Biomedical subjects

S L Britton

Publications and source records attributed to S L Britton.

At least 37 records · Page 2Linked to original sources

PubMed1993

Spontaneous pressure-flow relationships in renal circulation of conscious dogs.

Renal pressure-flow (P-F) relationships are usually evaluated by measuring effects of mechanically induced changes in renal arterial pressure (AP) on renal blood flow (RBF). We devised a method allowing evaluation of renal P-F relationships during normal changes in AP occurring spontaneously in a conscious animal rather than during artificially induced changes in AP. In 18 trials in 6 dogs standing at rest, we measured average AP and RBF for each cardiac cycle over periods of approximately 35 min (approximately 3,100 cardiac cycles/trial). AP and RBF values for each cardiac cycle were expressed as percent change (%delta) from the 35-min average (beat-to-beat changes). Slope and angle of each consecutive beat-to-beat P-F change were calculated and collated into one of eight zones representing the possible physiological mechanisms responsible for concurrent, spontaneous changes in RBF and AP. In a predominance of the cardiac cycles (approximately 43%), the spontaneous AP-RBF relationship was consistent with being mediated by arterial baroreflexes (i.e., increases in AP were accompanied by proportionately greater increases in RBF during 44.4% of cardiac cycles in which AP increased, and decreases in AP were accompanied by proportionately greater decreases in RBF during 41.4% of cardiac cycles in which AP decreased). Blockade of autonomic ganglionic transmission with hexamethonium markedly attenuated this pattern. Our results indicate that renal circulation participates in moment-to-moment control of AP via a predominant baroreflex-like pattern.

Animals↗

PubMed1993

Spontaneous pressure-flow patterns in the kidney of conscious rats.

We have developed a model that permits a quantitative analysis of the contribution of different mechanisms to the spontaneously occurring pressure-flow patterns of a vasculature. In this study we evaluated the spontaneous relationship between arterial pressure (P) and renal blood flow (F) in resting conscious rats during control conditions, autonomic ganglionic blockade (hexamethonium), and nonselective alpha-adrenoreceptor blockade (phentolamine). In a total of 250 trials in 29 rats, we measured the average P and F for each cardiac cycle over 13-min periods (approximately 4,000 cardiac cycles/trial). The P and F values for each cardiac cycle were expressed as percentage change from each 13-min average (beat-to-beat changes). The slope and angle of each consecutive beat-to-beat P-F change were calculated and collated into one of eight zones representing the physiological mechanisms responsible for the concurrent spontaneous changes in P and F. Our results reveal that, in the absence of any chemical or mechanical intervention (control), the renal circulation demonstrated a baroreflex-like P-F pattern approximately 38% of the time. An autoregulatory-like P-F pattern occurred, at the most, 35% of the time. Autonomic ganglionic blockade significantly (P < 0.05) decreased the baroreflex-like pattern and increased the presence of P-F patterns indicative of autoregulation. alpha-Adrenoreceptor blockade resulted in a P-F pattern that was qualitatively similar to that produced by hexamethonium, but with considerably more variability. These results indicate that, in the resting conscious undisturbed state, the autonomic nervous system exerts a tonic influence on the renal circulation that facilitates arterial pressure regulation via a baroreflex-like pattern.

Adrenergic alpha-Antagonists↗

PubMed1993

Dynamic, short-term coupling between changes in arterial pressure and urine flow.

Pressure diuresis refers to the direct effect of arterial pressure (AP) on the rate of urine flow (UF). On the basis of computer modeling, pressure diuresis has been viewed as a long-term mechanism that acts to set the level of the blood volume and, thus, the steady-state AP. There are no systematic studies, however, on the rapidity with which changes in AP induce changes in UF in vivo. Therefore, we measured the delay between induced changes in AP and the subsequent change in UF. Nine anesthetized rats were instrumented with arterial, venous, and ureteral catheters. AP and UF were measured every 2 s, while acute changes in AP were induced by 1) occlusion of the aorta above or below the renal vessels; 2) brief tail pinch; or 3) intravenous administration of acetylcholine (1 microgram), phenylephrine (1 microgram), or angiotensin II (0.1 microgram). The rapidity of the urinary response to induced changes in AP was determined by calculating the delay between a significant change in AP (+/- 2 SD from baseline) and a significant change in UF. The delay averaged 6.0 +/- 0.5 s for all conditions. Also, examining the relationship between the magnitude of the induced changes in AP and the magnitude of the responses in UF revealed an exponential influence of AP on UF. That is, there were proportionately larger changes in UF compared with AP (< or = 10 times greater magnitude) in response to the experimental interventions.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗

PubMed1993

Gravimetric method for the dynamic measurement of urine flow.

The rate of urine formation is a primary index of renal function, but no techniques are currently available to accurately measure low rates of urine flow on a continuous basis, such as are normally found in rats. We developed a gravimetric method for the dynamic measurement of urine flow in anesthetized rats. Catheters were inserted directly into the ureters close to the renal pelves, and a siphon was created to collect all of the urine formed as rapidly as it was produced. Urine flow was determined by measuring the weight of the urine using a direct-reading analytical balance interfaced to a computer. Basal urine flow was measured at 2-sec intervals for 30 to 60 min. The dynamic response of urine flow to a rapid decrease in arterial pressure produced by a bolus intravenous injection of acetylcholine (0.5 micrograms) was also measured. Intrinsic drift, evaporative losses, and the responsiveness of the system to several fixed pump flows in the low physiologic range were evaluated in vitro. The gravimetric method described was able to continuously measure basal urine flows that averaged 37.3 +/- 12.4 microliters/min. Error due to drift and evaporation was negligible, totaling less than 1% of the measured urine flow. Acetylcholine-induced declines in arterial pressure were followed within 8 sec by a decline in urine flow. These data demonstrate that this new gravimetric method provides a simple, inexpensive, dynamic measurement of urine flow in the microliter/min range.

Acetylcholine↗

PubMed1991

Reflex versus autoregulatory control of hindlimb blood flow during treadmill exercise in dogs.

To evaluate the competition between local autoregulation and reflex neurohumoral control of hindlimb blood flow (HLBF), the hindlimb vascular pressure-flow relationship was determined in nine dogs in response to a 10% decrease in mean arterial pressure (AP) imposed during both low (3.0 km/h, 0% grade) and high (5.5 km/h, 14% grade) intensities of treadmill exercise. HLBF was measured with a Doppler flow probe on the left external iliac artery, and AP was controlled with a gravity reservoir connected to the left carotid artery. A 10 +/- 2% reduction in AP for 25 min caused HLBF to decrease 25 +/- 2% during low-exercise intensity but only 10 +/- 2% during high-exercise intensity. The corresponding closed-loop gains (Gc) of HLBF regulation [Gc = 1 - (% delta hindlimb blood flow/% delta hindlimb perfusion pressure) were -1.6 +/- 0.4 and -0.06 +/- 0.2 during low- and high-exercise intensity, respectively. Autonomic ganglionic blockade (hexamethonium) increased the Gc during low-intensity exercise to 0.07 +/- 0.2. Antagonism of adenosine receptors (aminophylline) decreased the Gc of HLBF regulation during high-intensity exercise to -0.57 +/- 0.3. These data demonstrate that in response to an imposed decrease in AP, autonomic vasoconstriction overrides autoregulatory vasodilatory mechanisms during low-intensity exercise. HLBF regulation increases at a higher exercise intensity, in part due to adenosine, but autoregulation does not predominate over arterial pressure regulating mechanisms.

Adenosine↗

PubMed1991

Autoregulatory capacity in renal and mesenteric vasculatures of mineralocorticoid hypertensive dogs.

Experiments were performed in seven conscious dogs to quantitate the renal and mesenteric autoregulatory capacity in deoxycorticosterone acetate (DOCA)-salt hypertensive dogs. Each dog was chronically instrumented for the measurement of aortic blood pressure and blood flows through the superior mesenteric and left renal arteries (Doppler measurements); a right nephrectomy was also performed. To induce hypertension, animals were administered 5 mg/kg DOCA each day and given 1% saline as a drinking solution. After arterial pressure had increased by 25% (8-14 days of DOCA), a large-bore catheter was positioned retrograde in the left common carotid artery for subsequent connection to a gravity reservoir system for acute control of arterial pressure. Autoregulatory capacity was evaluated by controlling arterial pressure via the gravity reservoir at hypertensive and then normotensive values for 15-min periods. In neurally intact animals the renal, but not the mesenteric, circulation displayed autoregulatory capacity; the closed-loop gain of renal flow control averaged 0.92 +/- 0.06. Inhibition of autonomic ganglionic transmission (hexamethonium) increased the gain of flow regulation in the mesenteric circulation, but mesenteric autoregulation was not manifest. Ganglionic blockade, inhibition of prostaglandin formation, or blockade of histamine or adenosine receptors did not significantly influence renal autoregulatory capacity. These data demonstrate that the kidney has a high capacity to autoregulate in DOCA hypertension and suggest that autoregulatory-mediated renal vasoconstriction contributes to the increased total peripheral resistance.

Adenosine↗

PubMed1991

Pressure diuresis and autonomic function in conscious dogs.

Pressure diuresis is thought to be a major long-term regulator of arterial blood pressure (AP). Previously, pressure diuresis has been characterized using pharmacological or surgical blockade of other mechanisms known to affect renal function. This study evaluated pressure diuresis in conscious dogs with minimal experimental interference. Dogs were chronically instrumented under pentobarbital anesthesia with aortic and urinary bladder catheters. AP was increased by 10% in resting dogs by exposure to increased light and sound intensity (arousal) for 90 min. During arousal, urine flow (UV) and Na+ excretion (UNa+ V) correlated with AP (UV vs. AP, r = 0.12, P less than 0.05; UNa+ V vs. AP, r = 0.19, P less than 0.005; 17 trials in 7 dogs). Arousal did not affect the plasma concentration of atrial natriuretic factor, suggesting that this hormone did not contribute to the correlations between UV or UNa+ V and AP. Because arousal may induce an autonomically mediated antidiuresis, studies were repeated during autonomic ganglionic blockade with hexamethonium. During autonomic blockade, the correlations between UV or UNa+ V and AP were increased (UV vs. AP, r = 0.72; UNa+ V vs. AP, r = 0.72, P less than 0.001; 6 trials in 4 dogs). We conclude that the effect of pressure diuresis on UV and UNa+ V can be detected in the intact animal, during normal operation of all the mechanisms that control renal function. Furthermore, when autonomic reflexes are blocked, the pressure-diuresis mechanism is a major determinant of UV and UNa+ V.

Animals↗

PubMed1990

Adenosine is not essential for exercise hyperaemia in the hindlimb in conscious dogs.

1. The contribution of endogenous adenosine to the increase in hindlimb blood flow that occurs during treadmill exercise was evaluated in conscious dogs. We postulated that if adenosine is essential for the hindlimb hyperaemic response, then pharmacological treatment of the animals with adenosine receptor antagonists should decrease hindlimb blood flow during treadmill exercise. 2. A total of twenty-three dogs were chronically instrumented for measurement of aortic blood pressure and hindlimb blood flow using electromagnetic or Doppler flow probes on the left external iliac artery. Measurements of arterial blood pressure, hindlimb blood flow and heart rate were made during steady-state treadmill exercise in both the presence and the absence of adenosine receptor antagonists. Four different protocols were performed using different routes of administration of two adenosine receptor antagonists. Aminophylline was used in most of the experiments, and the effects of the more potent antagonist, 8-phenyltheophylline, were also evaluated. In addition, the dogs exercised at varying intensities ranging from a low level of 5.5 km h-1 at 0% gradient to a high intensity of 5.5 km h-1 at 21% gradient. 3. Aminophylline given as a single intravenous dose, or as a constant infusion either intravenously or directly into the hindlimb artery, did not decrease hindlimb blood flow at low, moderate or high intensities of exercise. Likewise, the blockade of adenosine receptors with 8-phenyltheophylline, given systemically or as a bolus injection administered directly into the hindlimb circulation during moderate exercise, did not attenuate the hindlimb blood flow response. 4. Our data demonstrate that exercise hyperaemia of the hindlimb is not reduced by antagonism of adenosine receptors. These findings are consistent with the hypothesis that adenosine is not an essential mediator of hindlimb vasodilatation during exercise.

Adenosine↗

PubMed1989

Systemic vascular autoregulation amplifies pressor responses to vasoconstrictor agents.

Experiments were performed in seven conscious dogs to evaluate the contribution of total systemic autoregulation to the increase in mean arterial pressure (MAP) produced by the intravenous administration of pressor agents. Each dog was instrumented for the measurement of aortic pressure, central venous pressure, and cardiac output, and all dogs received hexamethonium to block autonomic ganglionic transmission. Angiotensin II (ANG II), arginine vasopressin (AVP), or norepinephrine (NE) were titrated over a 15- to 20-min period until MAP was increased to a new steady-state value approximately 50-55% above the normotensive control. Then while a constant infusion of the pressor agents was maintained, MAP was controlled via a gravity reservoir for 15-min periods at either the hypertensive value or at the animal's normotensive value. With all three pressor agents, total peripheral resistance (TPR) was greater when MAP was controlled at the hypertensive value than when the vasculature was protected from the elevated pressure by controlling MAP at the normotensive value. Thus a portion of the increase in TPR during the infusion of ANG II, AVP, or NE was due to autoregulatory-mediated vasoconstriction elicited by the increase in MAP. The fractions of the increases in TPR and MAP contributed by primary vasoconstriction vs. autoregulation were determined from the pressure-flow relationships. The pressure-induced increases in TPR accounted for 74% of the total increase in MAP produced by AVP, 62% of the pressor response to NE, and 34% of the response to ANG II. These results demonstrate that the direct vasoconstrictor effects of pressor agents can be significantly amplified by secondary autoregulatory responses.

Algorithms↗

PubMed1989

Quantitative contribution of systemic vascular autoregulation in acute hypertension in conscious dogs.

Experiments were performed in nine conscious dogs to quantitate the contribution of systemic vascular autoregulation to the increases in total peripheral resistance (TPR) and mean arterial pressure (MAP) produced by angiotensin II (ANG II), arginine vasopressin (AVP), and norepinephrine (NE). We hypothesized that if autoregulatory vasoconstriction is significant, then the increase in TPR produced by vasoconstrictor infusion will be greater when MAP is controlled at hypertensive values than when the increase in pressure is prevented by controlling MAP at the animal's normotensive value. Each drug was infused at a dose sufficient to increase MAP by 50%. Then, a constant rate of vasoconstrictor infusion was maintained while MAP was controlled at hypertensive or normotensive levels for 15-min periods using a gravity reservoir connected to the left common carotid artery. During AVP infusion, TPR was significantly greater when MAP was controlled at hypertensive than at normotensive values. This autoregulatory-mediated vasoconstriction accounted for approximately three-fourths of the increase in MAP produced by AVP. No significant autoregulatory component was identified for the increases in TPR and MAP produced by ANG II or NE. We conclude that systemic vascular autoregulation is a powerful physiological property that contributes to the hemodynamic response to pressor doses of AVP.

Angiotensin II↗

PubMed1988

Evaluation of whole body autoregulation in conscious dogs.

The ability of the systemic circulation to maintain cardiac output during decreases in arterial pressure was evaluated in conscious dogs with intact reflexes (n = 8) and during pharmacological blockade of the autonomic nervous system, angiotensin II formation, and arginine vasopressin (n = 6). Cardiac output was measured electromagnetically, and aortic pressure was controlled via a gravity reservoir connected to a carotid artery. When aortic pressure was decreased in either small steps to approximately 60% of control, or decreased in a single square-wave step to 75% of control and maintained for 2 h, cardiac output decreased to the same or a greater extent in both control and areflexic dogs. Thus total peripheral resistance did not decrease, and autoregulation of the cardiac output did not occur in response to short-term (less than or equal to 2 h) decreases in arterial pressure, even in the absence of the major pressor systems. After long-term (greater than 8 h) decreases in arterial pressure to 75% of control in five dogs with all reflexes intact, significant autoregulation of the cardiac output occurred. The relationship between the gain of blood flow autoregulation and the corresponding values of mixed venous oxygen tension suggests that whole body autoregulation results when oxygen extraction reserve becomes limited.

Angiotensin II↗

PubMed1988

Support of arterial blood pressure by major pressor systems in conscious dogs.

The roles of the autonomic nervous system, vasopressin, and angiotensin II in support of blood pressure were evaluated in seven conscious, resting dogs while hydrated or dehydrated. Mean arterial blood pressure (MAP) was monitored, and the dogs were given hexamethonium to block autonomic ganglia. Thirty minutes later, they were given captopril, and after another 30 min, a vasopressin V1 antagonist, d(CH2)5TyrMeAVP, was given. The order okf administration of captopril and d(CH2)5TyrMeAVP was alternated in different experiments. Hexamethonium had no effect on steady-state MAP in either hydrated or dehydrated dogs. In hydrated dogs, the average MAP was 100 mmHg; d(CH2)5TyrMeAVP decreased MAP by approximately 12 mmHg, and captopril decreased MAP by 24 mmHg. The magnitude of the effect of these two inhibitors was independent of the order of their administration. Dehydration doubled the effect of d(CH2)5TyrMeAVP on MAP but had no effect on the response to captopril. The results suggest that 1) autonomic function is not essential for maintenance of arterial blood pressure in resting dogs; 2) during autonomic ganglionic blockade, arterial blood pressure is supported by both angiotensin II and vasopressin; and 3) dehydration increases the role of vasopressin in control of blood pressure.

Angiotensin II↗

PubMed1987

Enzymatic formation of angiotensins II and III in the hindlimb circulation of dogs.

Experiments were performed in 14 anesthetized dogs to (1) to determine if the reductions in hindlimb blood flow produced by [des-Asp1] angiotensin I were due to its local enzymatic (kininase II) conversion to angiotensin III and (2) to quantitate the extent of conversion of angiotensin I to angiotensin II and of [des-Asp1] angiotensin I to angiotensin III in the hindlimb circulation. Graded doses of these peptides were administered as bolus injections directly into the left external iliac artery while measuring flow in this artery electromagnetically. Dose-response relationships were determined before and during the inhibition of kininase II activity with captopril or antagonism of angiotensin receptor sites with [Ile7] angiotensin III. Captopril inhibited the vasoconstrictor responses to angiotensin I and [des-Asp1] angiotensin I, but did not affect the responses to angiotensins II or III, or norepinephrine. [Ile7] angiotensin III inhibited the vasoconstrictor responses to all four angiotensin peptides but did not alter the responses to norepinephrine. These findings indicate that the hindlimb vasoconstrictor responses to [des-Asp1] angiotensin I were due to the local formation of angiotensin III. The extent of conversion of [des-Asp1] angiotensin I to angiotensin III that occurred in one transit through the hindlimb arterial circulation was estimated to be 36.7%, which was not different from the estimated 36.4% conversion of angiotensin I to angiotensin II. We conclude that angiotensin I and [des-Asp1] angiotensin I are converted to their respective vasoactive forms (angiotensins II and III) to a similar extent in the hindlimb circulation via the action of kininase II.

Angiotensin I↗

PubMed1987

Constant-flow perfusion of the hindlimb vascular bed in conscious dogs.

Hindlimb vascular bed pressure-flow relationships were evaluated in seven conscious dogs using a newly developed controlled-flow perfusion technique. For controlled-flow perfusion, blood was diverted from a common carotid artery to a roller pump for perfusion of the left hindlimb vascular bed via an artificial vascular graft anastomosed to the left external iliac artery. An occlusion cuff positioned around the external iliac artery proximal to the graft arrested normal hindlimb blood flow during perfusion. Collateral flow was minimized by ligating all other major arteries supplying the left hindlimb. Hindlimb perfusion pressure, measured via the left deep femoral artery, decreased to a plateau value of 19.7 +/- 3.4 mmHg when pump flow was zero. Pressure-flow relationships were evaluated while the dogs were at rest by changing flow in small "square-wave" steps for 3 min each and measuring the steady-state perfusion pressure at each step. The hindlimb was perfused over a wide range of flows (25-450 ml/min) that resulted in perfusion pressures ranging from 40 to 175 mmHg. The hindlimb pressure-flow relationship obtained was indicative of net passive vascular behavior. That is, resistance to flow decreased with increases in flow, such that a curvilinear pressure-flow relationship occurred that was convex to the pressure axis. We conclude that the hindlimb circulation of resting conscious dogs can be perfused using controlled-flow perfusion techniques. These techniques can also be applied to other vascular beds and should be useful for evaluating peripheral vascular responses to drugs and reflexogenic alterations.

Animals↗

PubMed1986

Effect of aminophylline on hindlimb blood flow autoregulation during increased metabolism in dogs.

The contribution of adenosine to hindlimb blood flow autoregulation during treadmill exercise or the administration of 2,4-dinitrophenol (DNP) was evaluated in 9 conscious dogs by determining hindlimb vascular bed pressure-flow relationships in the presence and absence of the adenosine receptor site antagonist, aminophylline. Hindlimb pressure-flow relationships were obtained by measuring blood flow during stepwise reductions in perfusion pressure produced with an occlusion cuff located distal to a flow probe on the external iliac artery. The efficiency of autoregulation was quantitated by calculating the closed-loop gain of flow regulation (Gc) at each pressure decrement utilizing the equation Gc = 1 - (% delta flow/% delta pressure). A Gc of one represents perfect autoregulation of flow, and a Gc of zero is indicative of a rigid system. During exercise, Gc averaged 0.44 +/- 0.07. Aminophylline reduced the Gc during exercise to -0.07 +/- 0.06 (P less than 0.05). During DNP administration, Gc averaged 0.54 +/- 0.09 and declined to -0.09 +/- 0.10 in the presence of aminophylline (P less than 0.05). These results support the hypothesis that adenosine is a primary mediator of hindlimb blood flow autoregulation during conditions that increase hindlimb metabolism.

2,4-Dinitrophenol↗

PubMed1986

Evaluation of angiotensins II and III as vasoconstrictors in the hepatic and hindlimb vasculatures of dogs.

Previous work has demonstrated that intravenously administered angiotensin II is more potent than angiotensin III as a systemic vasopressor agent. We tested the hypothesis that this difference in potency is caused at least partially by angiotensin II being more potent than angiotensin III as a vasoconstrictor in the hindlimb and hepatic vasculatures. The effects of angiotensins II and III on hindlimb and hepatic blood flow were evaluated in 14 dogs anesthetized with pentobarbital. Blood flows were measured electromagnetically. Graded doses of angiotensins II and III were administered as bolus injections directly into the arterial supply of the hindlimb and liver. On the basis of duration and graphic integration of the flow responses, but not on the basis of absolute changes in amplitude, angiotensin II was significantly more potent than angiotensin III as a vasoconstrictor in the hindlimb vasculature. In the hepatic circulation the flow changes produced by angiotensin II and angiotensin III were not significantly different on the basis of duration, graphic integration, or amplitude. We conclude that (i) differential vasoconstrictor responses of the hindlimb, but not the hepatic circulation, to angiotensins II and III contribute to the difference in systemic vasopressor potency between these two peptides, and (ii) because flow responses are an integral event with duration and constantly varying amplitude, evaluation of vasoconstrictor potency based only upon amplitude of the flow changes can be misleading.

Angiotensin II↗

PubMed1985

Hematoporphyrin derivative photochemotherapy of experimental bladder tumors.

Recent studies have shown that disruption of tumor blood flow is a major consequence of hematoporphyrin derivative photochemotherapy. A series of experiments was undertaken on the transplantable N-(4-(5-nitro-2-furyl)-2-thiazolyl)-formamide induced urothelial tumor in Fischer 344 rats to determine a dose response for both hematoporphyrin derivative and light. Tumor blood flow was used as the biologic criteria of response. Hematoporphyrin derivative doses of 10 micrograms./gm. body weight or above were necessary to cause a significant decrease in tumor blood flow when the tumors were illuminated with 360 joules/cm.2 of noncoherent red light (greater than 590 nm.). With a constant hematoporphyrin derivative dose of 20 micrograms./gm. body weight, significantly lower tumor blood flows were observed with fluences of 240 joules/cm.2 and above. In order to correlate dose response to tumor regression, experiments were done in which tumor dry weights were determined 3 weeks after completion of photochemotherapy (360 joules/cm.2). Hematoporphyrin derivative doses of 10 micrograms./gm. body weight or above were necessary to induce tumor regression. These studies support the hypothesis that disruption of tumor blood flow is a tumoricidal mechanism of hematoporphyrin derivative photochemotherapy.

Animals↗

PubMed1985

Autoregulation of hind-limb blood flow in conscious dogs.

We evaluated the efficiency of blood flow autoregulation of the hind-limb vascular bed of eleven conscious dogs during: resting conditions; graded levels of treadmill exercise; and increases in oxygen consumption produced by the administration of 2,4-dinitrophenol (DNP). Blood flow to the left hind limb was measured with an electromagnetic flow probe on the left external iliac artery. Hind-limb perfusion pressure was measured from a catheter in the deep femoral artery and was controlled via an externally inflatable occlusion cuff positioned just distal to the flow probe. Arterial pressure was measured in the abdominal aorta. Experiments were performed 5-16 days after instrumentation. Hind-limb pressure-flow (P-F) relationships were evaluated by decreasing hind-limb perfusion pressure in 4-5 small sequential 'square-wave' steps of 10-15 mmHg each while measuring flow. Each step decrease in perfusion pressure was maintained for 2 min. The efficiency of autoregulation was quantified by calculating the closed-loop gain of flow regulation (Gc) at each decrement in perfusion pressure utilizing the equation: Gc = 1-[(F0-Fn/F0)/(P0-Pn/P0)] where F0 and P0 are the starting (control) flows and pressures prevailing prior to decreasing perfusion pressure, and Fn and Pn are the new flows and pressures at each decrement in perfusion pressure. A Gc value less than 0 indicates a predominantly passive P-F relationship, while a Gc of 1 is perfect autoregulation of flow. When the dogs were at rest, decrements in hind-limb perfusion pressure were accompanied by almost equivalent decreases in flow, i.e. no autoregulation occurred, and Gc averaged -0.177 +/- 0.044 over the pressure range from 100-40 mmHg. During all levels of treadmill exercise (on gradients of 0, 7, or 21%), however, positive Gc values were found that averaged from 0.258 +/- 0.046 at a gradient of 0% to 0.392 +/- 0.041 at a gradient of 21% and were significantly different from Gc values found during rest at perfusion pressure ranges from 90-40 mmHg. The administration of DNP directly into the hind-limb circulation increased hind-limb blood flow from 199 to 481 ml/min. In the presence of DNP, Gc values were positive over perfusion pressure ranges from 100-40 mmHg and averaged 0.473 +/- 0.054. These data demonstrate that hind-limb blood flow is not autoregulated in resting dogs, but that significant autoregulation is manifest during conditions that increase oxygen consumption.(ABSTRACT TRUNCATED AT 400 WORDS)

2,4-Dinitrophenol↗