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Biomedical subjects

T G Coleman

Publications and source records attributed to T G Coleman.

At least 55 records · Page 3Linked to original sources
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↗
PubMed1979

Chronic blockade of angiotensin II formation during sodium deprivation.

The present study was designed to investigate the mechanisms by which the renin-angiotensin system (RAS) regulates arterial pressure (AP) and renal function during chronic sodium deprivation. Intravenous infusion of the converting enzyme inhibitor SQ 14225 (14 microgram.kg-1.mm-1) for 8 days in 12 sodium-deficient dogs caused a marked decrease in AP from 90 +/- 1 to 67 +/- 2 mmHg and a reduction in glomerular filtration rate (GFR), filtration fraction (FF), and plasma aldosterone concentration (PAC). Despite the fall in AP and GFR, urinary Na excretion and effective renal plasma flow (ERPF) increased above control levels. In four dogs, infusion of aldosterone (200 micrograms/day) for 8 days during continuous SQ 14225 infusion restored PAC to levels above control, but did not significantly change AP or renal function from the values observed during SQ 14225 infusion alone. However, infusion of angiotensin II (AII) (10 or 20 ng.kg-1.min-1) for 5--8 days during continuous SQ 14225 infusion almost completely restored AP and renal function to control levels. These data indicate that the RAS plays a major role in regulating AP, renal hemodynamics, and Na excretion during Na deprivation, probably through the direct effects of AII rather than through changes in PAC.

Aldosterone↗
PubMed1979

A mathematical model of the human body in health, disease, and during treatment.

This paper presents a preliminary description of a mathematical model of the human body and some details of the computer software and hardware used to study the model. The model includes many organ systems of the body and the interplay among systems. In addition to this physiological framework, a variety of diseases and therapeutic measures can be simulated. The model can be used in two different ways. In one mode, hypothetical experiments can be conducted that focus on the underlying physiological mechanisms and the complex interaction among organ systems that are essential to the maintenance of life. In a second mode, clinical encounters can be simulated in which hypothetical patients are seen, diagnosed and treated.

Acid-Base Equilibrium↗
PubMed1979

A restraining cage for instrumented rats.

A rectangular restraining cage for chronically instrumented rats was constructed of acrylic plastic. The cage allowed connections between implanted instrumentation and external recorders through a slot in the top cover. The cage was easy to load and unload through a removable cover plate, and the sidewall was adjustable to accommodate rats of diverse sizes. The cage was easy to dissemble for cleaning, and it was inexpensive.

Animals↗
PubMed1978

Subpressor angiotensin infusion, renal sodium handling, and salt-induced hypertension in the dog.

We studied the combined effect of subpressor amounts of angiotensin and long-term sodium chloride infusion on arterial pressure in 16 dogs for periods of 2--8 weeks. In dogs receiving 3.5 liters of isotonic NaCl daily, but no angiotensin, the arterial pressure increased an average of only 3 mm Hg. When angiotensin was infused continuously at a rate of 5 ng/kg per min (a rate too small to cause an observable immediate increase in pressure, subsequent infusion of 3.5 liters of saline daily then increased the pressure by 39 mm Hg. The urinary output of sodium increased to the same extent in both instances, that is, there was no extra sodium loss because of the elevated pressure. This suggests that the angiotensin significantly blocked the normal "pressure natriuresis" usually seen with such large increases in pressure. However, the plasma aldosterone levels during angiotensin infusion were not found to be different from those in the absence of angiotensin. Therefore, we have suggested that the tendency of the kidneys to retain sodium under the influence of angiotensin was probably caused mainly by a direct effect of angiotensin on the kidney itself. Such a direct renal sodium-retaining effect also could be a contributing factor in the marked hypertension that results from salt administration in the presence of small amounts of angiotensin.

Aldosterone↗
PubMed1977

Angiotensin II antagonists in dehydrated rabbits without baroreceptor reflexes.

Blood pressure effects of angiotensin II antagonists were studied in sham-operated and baroreceptor-denervated rabbits in the normal water-replete state or after 6 days of water deprivation (dehydrated). Experiments were performed in awake rabbits. Dehydrated rabbits had significantly higher plasma sodium concentrations, hematocrits, and plasma renin activities, but lower plasma potassium concentrations and body weights than water-replete rabbits. Administration of angiotensin II antagonists caused a significant decrease in mean arterial pressure in dehydrated rabbits (-16 mmHg in sham-dehydrated and -19 mmHg in denervated-dehydrated) but not in water-replete ones, whether the baroreceptor reflexes were intact or not (-1 mmHg in sham replete and -4 mmHg in denervated replete). The open-loop feedback gain of the renin-angiotensin system in blood pressure control was calculated as -1.6. The results demonstrate an important role of angiotensin II in blood pressure regulation during the high-renin, dehydrated state, but not during the normal renin, water-replete state. Abolishment of baroreceptor reflexes did not unmask an important role of normal levels of angiotensin II in blood pressure regulation.

Angiotensin II↗
PubMed1977

Feedback mechanisms of arterial pressure control.

Arterial blood pressure varies very little among human beings and most other mammals for that matter. This suggests that a powerful control scheme is at work; it becomes more apparent when we break the various feedback loops and observe the excursions of blood pressure in the absence of any control. Two important control loops are found in the baroreceptor reflexes operating over the short term and the kidneys operating over the long term. The aortic and carotid baroreceptors stabilize pressure, preventing short-term fluctuations; when this control loop is surgically removed, lability increases with little change in the average pressure. Over the long term, the kidneys determine the average level of arterial pressure; when they are removed, pressure slowly drifts up and down as fluid is inadvertently accumulated or lost. There are several possible connections between the function of the kidneys and arterial pressure, including the release of vasoactive endocrines by the kidney and the adjustment of body fluids via salt and water excretion. Because salt excretion and water excretion often change in parallel, it has been difficult to identify the individual importances of each. However, we found that increasing the sodium stores of the body while holding volume constant does not produce hypertension, expanding fluid volume while maintaining or actually decreasing sodium concentration does lead to hypertension. Hence, when the kidneys are normal, long-term stability results from this loop: fluid volumes alter arterial pressure; pressure alters renal excretion; excretion alters fluid volumes.

Animals↗
PubMed1976

Integration and control of circulatory function.

In this chapter we have emphasized especially the intrinsic controls of the circulation, such as the autoregulation mechanism for control of local blood flow, automatic control of cardiac output, long-term control of arterial pressure, long-term control of blood volume, and automatic distribution of fluids between the circulation and the interstitial spaces. The reasons for emphasizing these mechanisms are several: first, many experiments have now shown that the intrinsic mechanisms can provide highly stable long-term control of the circulation. Second, the value of the nervous and hormonal controls have probably been greatly overemphasized in the past. And, third, there are special complexities of the intrinsic controls--such as nonlinearities, delay in responses, and other effects--that have made these difficult to understand; it is probably these difficulties that have led to their underemphasis. However, we have not meant to take from the nervous and hormonal systems their true importance in circulatory control. For instance, intrinsic mechanisms have almost no capability for acute arterial pressure control (only for long-term control), and they have no mechanism for providing the drive necessary to make the animal ingest water and electrolytes. These require the nervous controls. Also, nervous reflexes are important in enhancing the effectiveness of blood volume control and control of cardiac pumping. Among the hormonal mechanisms, the renin-angiotensin system can provide a modest degree of arterial pressure control when the pressure falls below normal by eliciting a vasoconstrictor response in the peripheral blood vessels. However, this system seems to have an even more important renal function, a direct effect on kidneys to cause fluid retention; this in turn increases the body fluid volume and in this way increases the arterial pressure. Finally, the roles of ADH and aldosterone in the control of blood volume have probably been greatly overemphasized. On the other hand, both clinical experience and experimental studies are beginning to demonstrate that the thirst/ADH system is probably by far the most potent mechanism that we have for control of extracellular fluid sodium ion concentration. On the other hand, the aldosterone mechanism seems to be our primary control system for maintaining a normal extracellular fluid concentration of potassium.

Angiotensin II↗
PubMed1975

The role of the kidney in spontaneous hypertension.

There is direct and indirect evidence that the kidneys are involved in the onset of hypertension in spontaneously hypertensive animals. In the Dahl strain, rather convincing evidence exists for a primary, inherent renal defect that is worsened by high dietary salt. In the Okamoto and New Zealand strains, an intrinsic defect may be provoked by increased sympathetic nerve activity. Similarities between all of these strains and Goldblatt hypertension suggest a fluid volume abnormality, but the gradual onset of elevated pressure and continuing growth during development of hypertension may obscure critical volume changes. Theoretically, arterial pressure, somewhat independent of intermediate steps, will reach the level which is dictated by renal function as being necessary for the maintenance of salt and water homeostasis. While widespread use of different spontaneously hypertensive strains may currently be complicating our understanding of the intermediate steps, studies of dissimilar strains should, in time, enhance our understanding of the many different facets of long-term blood pressure control.

Animals↗
PubMed1975

Angiotensin and the hemodynamics of chronic salt deprivation.

Salt deprivation has been shown to cause fluid volume contraction and marked renin release; it is not clear whether angiotensin-induced vasoconstriction adds to low volume in compromising circulatory function or whether there are additional facets to the salt-deprived state. Mature Wistar rats were fed a low-salt diet for 1 mo and then, under pentobarbital anesthesia, compared to normals. Arterial pressure (is congruent to 125 mmHg), cardiac output (is congruent to 200 ml/min per kg), and total peripheral resistance were nearly identical in both groups. The influence of angiotensin was estimated by injecting converting enzyme inhibitor (SQ 20881, 1 mg/kg), and then observing the immediate hemodynamic response. Salt-deprived rats responded with a large (-47 mmHg) fall in pressure and total peripheral resistance indicating that, although total peripheral resistance was normal in salt deprivation, an increased fraction (30% vs. 11%) of the resistance was supported by angiotensin. Cardiac output decreased (-8%) in contrast to the increase that would be expected during marked arterial dilation; elevated angiotensin levels may have caused a moderate, beneficial decrease in venous compliance. These results suggest that circulatory function is adequately maintained during salt deprivation by a combination of normal total peripheral resistance and decreased venous compliance.

Angiotensin II↗
PubMed1975

Separate roles of sodium ion concentration and fluid volumes in salt-loading hypertension in sheep.

The goal of these studies was to determine whether the hypertension caused by excessive salt loading results from sodium-induced expansion of the extracellular fluid volume or whether the salt increases the pressure in some other way, such as by causing vascular constriction. In one group of sheep, a combination of total nephrectomy and hemodialysis was used to produce and maintain step increases in extracellular fluid volume for 1 wk without a significant change in sodium ion concentration. In a 2nd group, unilateral nephrectomy, dialysis, and DOCA administration were used to cause step increases in sodium ion concentration while the extracellular fluid volume was held as close to normal as possible. The results showed a 41% increase in arterial pressure in the high-volume sheep and only a 4% increase in pressure in the high-sodium sheep. In both instances the total exchangeable sodium increased almost equally--a 21% increase in the high-sodium sheep. The data support the concept that sodium retention causes hypertension almost entirely because of sodium-induced expansion of the extracellular fluid volume.

Animals↗