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Biomedical subjects

S Julius

Publications and source records attributed to S Julius.

At least 91 records · Page 5Linked to original sources
PubMed1993

Contrasting effects of epinephrine on forearm hemodynamics and arterial plasma norepinephrine.

Circulating catecholamines are widely considered to cause vasoconstriction. However, in the present study an intravenous infusion of 0.01 micrograms/kg/min epinephrine for 10 min in healthy men (n = 40, 20 to 40 years of age), which raised arterial plasma epinephrine from 100 +/- 13 to 231 +/- 22 pg/mL (mean +/- SE), increased forearm blood flow (FBF) from 2.79 +/- 0.17 to 3.45 +/- 0.25 mL/100 forearm tissue/min (P < .001), and decreased forearm vascular resistance (FVR) from 37.0 +/- 2.4 to 31.1 +/- 2.1 (arbitrary units). Further stepwise increase in epinephrine infusion rate progressively raised FBF (to a maximum 6.91 +/- 0.46) and decreased FVR (to minimum 16.7 +/- 2.0), and increased arterial plasma norepinephrine by more than 60% (P < .001). Thus, circulating epinephrine in concentrations that can be produced by mental stress has, despite its ability to increase sympathetic drive, a regional vasodilating effect in the human forearm.

Adult↗
PubMed1993

Reflex sympathetic activation induces acute insulin resistance in the human forearm.

Inferences about the association between sympathetic overactivity and insulin resistance have been drawn from the infusion of sympathomimetic amines in supraphysiological doses. We used the isolated perfused human forearm to investigate the effect of reflex-induced sympathetic nervous system activation on the peripheral utilization of glucose in the skeletal muscles of 14 healthy men. Local hyperinsulinemia in the forearm (132 +/- 25 microunits/mL for 90 minutes) induced a significant increase in the utilization of glucose from baseline (16.4 +/- 3.1 mg.dL-1.min-1 per 100 mL forearm volume) to a plateau (85.7 +/- 15.1 mg.dL-1.min-1 per 100 mL forearm volume) between 40 and 60 minutes of insulin infusion but did not alter the utilization of oxygen. Reflex sympathetic nervous system activation was elicited by unloading of cardiopulmonary receptors with bilateral thigh cuff inflation to 40 mm Hg between 60 and 90 minutes of insulin infusion. Blood flow in the forearm was significantly decreased with inflation of thigh cuffs (average decrease of 19%, p < 0.0001). As a result of thigh cuff inflation, there was a reduction in the utilization of glucose (a decrease of 23%, p < 0.02), whereas oxygen utilization was unchanged. We find that an increase in sympathetic nervous system activation (within the normal range of physiological responses) can cause acute insulin resistance in the forearm of healthy volunteers. The reflex caused no change in oxygen utilization, but the same stimulus elicited a decrease in the utilization of glucose.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Evaluation of self-measured home vs. clinic intra-arterial blood pressure.

Home blood pressure (BP) monitoring is useful in the clinical management of patients with hypertension and the identification of those with "white-coat" hypertension; i.e. high readings in the clinic but normal BP at home. In the process of evaluating this technique, we compared self-measured home BP with intra-arterial BP. Healthy white men (n = 40) of 20-40 years of age and body weight below 95 kg were recruited by advertising in the local newspaper. Following a standardized procedure, performed within 2-4 weeks of a response to the advertisement, BP was measured by a physician at a clinic screening, by the subject at home (14 readings in 7 days) and finally in the clinic concomitantly intra-arterially and oscillometrically. The correlation coefficient for mean (M) home BP (r = 0.73) and oscillometric BP (r = 0.74) against intra-arterial BP were slightly higher than for screening BP (r = 0.65). However, in plots of the differences for individual MBP between the methods against the average of the methods, it appears that at levels of average MBP above 100 mmHg, screening BP overestimates the BP level, while this was not the case for home BP or oscillometric BP. Thus, by using intra-arterial measurement as standard of comparison, subject self-measured home BP is a reliable method of estimating blood pressure level in young men. Home BP measured shortly after screening and recruitment provides useful information of resting BP in subjects who potentially may have initial anxiety about BP measurement.

Adult↗
PubMed1992

Does blood pressure reduction necessarily compromise cardiac function or renal hemodynamics? Effects of the angiotensin-converting enzyme inhibitor quinapril.

Clinical studies indicate that the angiotensin-converting enzyme inhibitor quinapril is an effective antihypertensive agent when administered once daily. At the end of a 4-week, double-blind crossover trial comparing quinapril and placebo, patients were admitted for a hemodynamic profile study 12 hours after taking the previous dose. A final 20 mg dose of quinapril had no additional effect on blood pressure. This is interesting inasmuch as the plasma half-life of the active metabolite quinaprilat is approximately 2 hours and the effective accumulation half-life is approximately 3 hours. The blood pressure reduction in patients with mild hypertension receiving long-term quinapril therapy may be more closely related to prolonged angiotensin-converting enzyme inhibition or to an effect on tissue angiotensin II concentration than to the plasma half-life. This may be the case particularly for cardiac output and renal circulation, because quinapril lowers total vascular resistance without increasing cardiac output or disturbing autoregulation of renal blood flow. Reduced ventricular wall stress, improved diastolic function, and lower renal perfusion pressure may spare cardiac function and glomeruli from hypertensive vascular damage.

Adult↗
PubMed1992

Assessment of autonomic nervous function in human hypertension.

In spite of the popular belief that "nervous tension," "stress," and hypertension are causally related, it has been difficult to prove a role of autonomic dysfunction in the genesis of essential hypertension. There are three major reasons for this: 1) autonomic function cannot be assessed with one simple test, 2) the short-term "phasic" and long-term "tonic" autonomic control of blood pressure are not necessarily interrelated, and 3) hypertension is a dynamic process in the course of which there are changes in autonomic control. Some of the controversies in the field stem from the lack of appreciation of these limitations.

Autonomic Nervous System↗
PubMed1992

Effect of home blood pressure and gender on estimates of the familial aggregation of blood pressure. The Tecumseh Blood Pressure Study.

Blood pressure (BP) readings from a single clinic visit are often used in population studies investigating the genetic basis of BP. We examined first-degree relatives in the Tecumseh Blood Pressure study to compare heritability estimates of BP readings obtained in the clinic-office setting (the average of two seated readings) with self-reported home BP readings (the average of 14 readings) taken over a 1-week period. The hypothesis tested was that repeated BP readings obtained in the home over the 1-week period would have fewer artifacts (i.e., environmentally induced variability in BP) and thus would better estimate the true "basal" BP that, in turn, would improve heritability estimates. We and others assume that the true basal BP level is heritable. We therefore expected that this "true" BP, by reducing BP variability of offspring, would show a stronger between-sibling correlation and that it would correlate better to parental BP as measured in a clinic setting. Correlation coefficients were calculated between siblings in the present Tecumseh study using self-reported home BP and clinic BP readings. Among 380 siblings (average age, 31.4 years), correlation coefficients for the home readings were of the same magnitude as for office readings (home, r = 0.23, p less than 0.01; office, r = 0.24, p less than 0.01). When offspring clinic BP readings were compared with archived BP data on parents, the correlation between offspring clinic and parental clinic BP readings was stronger (r = 0.24, p less than 0.05) than the correlation of offspring home BP readings to parental clinic BP readings (r = 0.17, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

The interconnection between sympathetics, microcirculation, and insulin resistance in hypertension.

The pathophysiology of the frequent association of insulin resistance and hypertension has not been elucidated. The skeletal muscle is the major site of insulin resistance; when stimulated with insulin, the hypertensive skeletal muscles extract less glucose than the normotensive. We postulate that hypertension-related changes in the skeletal muscle microcirculation contribute to the impaired glucose uptake in hypertension. Vascular rarefaction in hypertension impairs the delivery of insulin and glucose to muscle cells. Insulin resistance has been described both in human and experimental hypertension and both conditions are associated with vascular rarefaction. Functional studies (response to whole body or forearm exercise) and anatomic investigations (conjunctival photography, mesenteric and muscle biopsies) show vascular rarefaction in human hypertension. In addition, patients with hypertension are known to have a larger proportion of insulin resistant, poorly vascularized fast twitch muscle fibers. A few interventions can increase or decrease insulin resistance and these effects can be explained on hemodynamic grounds. Beta adrenergic blocking agents aggravate insulin resistance, and their main hemodynamic effect is a decrease of cardiac output. Converting enzyme inhibitors, alpha adrenergic blocking agents and possibly calcium antagonists decrease the insulin resistance, and their major hemodynamic effect is vasodilation. Physical training decreases insulin resistance; a higher capillary density in skeletal muscles is the hallmark of physical training. A hypothesis ought to rest on sufficient supporting data and its validity ought to lend itself to experimental verification. We believe our hypothesis meets both criteria. After outlining the supporting evidence we propose a number of tests to prove or disprove the hypothesis. In addition to the testable hypothesis we also speculate on the possible cause of the frequent association between hypertension and insulin resistance. We propose that both insulin resistance and blood pressure elevation represent a facet of the "defense reaction" which might have offered an early survival advantage and may, over evolutionary times, have fostered natural selection of subjects with both conditions.

Animals↗
PubMed1992

Correlates of the estimated arterial compliance in the population of Tecumseh, Michigan.

An estimate of arterial compliance--the stroke volume/pulse pressure ratio (SV/PP)--was studied in 801 participants in the Tecumseh Blood Pressure Study, a population-based ongoing cardiovascular, epidemiological investigation. The subjects were normal young adults (mean age 30 +/- 5.6 years) and 373 were females. Cardiac anatomy and function were studied by echo-Doppler methods, blood pressure being measured at the same time by the indirect method. The distribution of the SV/PP ratio was skewed toward higher values in larger subjects. After statistical adjustments for body surface area, this estimate of arterial compliance was found to be higher in females (2.00 +/- 0.62) than in males (1.90 +/- 0.58) (p < 0.05). When subjects were divided into tertiles, the group with the lowest estimated arterial compliance was normotensive but had higher systolic pressure, lower diastolic pressure, a similar mean arterial pressure, higher heart rate and higher left ventricular wall thickness ratio compared to subjects with higher arterial compliance. Indices of systolic ejection decreased and diastolic function was altered in the low compliance subjects. In addition, low compliance subjects also had higher fasting insulin levels. These findings suggest that the low arterial compliance in an otherwise normal population has negative cardiovascular correlates. The early association of decreased arterial compliance with anatomic, functional and biochemical aberrations suggests that estimates of arterial compliance might prove useful for prediction of cardiovascular complications.

Adolescent↗
PubMed1992

White coat hypertension: a follow-up.

Home blood pressure readings by self-monitoring (14 readings in 7 days) have been compared to readings taken in the clinic in 937 participants of the Tecumseh Blood Pressure Study. In the absence of firm criteria "hypertension at home" was defined as having home readings in the upper decile of the whole population. If a clinic reading exceeded 140 and/or 90 mmHg a subject was categorized as having clinic "hypertension". Two hypertensive groups emerged; one with both clinic and home hypertension ("sustained" N = 47) and one with high clinic but normal home blood pressure ("white coat" N = 50). Groups with "white coat" and "sustained" hypertension were very similar. Both groups were overweight, had faster heart rates, elevated cholesterol, insulin, triglyceride and decreased HDL levels. Blood pressure readings at previous exams (age 5, 8, 21 and 22) were elevated in both the "sustained" and white coat hypertension group compared to the normotensive controls. Subjects with white coat hypertension were not hyperresponders to the stress of mental arrythmetrics or to isometric exercise. The white coat hypertensives did not show abnormal anger, excessive submissiveness, or anxiety. The pathophysiology of the reproducible elevation of the clinic blood pressure in the white coat hypertensives remains unclear. Because of a higher risk of coronary heart disease and a risk for late development of sustained hypertension, subjects with white coat hypertension should be counselled on nonpharmacologic methods to control the blood pressure elevation and to ameliorate coronary risk factors.

Adolescent↗
PubMed1992

Early association of sympathetic overactivity, hypertension, insulin resistance, and coronary risk.

Whereas this review is based on the available evidence, interpretation of the data is entirely hypothetical and subjective. To a large degree the review reflects our long-standing fascination with the role of the sympathetic overactivity in hypertension. The basic tenet is that sympathetic overactivity in hypertension may lead to a number of secondary changes, all of which are conductive to coronary heart disease. We also propose that insulin resistance and hypertension are associated through an underlying hemodynamic abnormality and again find good evidence for a possible role of sympathetics in the genesis of such hemodynamic changes. Future research in our laboratory will be oriented toward experimental testing of various aspects of the proposed sympathetic overactivity/hypertension/insulin resistance hypothesis.

Antihypertensive Agents↗
PubMed1991

Autonomic nervous system dysregulation in human hypertension.

An increased sympathetic drive combined with decreased parasympathetic inhibition is found in patients with borderline hypertension, who characteristically have rapid heart rates, high cardiac output and relatively normal vascular resistance (hyperkinetic state). In established hypertension, cardiac output is normal, vascular resistance is elevated and signs of increased sympathetic drive are absent. Apparently hemodynamics and sympathetic drive change during hypertension. The mechanism of the hemodynamic transition in the course of hypertension is well understood. Cardiac output returns from elevated to normal values as beta-adrenergic receptors down-regulate and stroke volume decreases (due to decreased cardiac compliance). The high blood pressure induces vascular hypertrophy, which in turn leads to increased vascular resistance. The mechanism of the change of sympathetic tone from elevated in borderline hypertension to apparently normal in established hypertension can best be explained within the conceptual framework of the "blood-pressure-seeking" properties of the brain. In hypertension, the central nervous system seeks to maintain systemic blood pressure at the higher level. As hypertension advances and vascular hypertrophy develops, arterioles become hyperresponsive to vasoconstriction. At this point, less sympathetic drive is needed to maintain pressure-elevating vasoconstriction, and the central sympathetic drive is down-regulated. The etiology of increased sympathetic drive in hypertension remains unresolved. Subjects with increased sympathetic drive are also usually overweight and have elevated levels of insulin, cholesterol and triglycerides, as well as decreased high-density lipoproteins. Future research must focus on the link between coronary risk factors and sympathetic overactivity in hypertension.

Humans↗
PubMed1991

Changes in left ventricular diastolic filling during the development of left ventricular hypertrophy: observations using Doppler echocardiography in a unique canine model.

To examine changes in diastolic left ventricular filling during the development of left ventricular hypertrophy, serial pulsed Doppler echocardiographic studies were performed in a canine model of left ventricular hypertrophy induced by neurogenic pressor episodes. This model is unique since left ventricular hypertrophy develops without sustained hypertension. The neurogenic pressor episodes produced progressive increases in left ventricular mass of 17% by 3 weeks (p less than 0.03) and 23% by 9 weeks (p less than 0.001). During the course of hypertrophy development, there were no changes in resting heart rate, blood pressure, left ventricular volumes or ejection fraction, or end-systolic wall stress. However, peak early filling (peak E) velocity decreased from 65 +/- 5 cm/sec to 53 +/- 4 cm/sec by 3 weeks (p less than 0.05) and remained depressed at 9 weeks. In addition, peak E/A (the ratio of early to late peak filling) decreased by 3 weeks (p less than 0.01) and the contribution of atrial filling to total left ventricular diastolic filling increased by 9 weeks (p less than 0.005). There were significant correlations between the changes in left ventricular mass and the change in peak E velocity at 3 weeks (r = -0.92, p less than 0.001) but not at 9 weeks. These data indicate that left ventricular filling abnormalities occur early in the course of the development of left ventricular hypertrophy, are not a result of loading alterations related to sustained hypertension, and do not change significantly following increasing stages of hypertrophy.

Animals↗
PubMed1991

Clinical implications of pathophysiologic changes in the midlife hypertensive patient.

Both aging and hypertension decrease cardiac output through a lower stroke volume and a diminished beta-adrenergic responsiveness. In parallel, the vascular resistance increases because of vascular hypertrophy. In addition, in hypertension the alpha-adrenergic responsiveness is enhanced. Aging and hypertension are also associated with an increase in plasma cholesterol and insulin values. These alterations in cholesterol and insulin levels become particularly pronounced in middle-aged patients with hypertension. alpha-Adrenergic-blocking agents have a positive effect on lipids and insulin resistance. The shift toward enhanced alpha-adrenergic responsiveness, and the fact that vasodilators do not diminish exercise performance favor the use of alpha-blockers as a first drug in middle-aged patients with hypertension. Blood pressure lowering still remains the paramount goal, and these compounds should be used only if proved to be efficacious in a given individual patient.

Adrenergic alpha-Antagonists↗
PubMed1991

Predictors of blood pressure and hypertension. General principles.

Early intervention in the treatment of hypertension can reduce the detrimental effects of high blood pressure. Therefore it is important to be able to predict the development of hypertension in individuals. A number of factors can be used as predictors of hypertension, but only childhood high blood pressure (especially in combination with obesity) is a potent predictor of future hypertension. A family history of hypertension is a contributory risk factor, as is tachycardia, but neither is as strong a predictor as a youthful elevated pressure.

Adolescent↗
PubMed1991

Hyperkinetic borderline hypertension in Tecumseh, Michigan.

Of 691 healthy (untreated) villagers of Tecumseh, Michigan (average age 32.6 years), 99 had a clinical blood pressure exceeding 140/90 mmHg. Thirty-seven per cent of these borderline hypertensives had increased heart rate, cardiac index, forearm blood flow and plasma norepinephrine. These subjects had elevated self-determined home blood pressure (average of 14 measurements). The present hyperkinetic borderlines had elevated blood pressure at 5, 8, 21 and 23 years of age and their parents also had higher blood pressure. The prevalence of high blood pressure in Tecumseh, its long history, elevated blood pressure readings outside the physician's office and family background of hypertension, suggests that the hyperkinetic state is a significant clinical condition. Previous studies on hospital-based populations proved that the hyperkinetic state is caused by an excessive autonomic drive. The association of the hyperkinetic state with elevated norepinephrine in this study suggests that a sympathetic hyperactivity is present in a large proportion of unselected subjects with mild blood pressure elevation.

Adult↗