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Biomedical subjects

A C Guyton

Publications and source records attributed to A C Guyton.

At least 19 recordsLinked to original sources
PubMed1992

Hemodynamic changes in rats after opening an arteriovenous fistula.

Time course of multiple hemodynamic changes in rats after opening an AV fistula was assessed. The fistula was made in male Sprague-Dawley rats by anastomosing the aorta and vena cava below the renal arteries. At 1 h (1H), 1 day (1D), 1 wk (1W) and 5 wk (5W) in sham controls or after opening an AV fistula, we measured cardiac output (CO) and tissue flows by using radioactive microspheres. The flow of microspheres to the lungs was used as a measure of shunt flow. In the fistula animals this lung flow (fistula flow) was 50-77% of the CO compared with 1-3% in the control animals. Cardiac index in the fistula animals increased by 40, 107, 129, and 307% compared with the respective control animals in the consecutive time groups. Systemic flow, tissue flows, and mean arterial blood pressure (MAP) in the fistula animals in the 1H and 1W groups were significantly decreased below control values, but each of these variables returned to control levels after 5W. Hematocrit (Hct) significantly decreased, whereas right atrial pressure (RAP) gradually increased over the experimental period. These two observations suggest retention of fluid. Plasma renin activity increased in the 1H animals but returned to control in the 1D animals. Atrial natriuretic peptide (ANP) gradually increased throughout the 5 wk from 86 +/- 22 (1H) to 709 +/- 217 pg/ml (5W). The increase in ANP correlated with the increase in RAP. Calculated total peripheral resistance in fistula animals was significantly decreased throughout the experiments.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Hemodynamic studies in DOCA-salt hypertensive rats after opening of an arteriovenous fistula.

We determined the cardiovascular responses in normal and deoxycorticosterone acetate (DOCA)-salt hypertensive rats with reduced total peripheral resistance due to an arteriovenous (a-v) fistula. Animals were divided into four groups: control, fistula, DOCA-salt, and DOCA-salt fistula. The fistula was made by anastomosing the aorta and vena cava below the renal arteries. Four weeks after the creation of the fistula both DOCA-salt and DOCA-salt fistula animals received DOCA and salt for 6-8 wk. At the end of 10-12 wk we measured mean arterial pressure, cardiac output, tissue flows, and right atrial pressure. Flow measurements using radioactive microspheres were made in anesthetized animals. Cardiac index (CI) was 202% higher in the fistula group than in the control animals and 165% higher in the DOCA-salt fistula than in the DOCA-salt animals. There was no difference in cardiac output between the control and DOCA-salt animals. The increase in cardiac output was due to the fistula flow as evidenced by a significant increase in the number of microspheres in the lung. Mean arterial pressure was 115 +/- 4 mmHg (control) and 108 +/- 5 mmHg (fistula) in non-DOCA rats but increased in both DOCA groups, 159 +/- 3 mmHg (DOCA-salt) and 145 +/- 5 mmHg (DOCA-salt fistula). Right atrial pressure was increased above control in both fistula animals but was normal in DOCA-salt animals. Total peripheral resistance (TPR) was higher than control in DOCA-salt animals, but TPR in both the fistula and DOCA-salt fistula animals was lower than control.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Kidneys and fluids in pressure regulation. Small volume but large pressure changes.

The human body has multiple blood pressure control mechanisms, each of which serves a special and usually different role in pressure regulation. The nervous pressure controllers usually react within seconds and prevent major rapid changes in pressure when acute extraneous forces act on the circulatory system. Then, within minutes to hours, several intermediately acting pressure controllers become activated. Among the more important of these are the renin-angiotensin-vasoconstriction system and the shift of fluid volume between the blood and interstitial fluids. Finally, after several hours to days, the kidneys readjust body fluid volumes, especially the extracellular fluid and blood volumes, to bring the pressure to a very precise level. This final adjustment usually requires little change in body fluid volume for two reasons. First, the other pressure controllers often have already made most of the needed pressure adjustments. Second, the increase in fluid volume required to cause a major increase in blood pressure is usually surprisingly small; this is true because the whole body blood flow autoregulation mechanism causes a secondary increase in total peripheral resistance.

Animals↗
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↗
PubMed1991

Blood pressure control--special role of the kidneys and body fluids.

The arterial pressure of the adult human rarely deviates from normal by more than 10 to 15 percent during each day. To achieve such constancy, the body has a network of pressure control systems. Several are based on neural receptors that respond within seconds to help correct any abnormal pressure. The activities of these systems are followed within minutes by activation of hormonal controllers. Within hours or days, a kidney pressure control system is induced that increases body fluid volume when the pressure falls (or decreases the volume when the pressure rises). This kidney-fluid system is the dominant method of establishing long-term pressure control.

Adult↗
PubMed1991

Effect of skin concavity on subcutaneous tissue fluid pressure.

We tested the hypothesis that mechanical factors associated, with a skin concavity can cause the local tissue fluid pressure to become more negative. Perforated Teflon collars, 26 mm in diameter and having various heights (5, 10, 13, and 16 mm), were implanted into the fascial plane of the inguinal and abdominal areas of six sheep. After several weeks, visible signs of edema were no longer apparent, and the skin formed a concavity within the center of each collar. The depth of each concavity was measured using an electronic micrometer, and the tissue fluid pressure beneath the concavity was measured using a needle method. Over the entire range of collar heights, the average depth of the concavities ranged from 1.1 to 4.7 mm in the abdominal tissues and from 1.8 to 5.5 mm in the inguinal tissues. The respective values of tissue fluid pressure averaged -4.6 to -13.0 and -5.7 to -12.8 mmHg. The results therefore indicate that implanting deeper collars leads to the formation of deeper concavities in the skin and also to greater negativity in the free tissue fluid pressure beneath the skin. Linear regression extrapolation to a collar height of 0 mm corresponded to a tissue fluid pressure of -1.0 mmHg in the abdominal tissue and -2.4 mmHg in the inguinal tissues. A model based on excessive pumping of the lymphatic system in the vicinity of a concavity is provided to explain this newly described phenomenon. We conclude that mechanical factors associated with the formation of a skin concavity cause or permit the tissue fluid pressure to reach levels of negativity far greater than those that exist in the absence of a concavity.

Abdomen↗
PubMed1991

Time course of renal responses to greater splanchnic nerve stimulation.

The objective of the present study was to describe the time courses of renal responses during renal sympathetic stimulation and to determine whether the kidney can provide a sustained response to sympathetic stimulation for 3 h. In four pentobarbital sodium-anesthetized dogs, stimulation (3.3 Hz) of a greater splanchnic nerve (GSN) on one side caused reductions in renal blood flow (RBF) and sodium excretion (UNaV) of both stimulated and contralateral-denervated kidneys, plus an increase in plasma renin activity (PRA). During continued stimulation, RBF partially recovered, but UNaV fell to less than 5% of control and PRA rose and remained at least eight times above control. In nine dogs, a single GSN was stimulated after ipsilateral adrenal medullectomy and ligation of the splanchnic circulation. The acute response to GSN stimulation was now confined to the ipsilateral kidney. Ipsilateral RBF fell by 32 +/- 10% but returned to 85 +/- 5% of control values by the end of the stimulation period. Contralateral RBF fell slowly by approximately 10%. Ipsilateral and contralateral UNaV fell to 34 +/- 10 and 43 +/- 11% of control values, respectively. PRA increased rapidly at the onset of GSN stimulation and remained at least 2.8 times control levels. After stimulation, RBF, UNaV, and PRA returned toward control levels. These results confirm the findings of others that the response of the renal vasculature to sympathetic stimulation is mainly transient. However, they additionally demonstrate a strong and sustained decrease in UNaV lasting for the total 3-h period of sympathetic stimulation.

Adrenal Medulla↗
PubMed1991

Abnormal renal function and autoregulation in essential hypertension.

The goal of this presentation has been to emphasize two fundamental mechanisms in the development of essential hypertension. These are: 1) The basic cause of essential hypertension is the inability of the kidneys to excrete an adequate volume of urine at normal arterial pressure. Therefore, fluid accumulates in the body until the pressure rises high enough to balance fluid output with fluid intake. This fluid balancing act is an infinite gain feedback system for controlling arterial pressure to a very precise level determined by the kidneys. Furthermore, this infinite gain allows the kidney mechanism to dominate the other pressure control mechanisms for long-term pressure control. Because of this domination, as long as a person has normal intake of water and electrolytes, essential hypertension cannot develop without an elevated pressure setting of the kidneys. 2) An increase in total peripheral resistance will not cause hypertension as long as the kidneys can still excrete normal amounts of water and electrolytes at normal arterial pressure, because loss of excess fluid volume at high pressures will simply reduce the cardiac output until the pressure falls back to normal. Therefore, what is the cause of the very high total peripheral resistance found in almost all patients with essential hypertension? The answer is likely the long-term blood flow autoregulation mechanism that occurs in virtually all tissues of the body. That is, when the pressure rises too high for whatever reason, this in turn forces too much blood flow through the tissues. In response, the local blood flow control mechanisms all over the body increase the vascular resistances until the flows return to normal.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Pressure↗
PubMed1990

Long-term arterial pressure control: an analysis from animal experiments and computer and graphic models.

Long-term arterial pressure control is very different from acute control, because many of the acute control systems are overridden by a single long-term mechanism that has little to do with short-term control. This is the renal fluid volume mechanism for pressure control. It is based on a simple functional property of the kidney: as the arterial pressure rises, the kidney output of water and electrolytes increases dramatically. When the output rises above the net intake of water and electrolytes, negative body fluid balance occurs, causing both the body fluid volume and the pressure to decrease. This decrease continues until the kidney fluid output exactly balances the net fluid intake. Conversely, if the pressure falls below the exact level for balance, intake becomes greater than output; then fluid builds up in the body and the pressure rises until intake and output again exactly balance each other. This fluid mechanism for pressure control has been known from the beginning of blood pressure research. However, its overpowering importance was not appreciated until a mathematical computer analysis in 1966 demonstrated the renal-fluid feedback mechanism to have infinite feedback gain for long-term pressure control. This is the principal topic of the present review.

Animals↗
PubMed1990

The surprising kidney-fluid mechanism for pressure control--its infinite gain!

In this short paper, I have tried to explain the elation that we felt when we first realized that the kidney-fluid mechanism for controlling the arterial pressure has an infinite feedback gain property. Because of this, all the other pressure control mechanisms, none of which has ever been shown to have a similar infinite gain property, must themselves alter the kidney-fluid mechanism if they are to succeed in causing long-term changes in the arterial pressure. We have not been able to refute this principle despite many experiments over the last 2 decades. For this reason, our first understanding of the infinite gain property of the kidney-fluid mechanism was like a light at the end of the tunnel. I hope that I can explain to the reader the excitement of those few seconds when we first recognized the principle in 1966.

Animals↗
PubMed1990

Renal function curves and control of body fluids and arterial pressure.

The purpose of this paper has been to emphasize the extreme importance of the renal function curve in determining the long-term level of arterial pressure. The reason for this importance is that the renal-body fluid-pressure control system exhibits the phenomenon of "infinite feedback gain". This is, the arterial pressure will stabilize only when the intake and output of water and salt becomes exactly equal, and this occurs at only one very exact pressure level for any given renal function curve and given salt intake level. This renal mechanism for controlling the body fluids and simultaneously controlling the arterial pressure, because of its infinite feedback gain capability for controlling arterial pressure, requires that other pressure control mechanisms must interact with this mechanism either to alter the renal function curve or to make the animal change its intake of salt and water if the other pressure mechanisms are to have any effect on the long-term arterial pressure level. Therefore, in virtually any analysis of long-term arterial pressure regulation, the renal function curve or its mathematical equivalent plays a central role.

Animals↗
PubMed1990

Role of the renin-angiotensin system in control of sodium excretion and arterial pressure.

The RAS is part of an extremely powerful feedback system for long-term control of arterial pressure and volume homeostasis as illustrated in Figure 4. Disturbances that tend to lower blood pressure such as heart failure, cirrhosis, and peripheral vasodilation, cause sodium and water retention until blood pressure returns to normal due in large part to the combined actions of ANGII and reduced renal perfusion pressure. In response to disturbances such as high sodium intake, suppression of ANGII greatly amplifies the effectiveness of the basic pressure natriuresis and diuresis mechanism, thereby preventing large increases in body fluid volumes and blood pressure. In circumstances in which the RAS is inappropriately activated, the sodium-water retaining effects of ANGII necessitate increased blood pressure to maintain sodium and water balance via pressure natriuresis. The sodium retaining actions of the RAS are mediated by intrarenal as well as extrarenal mechanisms. The intrarenal actions of ANGII include a direct effect on tubular sodium transport as well as a potent constrictor action on efferent arterioles which increases tubular reabsorption by altering peritubular capillary physical forces. The constrictor action of ANGII on efferent arterioles also plays an important role in stabilizing GFR and therefore in preventing fluctuations in excretion of metabolic waste products that depend upon a high GFR for excretion. ANGII is known to stimulate proximal reabsorption, but the effects on more distal tubular segments have not been completely elucidated. The primary extra-known to stimulate proximal reabsorption, but the effects on more distal tubular segments have not been completely elucidated. The primary extra-renal effect of ANGII which influences sodium excretion is stimulation of aldosterone secretion. Current evidence, however, suggests that the various intrarenal actions of ANGII are quantitatively more important in causing sodium retention than those mediated by changes in aldosterone secretion. However, the combined intrarenal and extrarenal actions of ANGII on sodium reabsorption provide the body with one of its most potent feedback systems for long-term regulation of body fluid volumes and arterial pressure.

Animals↗
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

Dominant role of the kidneys and accessory role of whole-body autoregulation in the pathogenesis of hypertension.

In this paper I have presented two closely related themes both of which seem to be fundamental in understanding the pathophysiology of hypertension. The first theme is the dominant role of the volume-excretion function of the kidneys in setting the long-term arterial pressure level. That is, each person in general has a rather steady intake of salt, water, and those other constituents that make up extracellular fluid. When the arterial pressure is normal, the kidney excretion of these constituents is exactly the correct amount to balance the intake of each of them. When the pressure is too great, there is more loss than gain, and the body fluid volume decreases; therefore, the pressure falls until the exact balance point is reached again; it is only at this balance point that the loss and gain are equal. At any pressure below the balance point, volume gain is greater than loss, and the pressure will continue to rise until the exact balance level is again reached. This capability of the kidney mechanism to return the pressure all-the-way back to the level of balance between input and output--not merely part-way back--is called the "infinite gain" characteristic of this pressure control system, and the level to which the pressure is controlled is called the "set-point" of the system. In pathophysiological states, the set-point for pressure control can be increased to hypertensive levels as a result of (1) a pathophysiological change in renal function or (2) increased salt and volume intake; then hypertension will ensue. Other abnormalities of circulatory function that do not affect one of these two factors cannot cause chronic hypertension because of the infinite gain feature of the renal-volume mechanism for pressure control. One such condition that does not cause hypertension without some concurrent abnormality that affects renal function is a primary increase in total peripheral resistance. The second theme is that whole-body autoregulation causes the blood flow in all parts of the body to return or remain near to normal when high arterial pressure tries to increase the flow. It does this by increasing the resistance in all parts of the peripheral arterial tree. Therefore, in effect, autoregulation converts any tendency to high cardiac output hypertension into high resistance hypertension. Yet, in so far as is now known, the pressure level will be the same with or without autoregulation.(ABSTRACT TRUNCATED AT 400 WORDS)

Chronic Disease↗
PubMed1989

Regulation of cardiac output during aldosterone-induced hypertension.

The classical haemodynamic transients of volume-loading hypertension have been difficult to demonstrate in aldosterone-induced hypertension. Because recent studies have shown that continuous whole-day measurements of cardiac output are superior to short-term recordings, we studied the transient haemodynamic effects of aldosterone-induced hypertension while monitoring arterial pressure and cardiac output (electromagnetic flow probe) continuously for 20 h a day. In six dogs maintained on a fixed sodium intake of 150 mmol/day, we infused aldosterone (12 micrograms/kg per day, intravenously) for 10 days. The aldosterone induced a progressive increase in mean arterial pressure, from a control value of 88 +/- 1 to 107 +/- 2 mmHg. Cardiac output increased progressively, reaching a peak average value on the 4th day of infusion of +14 +/- 5% above control, and remained slightly elevated throughout the infusion period. Total peripheral resistance increased slowly to a value averaging +13 +/- 4% above control. Therefore, our experiments show that aldosterone induces a primary increase in cardiac output followed by a secondary vasoconstriction, which is consistent with the classical transient haemodynamic effects of volume-loading hypertension.

Aldosterone↗
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↗
PubMed1989

Vascular development in chick embryos: a possible role for adenosine.

We studied the possible role of adenosine in the development of the vasculature using 217 chick embryos. Adenosine (2-32 mumol/day), inosine (16 mumol/day), dipyridamole (0.04-0.4 mumol/day), or aminophylline (400 and 800 micrograms/day) were administered twice each day into the air space on days 11-14. Control embryos received Ringer solution. Whole body vascularity was estimated on day 15 as the whole body structural vascular resistance (SVR), i.e., the hydraulic resistance of the maximally dilated vasculature. Adenosine decreased the SVR in a dose-related manner at the lower dosage amounts but caused a maximum decrease in SVR at the higher dosage amounts averaging 30% below the Ringer control values. Equimolar amounts of adenosine and inosine decreased the SVR by the same extent. Dipyridamole, which potentiates the biological effects of endogenous adenosine, also decreased the SVR in a dose-related manner to values averaging approximately 30% below control. When the effects of endogenous adenosine were blocked by aminophylline, the SVR increased in a dose-related manner to approximately 100% above control at the highest dosage amount. These results suggest that adenosine could have a physiological role in growth regulation of the vascular system in the chick embryo.

Adenosine↗