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P H Brand

Publications and source records attributed to P H Brand.

18 recordsLinked to original sources
PubMed1994

Spontaneous changes in arterial blood pressure and renal interstitial hydrostatic pressure in conscious rats.

1. Previous work has demonstrated a positive relationship between experimentally induced changes in arterial pressure (AP) and renal interstitial hydrostatic pressure (RIHP). The purpose of the present study was to test the hypothesis that RIHP is positively correlated with the normal changes in AP that occur spontaneously in conscious rats. 2. Rats were chronically instrumented for the recording of AP (via an aortic catheter) and RIHP. RIHP was measured by implanting a Millar microtransducer, whose tip had been encapsulated in a 35 microns pore polyethylene matrix (5 mm long, 2 mm o.d.), approximately 5 mm below the renal cortical surface. 3. A total of 56 h of simultaneous analog recording of AP and RIHP was obtained from ten rats. Each 1 h segment was digitized and evaluated at frequencies of 1, 0.1, 0.02 and 0.01 Hz. 4. In forty-nine out of fifty-six of these 1 h recordings taken at 1 Hz, there were significant positive linear correlations between AP and RIHP (mean r = 0.32) with a mean slope of 0.11 mmHg RIHP/1 mmHg AP. Low-pass filtering to 0.01 Hz significantly increased the r value to 0.48. 5. These results demonstrate that spontaneous changes in AP and RIHP are positively correlated. The spontaneous coupling of AP and RIHP may be of importance in the regulation of salt and water excretion by the pressure diuresis mechanism.

Anesthesia↗
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

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

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↗
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↗
PubMed1986

Active tetraethylammonium uptake across the basolateral membrane of rabbit proximal tubule.

Tetraethylammonium (TEA) uptake was measured in isolated, nonperfused rabbit S2 proximal tubule segments. The TEA cell-to-bath concentration ratio in bicarbonate-Ringer bathing medium was 10-fold higher than that predicted by passive equilibration according to the basolateral electrochemical potential, indicating that TEA uptake is an active process as reported by previous investigators. Removing bicarbonate and CO2 reduced TEA uptake to 22% of control. When bicarbonate-CO2 was replaced by HEPES-O2 or butyrate-O2, TEA uptake was unaltered, but uptake was inhibited when the major buffer anion was omitted. In the presence of 10(-4) M ouabain and bicarbonate-CO2, the TEA cell-to-bath concentration ratio was reduced to 20% of control. TEA uptake in the absence of bicarbonate and CO2 was unaltered by the addition of 10(-4) M ouabain. TEA uptake was inhibited when the bathing medium contained 0 mM K+ or 2 mM Ba2+. These data 1) demonstrate that active basolateral TEA uptake is dependent on medium buffer capacity and 2) support the concept that a portion of TEA uptake occurs via a passive equilibration pathway.

Animals↗
PubMed1986

Lactate oxidation by three segments of the rabbit proximal tubule.

Oxidation of [U14C]lactate to 14CO2 was measured in vitro, in nonperfused anatomically defined segments of rabbit proximal tubule (S1, proximal convoluted, and S2 and S3, proximal straight tubules). The rate of lactate oxidation was similar in S2 and S3 segments, and within the range of lactate oxidation rates measured in vivo. In contrast, the oxidation rate of S1 segments was significantly lower than that of S2 or S3. In proximal straight tubules, lactate oxidation was inhibited by incubation at 0 degrees C, or by application of 1 mM ouabain. To determine if the rate of transepithelial transport affected the rate of lactate oxidation, lactate oxidation was measured in proximal straight tubules after the lumen had been opened by perfusion with Ringer's containing 10 mM polyethylene glycol. No difference in lactate oxidation rate was observed between tubules with patent lumina and nonperfused tubules. These results suggest that the various segments of the renal proximal tubule have different metabolic characteristics, and that the rate of substrate oxidation is related to the activity of the Na+, K+-ATPase.

Absorption↗
PubMed1981

Lactate transport by Thamnophis proximal tubule: sodium dependence.

We examined the effects of experimental conditions on unidirectional lactate fluxes in isolated perfused Thamnophis proximal tubule. Fluxes were determined by adding L(+)-[U-14C]lactate to perfusate or bath as appropriate (lactate concentration = 1 mM). The lumen-to-bath lactate flux (Jlb lact) was not affected by the manipulations required to exchange perfusate or bath or by substitution of phosphate for bicarbonate buffer. During measurement of Jlb lact, lactate was ordinarily added to the perfusate only. However, addition of 1 mM lactate to the bath had no effect on Jlb lact, indicating no role for exchange diffusion in renal lactate absorption. In contrast, substitution of tetramethylammonium (TMA+) or choline for Na+ decreased Jlb lact by about 75%. The bath-to-lumen flux (Jbl lact) was also decreased by TMA+ substitution for Na+, although by only about 25%. From these and previous results we suggest that in Thamnophis proximal tubule, lactate is absorbed by an active Na+-dependent transport process that probably derives its energy from the lumen-to-cell electrochemical gradient for Na+.

Animals↗
PubMed1980

Lactate absorption in Thamnophis proximal tubule: transport versus metabolism.

Proximal tubules from the kidney of Thamnophis (garter snake) were perfused in vitro and unidirectional fluxes of lactate measured using L(+)-[U-14C]lactate, (lactate concentration, 1 mM). The lumen-to-bath (absorptive) flux (Jlb lact) significantly exceeded the bath-to-lumen flux (backflux) (Jbl lact) in each of 12 tubules (seven distal proximal and five proximal proximal). The flux ratio (Jlb lact/Jbl lact) was approximately 3.00. At flow rates of 13-16 nl/min and lactate concentration of 1 mM the net flux was about 1.60 pmol . min-1 . mm-1 in both proximal proximal and distal proximal segments. Both fluxes were decreased by perfusion at 5 degrees C. To determin e the contribution of metabolism of lactate to its absorption, Jlb lact was measured at 25 degrees C in 10 distal proximal tubules during perfusion with [14C]lactate, lactate concentration, 1 mM, and with [methoxy-3H]inulin. In these experiments, the amount of 14C found in the bath was 93% of the amount of 14C absorbed from the lumen. Chromatography showed that all of the 14C found in the bath was [14C]lactate. These data establish that in Thamnophis proximal tubule lactate absorption occurs against an electro chemical gradient by transport of the intact lactate molecule without significant metabolism.

Absorption↗
PubMed1980

Peritubular uptake of lactate by Thamnophis proximal tubule.

Lactate is absorbed in the proximal tubule and also enters tubular cells at the peritubular membrane. To characterize peritubular lactate entry, lactate uptake was measured in isolated nonperfused proximal tubules. Tubules were dissected and incubated in Ringer solution with L(+)-[U-14C]lactate and 3H2O. After incubation, the tubules were extracted, and the extracts were assayed for 14C and 3H or were chromatographed to determine the percentage of tubule 14C identifiable as lactate. Maximal steady-state tubular fluid-to-bath lactate concentration ratios (TF/B lactate) occurred by 30-60 min incubation at 25 degrees C. In 30 min, one-third of the tubules established a TF/B lactate ratio greater than 1.00, and 61.4 +/- 18.6% of tubule 14C was lactate. There was no difference in TF/B lactate ratio in proximal and distal proximal segments. Uptake was depressed at 5 degrees C. Mersalyl at 10(-4) M increased the TF/B lactate ratio and tubule water content. Probenecid at 7.5-30 x 10(-4) M also increased the TF/B lactate ratio. Distal proximal tubules incubated with [3H]PAH showed a control TF/B para-aminohippurate (PAH) ratio of approximately 30, but with 10(-4) M mersalyl the TF/B PAH ratio was approximately 1.00. Lactate uptake at the peritubular membrane occurs against an electrochemical gradient, independently from the PAH transport mechanism.

Animals↗
PubMed1975

Steady-state glucose oxidation by dog kidney in vivo: relation to Na+ reabsorption.

In eight experiments at normal or slightly elevated blood glucose concentration we quantified the steady-state renal glucose oxidation rate (see article) during control, at reduced Naomega absorptive rates (raised ureteral pressure), and during respiratory alkalosis. A tracer amount of either [1-14C]glucose or or [U-14C]D(omega)-glucose was infused at a constant rate into one renal artery. (see article) was calculated from the renal 14CO2 production rate (corrected for recirculation) and the specific activity of glucose in renal arterial blood. The control (see article) (n equals 8) equals 4.40 plus or minus 0.9 mumol/100 g-min (mean plus or minus SE). When net Naomega reabsorption was decreased by 45% (n equals 6), or when the pH of extracellular fluid was raised (n equals 2), no significant effect on (see article) (9.1 plus or minus 4.2 and 3.9 plus or minus 2.3 mumol/min-100 g, respectively) occurred. The mean glucose oxidation rate for all experiments was 5.65 plus or minus 1.73 mumol g-1-min-1 and required similar to 13% of the renal O2 utilization. Glucose oxidation provides energy either for basal renal work or for some portion of renal transport work not affected by increased ureteral pressure.

Alkalosis, Respiratory↗
PubMedDate not supplied

Comparison of the oxidation rates of glucose and lactate in relation to support of Na+ reabsorption.

The renal oxidation rates of glucose and lactate in the dog in vivo, in the dog cortical slice and in the isolated perfused rat kidney were compared. Lactate decarboxylation rate, on a carbon-atom basis, was from 2 to 10 fold greater than that of glucose. In the substrate-limited perfused kidney, glucose replaced only 30-40% of the substrates oxidized in vivo, while lactate replaced up to 80% of the substrates oxidized in vivo. Insulin lack does not account for these differences in the rates of lactate and glucose oxidation. Glucose and lactate support GFR and Na+ reabsorption to approximately the same extent in spite of their different rates of oxidation. Thus Na+ reabsorptive rate: CO2 production rate is not a constant and depends on the substrate being oxidized. The virtual absence of glucose oxidation by the dog cortical slice suggests either that: 1) glucose oxidation supports primarily medullary Na+ reabsorption while lactate oxidation supports cortical Na+ reabsorption as well of 2) glucose oxidation is more selectively coupled to Na+ reabsorptive work than is lactate oxidation.

Animals↗