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Biomedical subjects

John E Hall

Publications and source records attributed to John E Hall.

At least 37 records · Page 2Linked to original sources
PubMed2004

Role of adrenergic activity in pressor responses to chronic melanocortin receptor activation.

Acute studies have shown that MC3/4-R stimulation increases sympathetic activity, but the role of adrenergic activation in mediating the cardiovascular and renal responses to chronic melanocortin 3- and 4-receptor (MC3/4-R) activation is unknown. The present study tested whether chronic MC3/4-R activation raises blood pressure and whether these changes are attenuated by alpha1+beta-adrenergic blockade. Rats were instrumented with an intracerebroventricular (ICV) cannula and arterial and venous catheters for measurements of mean arterial pressure (MAP) and heart rate (HR) 24 hours per day, and intravenous infusions. After control measurements, rats were intravenously infused with either saline vehicle (n=7) or alpha1+ beta-adrenergic antagonists (n=6, terazosin+propranolol, 10 mg/kg per day each) for 21 days. Five days after starting the vehicle or adrenergic blockade, the MC3/4-R agonist, MTII (10 ng/h), was infused ICV for 11 days followed by a 5-day recovery period. Another group of rats was infused with the adrenergic antagonists for 21 days but received the saline vehicle ICV for 11 days (n=7). MC3/4-R activation decreased food intake from 21+/-1 to 8+/-2 g/d by day 3 of MC3/4-R activation, and increased MAP and HR by an average of 8+/-2 mm Hg and 9+/-5 bpm, respectively. Adrenergic blockade did not alter the MC3/4-R-mediated decrease in food intake but abolished the increases in MAP and HR (1+/-2 mm Hg and -12+/-5 bpm, respectively, compared with control). ICV vehicle infusion during adrenergic blockade did not alter food intake or MAP. Glomerular filtration rate was unchanged in both the vehicle-infused and adrenergic blocked rats during MC3/4-R activation. These results indicate that the chronic actions of MC3/4-R activation on MAP and HR are mediated by adrenergic activation.

Adrenergic Antagonists↗
PubMed2004

Is obesity a major cause of chronic kidney disease?

Excess weight gain is a major risk factor for essential hypertension and for end-stage renal disease (ESRD). Obesity raises blood pressure by increasing renal tubular sodium reabsorption, impairing pressure natriuresis, and causing volume expansion because of activation of the sympathetic nervous system and renin-angiotensin system and by physical compression of the kidneys, especially when visceral obesity is present. Obesity also causes renal vasodilation and glomerular hyperfiltration that initially serve as compensatory mechanisms to maintain sodium balance in the face of increased tubular reabsorption. In the long-term, however, these changes, along with the increased systemic arterial pressure, create a hemodynamic burden on the kidneys that causes glomerular injury. With prolonged obesity, there is increasing urinary protein excretion and gradual loss of nephron function that worsens with time and exacerbates hypertension. With the worsening of metabolic disturbances and the development of type II diabetes in some obese patients, kidney disease progresses much more rapidly. Weight reduction is an essential first step in the management of obesity, hypertension, and kidney disease. Special considerations for the obese patient, in addition to adequately controlling the blood pressure, include correction of the metabolic abnormalities and protection of the kidneys from further injury.

Diabetes Mellitus↗
PubMed2004

Increased expression of vascular endothelial growth factor and capillary density in hearts of spontaneously hypertensive rats.

OBJECTIVE: The role of VEGF in vascular remodeling of target organs exposed to chronic hypertension is poorly understood. The authors compared capillary density (CD), capillary-to-fiber ratio (C/F), and VEGF mRNA expression in the hearts (left ventricle [LV]), and skeletal muscles (soleus and anterior tibialis [AT]) of 18-week-old male spontaneously hypertensive rats (SHR) and age-matched male Wistar-Kyoto (WKY) and Sprague-Dawley (SD) rats. METHODS: CD or C/F in LV, soleus, and AT of SHR, WKY, and SD rats was determined by analysis of randomly acquired digital images of cryosections stained with FITC-conjugated GS-I lectin. VEGF mRNA expressions in the tissues were determined by Northern blot. RESULTS: VEGF mRNA expressions in LV of SHR were 3.84- and 5.05-fold higher, compared to SD and WKY rats, respectively (n = 6; p < .01). There were no significant differences in VEGF mRNA expression in soleus or AT among SHR, WKY, and SD rats (p > .05). CD in LV of SHR (4975 +/- 167) was significantly higher than WKY or SD rats, 4151 +/- 169 and 3807 +/- 187 mm(-2), respectively (p < .05). In LV of SHR, C/F increased (35%) more significantly than CD (increased 20%), compared to WKY rats. CD, or C/F in soleus or AT of SHR was similar to that observed in WKY or 8D rats. CONCLUSIONS: VEGF expression, CD, and C/F in the heart (LV) of SHR are significantly increased, compared to WKY and SD rats. The data are consistent with the possibility that VEGF may contribute to capillary growth as a compensatory response to hypertension.

Animals↗
PubMed2004

Underweight rather than overweight is associated with higher prevalence of hypertension: BP vs BMI in haemodialysis population.

BACKGROUND: Recent surveys have reported a higher prevalence of hypertension and obesity in the haemodialysis population, suggesting a possible link between these two parameters. Alternatively, malnutrition through proinflammatory and antiendothelial mechanisms may contribute to hypertension in malnourished, underweight patients on haemodialysis, whereas the converse may be true in overweight patients. METHODS: The relationship between blood pressure (BP) and body mass index (BMI) was examined in 1010 patients on chronic haemodialysis using univariate and multivariate analyses. RESULTS: Based on a systolic BP of >150 mmHg, 38% were hypertensive in the post-dialysis period. A similar figure for a diastolic BP of >90 mmHg was 21%. Unlike in the general population, there was no positive correlation between BP and BMI in simple regression analysis (r = -0.13, P = 0.0005). The percentage of patients with systolic hypertension was higher among the underweight (BMI <20) than the normal weight (BMI 20-27.5) or overweight patients (BMI >27.5) and were 35, 29 and 20%, respectively. Furthermore, a negative correlation, albeit weak, existed between systolic BP and markers of nutrition such as serum prealbumin (r = -0.10, P = 0.03) and serum creatinine (r = -0.12, P = 0.008), suggesting a plausible link between impaired nutrition and elevated BP. In multiple regression analysis, the lack of a positive correlation between BP and BMI persisted (r = -0.16, P = 0.0007) in spite of adjusting for case-mix characteristics and parameters related to BP and nutrition. CONCLUSIONS: We demonstrate for the first time that, unlike the general population, no positive correlation exists between BP and increasing BMI in haemodialysis patients. Further analysis is necessary to verify our observation and to test the possibility of whether nutritional improvement would aid in the better control of hypertension in dialysis patients.

Adult↗
PubMed2004

Cytokine gene expression profiles in kidney medulla and cortex of obese hypertensive dogs.

BACKGROUND: The molecular mechanisms linking abnormal kidney function and obesity hypertension are poorly understood. This study compared gene expression profiles in the kidney medulla and cortex of obese and lean dogs. METHODS: Lean dogs (N= 4) were fed a standard kennel ration and obese dogs (N= 4) were fed the standard diet plus 0.5 to 0.9 kg of cooked beef fat per day for 10 weeks. The dogs were instrumented for continuous monitoring of mean arterial pressure (MAP), heart rate, glomerular filtration rate (GFR), and effective renal plasma flow (RPF). The relative mRNA levels of 375 genes in renal cortex and medulla were determined simultaneously using cDNA membrane arrays (R&D Systems). RESULTS: The high fat diet increased body weight by 57% and MAP increased by 24 mm Hg (112 +/- 1 mm Hg vs. 88 +/- 3 mm Hg) in obese compared to lean dogs. In obese dogs, expression of 11 and 13 genes changed significantly (N= 4; P < 0.05) in the renal medulla and the cortex, respectively, relative to the lean dogs. Differences in renal gene expression profiles between lean and obese dogs were closely related to functional pathways, including those associated with sympathetic activation, inflammatory response, matrix formation, angiogenesis, endothelial dysfunction, attenuated actions of leptin, and attenuated cell survival. CONCLUSION: A high fat diet in dogs is associated with marked changes in renal gene expression profiles that provide potential molecular links to pathways associated with altered renal function and structure in obesity hypertension.

Animals↗
PubMed2004

Obesity and hypertension: two epidemics or one?

The association between obesity and hypertension is well documented, although the exact nature of this relation remains unclear. Sympathetic nervous and renin-angiotensin-aldosterone system activation appear to play an important role in the sodium and water retention, rightward shift in the pressure-natriuresis, and blood pressure elevation observed in obese individuals. Visceral obesity and the ectopic deposition of adipose tissue may be important in the activation of these systems and in the target organ damage that ensues. Weight loss is critical in the effective management of obesity hypertension and the accompanying target organ damage, although recidivism rates are high. However, prevention of weight gain should be the major priority for combating hypertension and its consequences in the future. The present review will provide an overview of our understanding of the etiology, pathophysiology, and treatment of obesity hypertension. Our focus is on the state of knowledge in humans. The potential role of abdominal obesity is considered throughout our review. We refer to relevant animal literature for supportive evidence and where little or no data in humans are available.

Animals↗
PubMed2004

The pioneering use of systems analysis to study cardiac output regulation.

This essay examines the historical significance of an APS classic paper that is freely available online: Guyton AC, Lindsey AW, and Kaufmann BN. Effect of mean circulatory filling pressure and other peripheral circulatory factors on cardiac output. Am J Physiol 180: 463-468, 1955 (http://ajplegacy.physiology.org/cgi/reprint/180/3/463).

Animals↗
PubMed2004

Pathophysiology and treatment of obesity hypertension.

Excess weight gain accounts for as much as 65-75% of the risk for essential hypertension and also greatly increases the risk for end stage renal disease (ESRD). Obesity raises blood pressure by increasing renal tubular reabsorption, impairing pressure natriuresis, and causing volume expansion due to activation of the sympathetic nervous system (SNS) and renin-angiotensin aldosterone system (RAAS), and by physical compression of the kidneys, especially when visceral obesity is present. The mechanisms of SNS activation in obesity are still unclear but may be due, in part, to hyperleptinemia that stimulates the hypothalamic pro-opiomelanocortin (POMC) pathway. With prolonged obesity, there may be a gradual loss of kidney function that worsens with time, exacerbates hypertension, and makes blood pressure more difficult to control. Lifestyle modifications, including weight reduction and increased physical activity, are essential first steps in the management of obesity hypertension and renal disease. Anti-obesity drugs offer potential pharmacotherapy for obesity hypertension, but current drugs are very limited and additional long-term studies are needed to test their safety and efficacy. Clinical trials are also needed to determine the most effective antihypertensive drugs for obese hypertensive patients. Special considerations for the obese patient, in addition to adequately controlling the blood pressure, include correcting the metabolic abnormalities and protecting the kidneys from further injury.

Animals↗
PubMed2003

Aldosterone antagonism attenuates obesity-induced hypertension and glomerular hyperfiltration.

This study examined the importance of aldosterone (ALDO) in mediating changes in renal function and increased mean arterial pressure (MAP) during the development of dietary-induced obesity in chronically instrumented dogs. Mean arterial pressure, heart rate (HR), and cardiac output (CO) were recorded 24 hours per day in lean dogs (n=7) before and after administration of an ALDO antagonist, eplerenone (EP) (10 mg/kg twice daily), for 10 days. After 10 days of EP treatment, the dogs (n=7) were given a supplement of cooked beef fat for 5 weeks while EP was continued. An untreated group (n=6) was fed a high fat diet for 5 weeks and used as control (C). In lean dogs, EP decreased MAP from 89+/-4 to 84+/-4 mm Hg and glomerular filtration rate from 67.4+/-6.8 to 53.2+/-4.9 mL/min while inducing a small negative Na+ balance (-42+/-12 mEq). Plasma renin activity increased from 0.4+/-0.1 to 2.7+/-0.7 ng AI/mL per hour and plasma K+ increased from 4.8+/-0.1 to 6.1+/-0.3 mEq/L. After 5 weeks of a high fat diet, body weight increased 45% to 53% in EP and C obese dogs. In C dogs, MAP increased by 16+/-3 mm Hg, compared with only 7+/-1 mm Hg in EPLE dogs. Compared with untreated dogs, the EP dogs had smaller increases in CO (18+/-4.6% versus 43+/-1.5%), HR (33+/-5% versus 60+/-3%), glomerular filtration rate (19+/-5% versus 38+/-6%), and cumulative Na+ balance (138+/-35 mEq versus 472+/-110 mEq) after 5 weeks of a high fat diet. Thus, EP markedly attenuated glomerular hyperfiltration, sodium retention, and hypertension associated with chronic dietary-induced obesity. These observations indicate that ALDO plays an important role in the pathogenesis of obesity hypertension.

Animals↗
PubMed2003

The kidney, hypertension, and obesity.

This paper provides a personal perspective of the role of abnormal renal-pressure natriuresis in the pathogenesis of hypertension. Direct support for a major role of renal-pressure natriuresis in long-term control of arterial pressure and sodium balance comes from studies demonstrating that (1) pressure natriuresis is impaired in all forms of chronic hypertension and (2) prevention of pressure natriuresis from operating, by servo-control of renal perfusion pressure, also prevents the maintenance of sodium balance hypertension. Although the precise mechanisms of impaired pressure natriuresis in essential hypertension have remained elusive, recent evidence suggests that obesity and overweight may play a major role. Obesity increases renal sodium reabsorption and impairs pressure natriuresis by activation of the renin-angiotensin and sympathetic nervous systems and by altered intrarenal physical forces. Chronic obesity also causes marked structural changes in the kidneys that eventually lead to a loss of nephron function, further increases in arterial pressure, and severe renal injury in some cases. Although there are many unanswered questions about the mechanisms of obesity hypertension and renal disease, this is one of the most promising areas for future research, especially in view of the growing, worldwide "epidemic" of obesity.

Blood Pressure↗
PubMed2003

Chronic cardiovascular and renal actions of leptin during hyperinsulinemia.

Hyperinsulinemia and hyperleptinemia occur concurrently in obese subjects, and both have been suggested to mediate increased blood pressure associated with excess weight gain. The goal of this study was to determine whether chronic hyperleptinemia exacerbates the effects of insulin on arterial pressure and renal function. Group I and II rats were infused with insulin (1.5 mU. kg(-1). min(-1)) for 21 days while maintaining euglycemia. After 7 days of insulin infusion, group II rats received leptin (1.0 microg. kg(-1). min(-1)) for 7 days, concomitant with insulin. Insulin plus glucose infusion reduced food intake to 55 +/- 7% of control, while leptin + insulin lowered food intake further to 22 +/- 4% of the initial control. Insulin initially raised mean arterial pressure (MAP) by 12 +/- 1 mmHg; then MAP declined to 5-8 mmHg above control during continued hyperinsulinemia. Leptin + insulin infusion increased MAP by 7 +/- 2 mmHg above the level observed in rats infused with insulin alone. Insulin raised heart rate (HR) by 17 +/- 5 beats/min, whereas leptin + insulin increased HR by 34 +/- 5 beats/min. Thus leptin appears to increase the effects of insulin to suppress appetite and to raise arterial pressure and HR.

Animals↗
PubMed2003

Impact of the obesity epidemic on hypertension and renal disease.

Excess weight gain is a major cause of increased blood pressure in most patients with essential hypertension, and also greatly increases the risk for renal disease. Obesity raises blood pressure by increasing renal tubular reabsorption, impairing pressure natriuresis, causing volume expansion due to activation of the sympathetic nervous system and renin-angiotensin system, and by physical compression of the kidneys, especially when visceral obesity is present. The mechanisms of sympathetic nervous system activation in obesity may be due, in part, to hyperleptinemia that stimulates the hypothalamic pro-opiomelanocortin pathway. With prolonged obesity, there may be a gradual loss of nephron function that worsens with time and exacerbates hypertension. Weight reduction is an essential first step in the management of obesity hypertension and renal disease. Special considerations for the obese patient, in addition to adequately controlling the blood pressure, include correction of the metabolic abnormalities and protection of the kidneys from further injury.

Animals↗
PubMed2003

Obesity-associated hypertension and kidney disease.

PURPOSE OF REVIEW: The worldwide prevalence of obesity and its associated metabolic and cardiovascular disorders has risen dramatically during the past two decades. Our objective is to review the mechanisms that link obesity with hypertension and altered kidney function. RECENT FINDINGS: Current evidence suggests that excess weight gain may be responsible for 65-75% of the risk for essential hypertension. Abnormal renal pressure natriuresis, due initially to increased renal tubular sodium reabsorption, is a key factor linking obesity with hypertension. Obesity increases renal sodium reabsorption by activating the renin-angiotensin and sympathetic nervous systems, and by altering intrarenal physical forces. Adipose tissue functions as an endocrine organ, secreting hormones/cytokines (e.g. leptin) that may activate the sympathetic nervous system and alter kidney function. Excess visceral adipose tissue may physically compress the kidneys, increasing intrarenal pressures and tubular reabsorption. Sustained obesity eventually causes structural changes in the kidneys and loss of nephron function, further increasing arterial pressure and leading to severe renal disease in some cases. SUMMARY: Despite considerable progress in understanding the pathophysiology of obesity, there are still no specific guidelines for the treatment of obesity hypertension other than weight reduction. Special considerations for obese hypertensive patients, in addition to controlling blood pressure, are correcting the metabolic abnormalities and protecting the kidneys from injury. This remains an important area for further research, especially in view of the current 'epidemic' of obesity in most industrialized countries.

Comorbidity↗
PubMed2003

How to review a paper.

Most scientists acquire their training in manuscript review not through instruction but by actually doing it. Formal training in manuscript analysis is rarely, if ever, provided. Editors usually choose reviewers because of expertise in a given subject area and availability. If an individual repeatedly submits bad reviews, it is likely that that person will not be asked to review a manuscript again. Being invited to review a manuscript is an honor, not only because you are being recognized for your eminence in a particular area of research but also because of the responsibility and service you provide to the journal and scientific community. The purpose of this article is to define how best to peer review an article. We will stipulate several principles of peer review and discuss some of the main elements of a good manuscript review, the basic responsibilities of a reviewer, and the rewards and responsibilities that accompany this process. Proper reviewer conduct is essential for making the peer review process valuable and the journal trustworthy.

Humans↗
PubMed2003

Historical perspective of the renin-angiotensin system.

Researchers continue to be fascinated with the renin-angiotensin system (RAS) more than 100 yr after its discovery because of its powerful role in controlling sodium balance, body fluid volumes, and arterial pressure. Development of drugs that block different components of this system has led to powerful treatments for hypertension, heart failure, diabetes, and other diseases. Molecular approaches to studying this system offer new possibilities for better understanding the physiology and pathophysiology of the RAS, and for developing new therapeutic paradigms. Our challenge in the future will be to effectively utilize the technological advances that are taking place in virtually all areas of science, including the RAS, and to translate them into a better understanding of the pathophysiology and treatment of human diseases.

Angiotensin-Converting Enzyme Inhibitors↗