozygosity (0.43 versus 0.85 for the GT repeat). We also assayed plasma levels of angiotensinogen and, using likelihood methods, found no significant association ( P =.43) between plasma levels of angiotensinogen and M235T genotypes. These results support the linkage of essential hypertension to the angiotensinogen locus but do not indicate a specific role for the M235T variant.

Essential hypertension

Genetic linkage

Linkage (software)

10.1161/01.hyp.30.3.326

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Citations (46)

Effect of 30 per cent maternal nutrient restriction from 0.16 to 0.5 gestation on fetal baboon kidney gene expression

The Journal of Physiology (2006)

Laura A. Cox Mark J. Nijland Jeffrey S. Gilbert Natalia Schlabritz‐Loutsevitch Gene B. Hubbard

Previous studies in rodents and sheep show that maternal nutrient restriction during pregnancy alters fetal renal development. To date, no studies using fetal baboon RNA with human Affymetrix gene chips have been published. In the present study we have (1) evaluated the specificity of the Affymetrix human gene array 'Laboratory on a Chip' system for use with fetal baboon mRNA and (2) investigated the effects of moderate maternal global nutrient restriction (NR; 70% of ad libitum animals) from early (30 days gestation (dG)) to mid-gestation (90 dG; term = 184 dG) on the fetal baboon kidney. Morphometric and blood measurements were made on 12 non-pregnant baboons before they were bred. All baboons were fed ad libitum until 30 days pregnant, at which time six control baboons continued to feed ad libitum (control - C) while six received 70% of the C diet on a weight adjusted basis. Fetal kidneys were collected following caesarean section at 90 dG, with samples flash frozen and fixed for histological assessment. Fetal hip circumference was decreased in the NR group (68 +/- 2 versus 75 +/- 2 mm), while fetal body weight and all other measurements of fetal size were not different between C and NR at 90 dG. Maternal body weight was decreased in the NR group (12.16 +/- 0.34 versus 13.73 +/- 0.55 kg). Having established the specificity of the Affymetrix system for fetal baboon mRNA, gene expression profiling of fetal kidneys in the context of our maternal nutrient restriction protocol shows that NR resulted in a down-regulation of genes in pathways related to RNA, DNA and protein biosynthesis, metabolism and catabolism. In contrast, genes in cell signal transduction, communication and transport pathways were up-regulated in the NR group. These changes indicate that even a moderate level of maternal global NR impacts fetal renal gene pathways. Our histological assessment of renal structure indicates decreased tubule density within the cortex of NR kidneys compared with controls. The number of glomerular cross-sections per unit area were unaffected by NR, suggesting that tubule tortuosity and/or tubule length was decreased in the NR kidney. Taken together the changes indicate that NR results in accelerated fetal renal differentiation. The negative impact of poor maternal nutrition on the fetal kidney may therefore be in part due to shortening of critical phases of renal growth resulting in decreased functional capacity in later life. These findings may have important implications for postnatal renal function, thereby contributing to the observed increased predisposition to hypertension and renal disease in the offspring of nutrient restricted mothers.

Intrauterine growth restriction

10.1113/jphysiol.2006.106872

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Citations (77)

Synergy between angiotensin and aldosterone in evoking sodium appetite in baboons

AJP Regulatory Integrative and Comparative Physiology (2002)

Robert E. Shade J. R. Blair‐West K. Dee Carey Lisa J. Madden R. S. Weisinger

The synergy between ANG II and aldosterone (Aldo) in the induction of salt appetite, extensively studied in rats, has been tested in baboons. ANG II was infused intracerebroventricularly at 0.5 or 1.0 μg/h; Aldo was infused subcutaneously at 20 μg/h. Separate infusions over 7 days had no significant effect on the daily intake of 300 mM NaCl. Concurrent infusions, however, increased daily NaCl intake ∼10-fold and daily water intake ∼2.5-fold. In addition, the combined infusions caused 1) a reduction in daily food intake, 2) changes in blood composition indicative of increased vasopressin release, and 3) changes of urinary excretion rates of cortisol and Aldo indicative of increased ACTH release. Arterial blood pressure, measured in two baboons, rose during concurrent ANG II and Aldo treatment. These results indicate a potent synergy between central ANG II and peripheral Aldo in stimulating salt appetite in baboons. At the same time, other ANG II-specific brain mechanisms concerned with water intake, food intake, vasopressin release, ACTH release, and blood pressure regulation appear to have been activated by the same type of synergy. These central enhancement processes have never been previously demonstrated in primates.

Mineralocorticoid

sed

10.1152/ajpregu.00248.2002

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Effects of Renal Arterial Infusion of Sodium and Potassium on Renin Secretion in the Dog

Circulation Research (1972)

Robert E. Shade James O. Davis J. A. Johnson Robert T. Witty

The nonfiltering kidney model was used to determine whether sodium or potassium inhibits renin secretion in the absence of a functional macula densa in dogs with thoracic inferior vena caval constriction. The control rate of renin secretion was high, and decreases were readily recognized. After control observations, hypertonic sodium chloride or hypertonic potassium chloride was infused into the renal artery for 1 hour, and renin secretion was measured at 15-minute intervals. An increase in renal venous plasma sodium concentration from 141 to 154-158 mEq/liter caused no change in renin secretion for the first 45 minutes of infusion in dogs with a nonfiltering kidney. In contrast, dogs with thoracic caval constriction but with a filtering kidney showed a striking decrease in renin secretion during intrarenal sodium infusion (3,097 to 1,061 ng angiotensin/min, P <0.02). An increase in renal venous plasma potassium concentration from 3.9 to 6.1 mEq/liter in one group of dogs and from 4.9 to 8.3 mEq/liter in a second group also caused no change in renin secretion in the nonfiltering kidney of dogs with thoracic caval constriction. However, in dogs with thoracic caval constriction and a filtering kidney, potassium infusion decreased renin secretion (1,952 to 984 ng angiotensin/min, P <0.05). In all experiments, infusion of sodium chloride or potassium chloride failed to produce a significant change in renal blood flow, arterial blood pressure, or inferior vena caval pressure. Therefore, no evidence was obtained for a vascular action or a direct effect of sodium or potassium on the juxtaglomerular cells, and the data are consistent with an action mediated by the renal tubular system.

Plasma renin activity

Constriction

Macula densa

10.1161/01.res.31.5.719

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Citations (61)

325 Blood pressure and the kidney cortex transcriptome response to high sodium diet challenge in female nonhuman primates

Journal of Clinical and Translational Science (2022)

Angelica M. Riojas Kimberly D. Spradling‐Reeves Robert E. Shade Sobha Puppala Clinton L. Christensen

OBJECTIVES/GOALS: The goal of this study was to understand the impact of a high sodium diet on gene networks in the kidney that correlate with blood pressure in female primates, and translating findings to women. METHODS/STUDY POPULATION: Sodium-naÃ¯ve female baboons (n=7) were fed a low-sodium (LS) diet for 6 weeks followed by a high sodium (HS) diet for 6 weeks. Sodium intake, serum 17 beta-estradiol, and ultrasound-guided kidney biopsies for RNA-Seq were collected at the end of each diet. Blood pressure was continuously measured for 64-hour periods throughout the study by implantable telemetry devices. Weighted gene coexpression network analysis was performed on RNA-Seq data to identify transcripts correlated with blood pressure on each diet. Network analysis was performed on transcripts highly correlated with BP, and in silico findings were validated by immunohistochemistry of kidney tissues. RESULTS/ANTICIPATED RESULTS: On the LS diet, Na+ intake and serum 17 beta-estradiol concentration correlated with BP. Cell type composition of renal biopsies was consistent among all animals for both diets. Kidney transcriptomes differed by diet; analysis by unbiased weighted gene co-expression network analysis revealed modules of genes correlated with BP on the HS diet. Network analysis of module genes showed causal networks linking hormone receptors, proliferation and differentiation, methylation, hypoxia, insulin and lipid regulation, and inflammation as regulators underlying variation in BP on the HS diet. Our results show variation in BP correlated with novel kidney gene networks with master regulators PPARG and MYC in female baboons on a HS diet. DISCUSSION/SIGNIFICANCE: Previous studies in primates to identify molecular networks dysregulated by HS diet focused on males. Current clinical guidelines do not offer sex-specific treatment plans for sodium sensitive hypertension. This study leveraged variation in BP as a first step to identify correlated kidney regulatory gene networks in female primates after a HS diet.

10.1017/cts.2022.182

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A PET study of the neural correlates of CO2-induced air hunger

NeuroImage (2000)

Mario Liotti S.K. Brannan Rachel Robillard Bart Albpenalop Lisa Madden

10.1016/s1053-8119(00)91692-6

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High-frequency burst vagal nerve simulation therapy in a natural primate model of genetic generalized epilepsy

Epilepsy Research (2017)

C.Á. Szabó Felipe S. Salinas Alex M. Papanastassiou Jason Begnaud Maryam Ravan

Vagus Nerve Stimulation

Tolerability

10.1016/j.eplepsyres.2017.10.010

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Citations (25)

Brain responses associated with consciousness of breathlessness (air hunger)

Proceedings of the National Academy of Sciences (2001)

Mario Liotti Stephen Brannan Gary F. Egan Robert E. Shade Lisa Madden

Little is known about the physiological mechanisms subserving the experience of air hunger and the affective control of breathing in humans. Acute hunger for air after inhalation of CO 2 was studied in nine healthy volunteers with positron emission tomography. Subjective breathlessness was manipulated while end-tidal CO 2 - was held constant. Subjects experienced a significantly greater sense of air hunger breathing through a face mask than through a mouthpiece. The statistical contrast between the two conditions delineated a distributed network of primarily limbic/paralimbic brain regions, including multiple foci in dorsal anterior and middle cingulate gyrus, insula/claustrum, amygdala/periamygdala, lingual and middle temporal gyrus, hypothalamus, pulvinar, and midbrain. This pattern of activations was confirmed by a correlational analysis with breathlessness ratings. The commonality of regions of mesencephalon, diencephalon and limbic/paralimbic areas involved in primal emotions engendered by the basic vegetative systems including hunger for air, thirst, hunger, pain, micturition, and sleep, is discussed with particular reference to the cingulate gyrus. A theory that the phylogenetic origin of consciousness came from primal emotions engendered by immediate threat to the existence of the organism is discussed along with an alternative hypothesis by Edelman that primary awareness emerged with processes of ongoing perceptual categorization giving rise to a scene [Edelman, G. M. (1992) Bright Air, Brilliant Fire (Penguin, London)].

Limbic lobe

Lingual gyrus

Gyrus

Limbic system

Middle temporal gyrus

Fusiform gyrus

10.1073/pnas.98.4.2035

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Citations (284)