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Biomedical subjects

T G Coleman

Publications and source records attributed to T G Coleman.

At least 19 recordsLinked to original sources
PubMed1992

Development of hypertension in animals with reduced total peripheral resistance.

The object of the present study was to determine whether deoxycorticosterone acetate (DOCA)-salt hypertension can be produced in rats in the presence of low total peripheral resistance (TPR) induced by long-term administration of minoxidil, a vasodilator. The rats were divided into four groups: sham-control, DOCA-salt, minoxidil, and DOCA-salt with minoxidil. The rats in both DOCA groups had DOCA pellets implanted subcutaneously and were given saline to drink. The rats in both minoxidil groups were given minoxidil (3 mg/day) in the drinking water throughout the experiment. Final measurements, including mean arterial blood pressure, cardiac index, and renal blood flow were made after 4-6 weeks. Flow measurements were made using radioactive microspheres. Cardiac index (ml.min-1.100 g-1) in sham-control rats averaged 18 +/- 2 and was higher in the other groups: 23 +/- 4 (DOCA-salt), 25 +/- 2 (minoxidil), and 30 +/- 2 (DOCA-salt plus minoxidil). Mean arterial pressure (mm Hg) was increased in both DOCA-salt rats (160 +/- 8) and DOCA-salt plus minoxidil rats (153 +/- 5) as compared with sham-control (116 +/- 2) and minoxidil (113 +/- 3) rats. There was no significant difference in TPR between the sham-control and DOCA-salt rats, but TPR in minoxidil and DOCA-salt plus minoxidil rats was 30% and 28% lower than that in untreated sham-control and DOCA-salt hypertensive rats, respectively. In contrast, renal vascular resistance was significantly increased in both DOCA-salt groups as compared with non-DOCA-salt groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Chronic hyperinsulinemia and blood pressure regulation.

The aims of this study were to determine whether chronic hyperinsulinemia, comparable to that found in obese hypertensives, elevates mean arterial pressure (MAP) or potentiates the hypertensive effects of angiotensin II (ANG II). Studies were conducted in conscious dogs with kidney mass reduced by 70% in order to increase their susceptibility to hypertensive stimuli. Insulin infusion (0.5 or 1.0 mU.kg-1.min-1 iv) for 7 days with plasma glucose held constant raised plasma insulin more than fivefold but did not increase MAP in four dogs on 138 meq/day Na intake. In seven dogs maintained on a high Na intake (319 meq/day), insulin infusion (1.0 mU.kg-1.min-1) for 28 days raised fasting insulin from 9.8 +/- 1.5 to 56-78 microU/ml but did not increase MAP, which averaged 106 +/- 2 mmHg during control and 102 +/- 2 mmHg during 28 days of insulin infusion. Insulin caused transient sodium and potassium retention followed by renal "escape" that was associated with increased glomerular filtration rate (12-27%). Plasma renin activity and plasma aldosterone were not altered by insulin. In five dogs infused with ANG II (2.0 ng.kg-1.min-1) to cause mild hypertension, insulin infusion (1.0 mU.kg-1.min-1) for 6-28 days did not increase MAP further. Thus chronic hyperinsulinemia did not elevate MAP, even when kidney mass was reduced, and did not potentiate the hypertensive effects of ANG II. These findings suggest that additional factors besides hyperinsulinemia per se are responsible for obesity-associated hypertension.

Angiotensin II↗
PubMed1989

A simulation support system for solving large physiological models on microcomputers.

Although physiological modeling and computer simulation have become useful research tools to test new scientific theories and to design and analyze laboratory experiments, developing a new model can be a tedious process because the investigator must often write very complex and specific routines for data input and output. To facilitate the design of new models (as well as the use of existing models), we have developed MODSIM, a FORTRAN-based simulation support system for the IBM PC computer than can accommodate very large dynamic models having up to several thousand equations. It provides the investigator with utilities for continuous on-line graphical and/or tabular output, as well as facilities for dynamic interaction with the model. The user must only supply a model as a list of mathematical equations written in FORTRAN, along with the initial values of the model variables and parameters. The model is precompiled, compiled, and then linked to the MODSIM utilities. Without further programming, the user can then solve the model, select variables for graphical output, and stop the model at any time to analyze the data or to change a parameter before resuming the simulation. This simulation system makes it very easy to develop new models that actively interact with the experimental research of the investigator.

Computer Simulation↗
PubMed1989

Does chronic hyperinsulinemia cause hypertension?

The aim of this study was to determine whether chronic hyperinsulinemia, comparable to that found in obesity-associated hypertension, causes sustained increases in mean arterial pressure (MAP) or potentiates the hypertensive effects of angiotensin II (ANG II). Insulin infusion (0.5 or 1.0 mU/kg/min, IV), with plasma glucose held constant by IV glucose infusion, for seven to 28 days raised plasma insulin by five- to ten-fold, but did not significantly change MAP in dogs with reduced kidney mass that were maintained on high sodium intake. In dogs infused with ANG II to cause mild hypertension, insulin for 28 days did not potentiate the hypertension. Insulin infusion did, however, cause modest sodium retention during the first few days of infusion. These findings suggest that additional factors besides hyperinsulinemia per se are responsible for obesity-associated hypertension.

Angiotensin II↗
PubMed1989

The renin-angiotensin system. Normal physiology and changes in older hypertensives.

The long-term effects of angiotensin (ANGII) on arterial pressure regulation appear to be closely linked to volume homeostasis, via the renal-pressure natriuresis mechanism, both in normal humans and in older hypertensives. In response to disturbances such as increased sodium intake, suppression of ANGII and aldosterone formation greatly amplifies the effectiveness of the pressure natriuresis mechanism, thereby preventing large increases in body fluid volumes and minimizing the rise in blood pressure needed to maintain sodium balance. When ANGII levels are inappropriately elevated, the antinatriuretic effects of ANGII cause increased arterial pressure, which then serves to maintain sodium and water balance via the pressure natriuresis mechanism. The primary intrarenal and extrarenal mechanisms by which ANGII controls renal excretion and arterial pressure include: (1) a direct effect of ANGII on tubular sodium transport; (2) a preferential constrictor action of ANGII on efferent arterioles, which increases sodium reabsorption by altering peritubular capillary physical forces (efferent arteriolar constriction also prevents excessive decreases in glomerular filtration rate when renal perfusion is compromised, such as in renal artery stenosis); and (3) extrarenal effects of ANGII, including stimulation of aldosterone secretion. Current evidence suggests that the direct effects of ANGII on the kidney are quantitatively more important than indirect effects mediated by aldosterone. In older hypertensives, plasma renin activity and aldosterone concentration are often suppressed, perhaps due to loss of functional nephrons and increased sodium chloride delivery to the macula densa of the remaining nephrons.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1988

Residual effects of ether anesthesia on whole-body hemodynamics and organ blood flows in the rat.

This study was designed to determine the short-term residual effects of ether anesthesia on hemodynamics and blood flow distribution in the rat. Eighteen male Sprague Dawley rats were instrumented and allowed to recover for at least 2 days before beginning the experiment. Using microspheres, cardiac output, and blood flow distribution were determined at five different periods: before ether anesthesia; at a surgical level of ether anesthesia; and 20 min, 1 hr, or 3 hr after cessation of anesthesia. Ether anesthesia initially decreased arterial pressure, increased cardiac index, and decreased total peripheral resistance. The residual effects of ether included progressive increases in arterial blood pressure and an increase in total peripheral resistance index. Cardiac index was returned to normal 1 hr after termination of anesthesia. Blood flow to the brain and heart increased during anesthesia and was significantly elevated 1 hr later. Other organs, including kidney, spleen, and intestine showed a decrease in blood flow during anesthesia, which persisted for at least 20 min. Thus, ether anesthesia produced acute and residual disturbances in hemodynamics and blood flow distribution, which may have an untoward influence on concomitant experimental observations.

Anesthesia, Inhalation↗
PubMed1987

Hemodynamic monitoring for 24 h in unanesthetized rats.

A new technique is described that allows minute-to-minute recordings of cardiac output and arterial pressure in unanesthetized rats for periods of 24 h and longer. Rats were instrumented with electromagnetic flow probes and arterial catheters. An electrical and hydraulic swivel was interposed between the rat and recording apparatus to allow free range of movement. Data were collected and analyzed once each minute by computer. Average 24-h values (mean +/- SD) for the following hemodynamic variables were determined in eight rats [expressed where appropriate as a function of body weight (BW)]: cardiac output (98.1 +/- 14.7 ml/min), cardiac index (29.2 +/- 4.4 ml.min-1.100 g BW-1), mean arterial pressure (92.5 +/- 7.8 mmHg), heart rate (347 +/- 45 beats/min), peak aortic flow (403 +/- 32 ml/min), stroke volume (282 +/- 26 microliters), stroke volume index (84.4 +/- 8.1 microliters/100 g BW), and total peripheral resistance index (3.26 +/- 0.46 mmHg.ml-1.min.100 g BW). These results provide a data base of hemodynamic values for unanesthetized adult, Sprague-Dawley male rats, which has not been previously available. In addition, cardiac index, mean arterial pressure, and total peripheral resistance index demonstrated diurnal variation. Diurnal variation contributed substantially to the overall variance observed within these variables. Hourly variance was also substantial and indicates the use of continuous recordings for short-term experiments.

Animals↗
PubMed1987

Overall hemodynamic pattern in coarctation of the abdominal aorta in conscious rats.

This study was designed to examine the total body hemodynamics of abdominal aortic coarctation hypertension. The study quantitates both regional and organ blood flow and resistance in conscious rats both above and below an experimentally produced coarctation. The experimental group consisted of 10 male Sprague-Dawley rats with a mean pressure gradient of 68 mm Hg across the coarctation. This experimental group was compared with a group of eight control rats with no pressure gradient. Flow measurements were made with radioactively labeled microspheres 4 weeks after aortic constriction. This aortic coarctation produced an increase in cardiac index (22%) and total peripheral resistance (19%). Blood flow through tissues proximal to the coarctation was not different from control; vascular resistance was increased (31%). Flow through the tissues distal to the coarctation was increased (16%); vascular resistance was decreased (-22%). The upper carcass, diaphragm, and brain were the tissues most representative of flow above the coarctation, and the lower carcass and large intestine were the tissues most representative of flow below the coarctation. Coarctation of the aorta produced cardiac hypertrophy and increased microsphere shunting to the lungs.

Animals↗
PubMed1986

Regulation of arterial pressure: role of pressure natriuresis and diuresis.

The importance of the renal pressure natriuresis and diuresis mechanisms in long-term control of body fluid volumes and arterial pressure has been controversial and difficult to quantitate experimentally. Recent studies, however, have demonstrated that in several forms of chronic hypertension caused by aldosterone, angiotensin II (AngII), vasopressin, or norepinephrine and adrenocorticotropin, increased renal arterial pressure is essential for maintaining normal excretion of sodium and water in the face of reduced renal excretory capability. When renal arterial pressure was servo-controlled in these models of hypertension, sodium and water retention continued unabated, causing ascites, pulmonary edema, or even complete circulatory collapse within a few days. Apparently, other mechanisms for volume homeostasis, such as the various natriuretic and diuretic factors that have been postulated, are not sufficiently powerful to maintain fluid balance in the absence of increased renal arterial pressure when renal excretory function is reduced in these forms of hypertension. The intrarenal mechanisms responsible for pressure natriuresis and diuresis are not entirely clear, but they seem to involve small increases in glomerular filtration rate and filtered load as well as reductions in fractional reabsorption in proximal and distal tubules. During chronic disturbances of arterial pressure additional factors, especially changes in AngII and aldosterone formation, act to amplify the effectiveness of the basic renal pressure natriuresis and diuresis mechanisms in regulating arterial pressure and body fluid volumes.

Aldosterone↗
PubMed1985

Two hemodynamic problems commonly associated with the microsphere technique for measuring regional blood flow in rats.

The purpose of this study was to reevaluate two major steps associated with the radioactive microsphere technique in rats; the hemodynamic effects of the solutions used to inject the microspheres, and the hemodynamic effects of repeated blood withdrawals. With regard to the first, Flaim et al. (1978) have shown that 1.0 ml of 10% dextran injected into the rat may result in a severe pressure drop. The present study showed that even 0.1 ml of 10% dextran caused significant hypotension 46% of the time. Six other mediums were also tested as possible suspending media. It was concluded that a dextrose solution (sp gr 1.3) was the best microsphere injection medium based on the length of time the microspheres stayed mixed in the solution and the minimal hemodynamic alterations caused during injection. With regard to the second concern, cardiac output decreased approximately 7% with each reference sample withdrawal. When volume was replaced with a Ficoll-70 solution, cardiac output decreased less than 3%. These data show that repeated blood withdrawals are possible as long as the volume of blood is replaced. Thus, several isotopes can be injected in the same rat to allow measurement of regional blood flow under different experimental conditions.

Animals↗
PubMed1979

Whole body response of the peripheral circulation following hemorrhage in the rat.

Changes in mean circulatory filling pressure (MCFP) after hemorrhage reflect the whole-body response of the peripheral circulation to restore the driving force for venous return. In this study, changes in MCFP were measured for 15 min following a rapid 8 ml/kg hemorrhage. Three groups of rats were studied: 1) conscious, untreated; 2) conscious, ganglion blocked; and 3) pentobarbital anesthetized. In all three groups, hemorrhage decreased MCFP approximately 2.6 mmHg immediately after hemorrhage. In the conscious untreated rat, MCFP recovered 1.3 mmHg in 15 min; 83% of this recovery was complete within 2 min, and over 50% was complete by 30 s posthemorrhage. With ganglionic blockade, recovery was slowed to about 70% of that in the conscious, untreated animal during the first 5 min after hemorrhage. MCFP recovery was substantially depressed by pentobarbital, averaging only 42% of that in the untreated animal 5 min after hemorrhage. The results demonstrate that peripheral changes can quickly restore nearly 50% of the MCFP decrease occurring immediately after mild hemorrhage and that about one-third of this response is mediated by the sympathetic nervous system. Pentobarbital anesthesia greatly inhibits recovery, although its repressive mechanism is not known.

Animals↗
PubMed1979

Hypertension in dogs during antidiuretic hormone and hypotonic saline infusion.

Experimental hypertension was produced in 7 dogs by continuously infusing suppressor amounts of antidiuretic hormone (ADH) and hypotonic saline after renal mass had been surgically reduced to 30% of normal. Data were collected during 9 days of control measurements, 14 days of ADH and saline infusion, and then 3 days of saline infusion to 1) determine the chronic effects of ADH on arterial pressure and 2) determine whether hypertension could be maintained during hyponatremia. During the period of ADH infusion, arterial pressure increased to hypertensive levels while plasma sodium concentration decreased almost 20 meq/1. Also, during the ADH infusion period, the dogs demonstrated decreases in heart rate, plasm potassium concentration, plasma renin activity, and plasma aldosterone concentration. Fluid volume expansion was evidenced by sustained increases in blood volume and sodium space. We conclude that when renal function is compromised, subpressor amounts of ADH can contribute to the development of hypertension, probably due to its fluid-retaining properties and in spite of the attendant hyponatremia.

Animals↗
PubMed1979

Essential role of mean circulatory filling pressure in salt-induced hypertension.

Experimental hypertension was produced in nine dogs by continuously infusing isotonic saline after renal mass had been surgically reduced to approximately 30% normal. Data were collected during 8 days of base-line measurements and 13 days of saline infusion to determine the cause of the initial increase in cardiac output observed in this type of hypertension and to measure other variables possibly important in the pathogenesis of hypertension. During the infusion period, these dogs demonstrated an increase in arterial pressure to hypertensive levels, transient increases in blood volume, sodium space, and cardiac output, initially depressed then subsequently elevated total peripheral resistance, and decreases in plasma renin activity and plasma aldosterone concentration. The mean circulatory filling pressure increased 4.7 Torr by day 3 and was still elevated 2 Torr at the end of the 2nd wk of infusion. We conclude that the initial increase in cardiac output in salt-loading hypertension is due to elevated fluid volumes and the associated increase in mean circulatory filling pressure.

Aldosterone↗