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Biomedical subjects

G R Marchand

Publications and source records attributed to G R Marchand.

At least 19 recordsLinked to original sources
PubMed1989

Atrial natriuretic factor inhibits adrenergic and purinergic neurotransmission in the rabbit isolated vas deferens.

This study tests the hypothesis that atrial natriuretic factor (ANF) acts to inhibit neurotransmission in the rabbit vas deferens. The vas deferens is a unique model of autonomic neurotransmission in that it is composed of primarily nonvascular smooth muscle and has both a purinergic or twitch contraction and an adrenergic or phasic contraction associated with its response to electrical stimulation. In this study ANF was found to inhibit both adrenergic and purinergic neurotransmission in the rabbit vas deferens. ANF inhibited both the electrically induced phasic contraction and electrically induced norepinephrine release in a concentration-dependent manner over the ANF concentration range of 10(-10) to 10(-7) M. ANF at a concentration of 10(-7) M had no effect on norepinephrine-induced or ATP-induced contractions. Therefore, the neuromodulatory effect of ANF in the rabbit vas deferens appears to be prejunctional, on the release of the neurotransmitters norepinephrine and ATP from the nerve terminal and not postjunctional on the smooth muscle. Neither the alpha-2 antagonist rauwolscine nor the cyclooxygenase inhibitor indomethacin had any effect on the inhibitory effect of ANF on electrically induced twitch or phasic contractions. Additionally, ANF did not affect vasa deferentia prostaglandin E production. Therefore, the inhibitory neuromodulatory ANF effect is not mediated via alpha-2 adrenergic receptors or prostaglandin E production. The observed inhibitory neuromodulatory effects in this study may be involved in the hypotensive effects of ANF including natriuresis, diuresis and vasodilation.

Adenosine Triphosphate↗
PubMed1989

Cyclic guanosine 3',5' monophosphate mediates the inhibitory effect of atrial natriuretic factor in adrenergic, neuronal pheochromocytoma cells.

This study tests the hypothesis that atrial natriuretic factor (ANF) inhibits catecholamine release from rat pheochromocytoma cells by increasing levels of intracellular cyclic GMP (cGMP). Rat differentiated pheochromocytoma cells are a model of adrenergic nerves and allow the exploration of the effects of various hormones, autacoids, drugs and neuromodulators on adrenergic neurotransmission in cell culture. Synthetic rat ANF (99-126) inhibited K+-induced norepinephrine and dopamine release, as measured by high-performance liquid chromatography, in a concentration-dependent manner over the concentration range of 10(-11) to 10(-8) M. ANF stimulated intracellular cGMP accumulation, as measured by specific radioimmunoassay, in a concentration-dependent manner over the same concentration range. The cGMP analog, N2-2'-O-dibutyryl cGMP also inhibited K+-induced norepinephrine and dopamine release in a concentration-dependent manner. The results of this study are consistent with the hypothesis that ANF acts as an inhibitory neuromodulator in adrenergic nerves via the second messenger, cGMP.

Animals↗
PubMed1986

Effect of secretin on glomerular dynamics in dogs.

These studies were performed to determine whether a role for increased renal plasma flow (RPF) in the regulation of glomerular filtration rate (GFR) could be demonstrated in dogs by infusing the polypeptide hormone secretin, a vasodilator that has been reported to increase GFR. Differences between control and recollection periods were compared by paired t test in five time-control dogs (group 1) and 10 secretin dogs (group 2). In group 2, secretin (100 mU . kg-1 . min-1, ia) significantly increased single-nephron glomerular filtration rate (SNGFR) 11.1 +/- 3.1 nl/min (20%) and glomerular plasma flow 59 +/- 11 nl/min (26%). Similar increases in GFR (26%) and RPF (29%) were observed. Secretin also increased glomerular capillary pressure 5.2 +/- 0.8 mmHg and free-flow proximal tubule pressure 5.5 +/- 1.0 mmHg. Secretin did not significantly affect average effective filtration pressure (EFP) but significantly increased the ultrafiltration coefficient (Kf) 0.74 +/- 0.14 nl . min-1 . mmHg-1. These differences were significantly greater than those observed in group 2. It is concluded that secretin increased SNGFR primarily by an effect on Kf. This is consistent with the marked effect that Kf is predicted to have on glomerular filtration in dogs. The maintenance of EFP agrees with other vasodilator studies and indicates that GFR is only moderately dependent on plasma flow in dogs.

Animals↗
PubMed1985

Effect of parathyroid hormone on the determinants of glomerular filtration in dogs.

Elevated levels of parathyroid hormone (PTH) often are associated with reduced glomerular filtration rate (GFR) in humans. Although PTH has been reported to reduce the ultrafiltration coefficient (Kf) in rats, GFR declined only if they were plasma expanded. In contrast, PTH does not reduce GFR in dogs, despite filtration pressure disequilibrium. To evaluate this apparent discrepancy, the determinants of GFR were measured in acutely thyroparathyroidectomized dogs. In the absence (n = 8) and presence (n = 10) of synthetic bovine PTH, GFR was 29 +/- 3 and 26 +/- 2 ml/min; Single nephron glomerular filtration rate was 58 +/- 4 and 51 +/- 3 nl/min; glomerular plasma flow was 248 +/- 22 and 250 +/- 24 nl/min; glomerular capillary pressure was 58 +/- 2 and 61 +/- 3 mmHg; Bowman's space pressure was 19 +/- 2 and 19 +/- 1 mmHg; and systemic oncotic pressure was 19 +/- 0.8 and 18 +/- 0.5 mmHg. Average effective filtration pressure (EFP) was significantly greater in the presence (18.6 +/- 1.3 mmHg) than in the absence (14.6 +/- 0.9 mmHg) of PTH. Therefore, Kf per glomerulus calculated from these data was significantly (P less than 0.01) less in the presence than in the absence of PTH (2.91 +/- 0.29 and 3.98 +/- 0.16 nl X min-1 X mmHg-1, respectively). It is concluded that PTH reduced Kf. Whereas this effect predicts reduced GFR in dogs, given filtration pressure disequilibrium, a concomitant increase in EFP maintained GFR in the present study.

Animals↗
PubMed1977

Stationary microperfusion study of phosphate reabsorption in proximal and distal nephron segments.

Micropuncture studies demonstrate phosphate reabsorption in proximal tubules and between the late proximal and early distal convoluted tubule accessible to micropuncture. To further define the sites of phosphate reabsorption, the stationary microperfusion technique was applied to proximal and distal nephron segments. Phosphate reabsorption was evaluated in superficial loops of proximal tubules, descending segments beyound late proximal tubules accessible to micropuncture, ascending segments up to the point of micropuncture in the distal tubule, and superficial loops of distal tubules of thyroparathyroidectomized rats. Microperfusates of 1.3 or 2.6 nl (100 mmol/1 mannitol, 100 mmol/l NaCL, 32P-phosphate and 3H-inulin) were injected and then withdrawn after contact times of 2--108 s. Phosphate recovery relative to that of inulin was determined. A steep exponential decline of phosphate recovery (R) iwth increasing contact time (t) was observed in the superficial proximal tubule and descending segments. The slopes of the logarithmic regressions (10log R)/t, +/- SEM) were: -1.68 +/- 0.33 and -1.21 +/- 0.24min-1 in superficial proximal tubules and descending segments respectively. In contrast, no significant decline in phosphate recoveries (-0.02 +/- 0.04 and + 0.11 +/- 0.10 min-1) was apparent in the ascending segments and distal tubule. It is concluded that phosphate is reabsorbed in the proximal convoluted tubule and adjacent descending segments of the superficial nephron and that there is no significant phosphate reabsorption in distal convoluted tubules and adjacent ascending segments.

Animals↗
PubMed1977

Phosphaturic effect of furosemide: role of PTH and carbonic anhydrase.

The first objective of this study was to examine the effects of furosemide on renal phosphate excretion in the presence and absence of a constant level of parathyroid hormone (PTH) while extracellular fluid volume was held constant. In the absence of PTH, furosemide did not significantly increase fractional phosphate excretion (FEP%, 4.2 +/- 2.7 to 6.2 +/- 1.9%; five dogs). In the presence of PTH, furosemide increased FEP% from 23.4 +/- 3.7 to 33.8 +/- 6.0% (P less .025; five dogs). Thus, the phosphaturia induced by furosemide was dependent on the presence of PTH. The second objective was to evaluate the hypothesis that furosemide exerts its phosphaturic effect through carbonic anhydrase inhibition, and therefore we tested for additivity of the phosphaturic effect of furosemide, and acetazolamide. In the presence of a constant level of PTH, acetazolamide increased FEP % from 24.5 +/- 1.8% to 40.7 +/- 5.1% P less than .025, five dogs. The subsequent administration of furosemide did not further increase FEP%, delta 3.3 +/- 8.9%; NS. Thus, the phosphaturic effect of furosemide was not additive to that of acetazolamide, indicating that acetazolamide and furosemide may share similar mechanisms for inhibiting phosphate reabsorption.

Acetazolamide↗
PubMed1977

Effect of secretin on renal blood flow, interstitial pressure, and sodium excretion.

Most renal vasodilators are natriuretic. However, secretin increases renal blood flow (RBF) markedly but produces only a very slight increase in sodium excretion (UNaV). To investigate this observation further, the relationship between vasodilatation, interstitial pressure (IP), and UNaV was studied in dogs. Intrarenal infusion of secretin increased RBF (delta=107+/-19 ml/min). The IP, as measured from chronically implanted polyethylene matrix capsules, was not significantly changed (delta=-0.3+/-0.5 mmHg). UNaV was slightly, although significantly, increased (delta=19+/-4 mueq/min). Following a similar increase in RBF with an intrarenal infusion of acetylcholine (ACh), IP and UNaV increased markedly (delta=8.2+/-0.8 mmHg and 174+/-23 mueq/min, respectively). Neither secretin nor ACh) altered glomerular filtration rate or blood pressure. Both secretin and ACh produced comparable increases in peritubule capillary(delta=5+/-1 and 7.5+/-1.4 mmHg, respectively) and free-flow tubule pressure (delta=7+/-2 and 9.5+/-1.4 mmHg, respectively). In summary, the usual relationship between vasodilatation and IP was dissociated during secretin infusion, whereas the relationship between IP and natriuresis was not dissociated.

Acetylcholine↗
PubMed1977

Regulation of filtration rate in sodium-depleted and -expanded dogs.

Sodium balance may affect the response of single-nephron filtration rate (SNFR) to changes in renal arterial pressure (deltaRAP) when the SNFR is measured in the absence of orthograde fluid delivery from the proximal tubule. This thesis was tested in sodium-depleted and -expanded dogs given furosemide, Doca, and low- or high-salt diets, respectively. After 7 days of treatment, renal renin content was significantly greater in the sodium-depleted group (delta = 23.5 +/- 7.4 DU [dog units]/g kidney). Glomerular filtration rate and renal plasma flow were similar in both groups following changes in RAP of 29 +/- 4 and 29 +/- 3 mmHg in the sodium-depleted and -expanded groups, respectively. SNFR at high RAP was not different from SNFR at low RAP in the sodium-depleted group (delta = -0.2 +/- 4.9 nl/min) and slightly, but significantly, greater in the sodium-expanded group (delta = 7.6 +/- 2;1 nl/min). However, the response of SNFR was similar to that of whole-kidney filtration rate. Furthermore, the autoregulatory response (deltaSNFR/deltaRAP) was not significantly different between the groups but was significantly greater than the response calculated for RAP below the range studied. It is concluded that an autoregulatory response of SNFR, in the absence of orthograde fluid delivery from the proximal tubule, is observed in both sodium-depleted and -expanded dogs.

Animals↗
PubMed1977

Phosphate transport in superficial and deep nephrons in phosphate-loaded rats.

We tested the hypothesis that greater phosphate delivery from deep nephrons than from superficial nephrons contributes to the addition of phosphate to the collecting system during phosphate loading. In the first group of eight anesthetized Munich-Wistar rats infused with phosphate and parathyroid hormone (PTH), fractional delivery of phosphate (FDP%) from superficial distal tubules was 56 +/- 6%, significantly less than the amount appearing in the urine, 67 +/- 6% (P less than 0.01). In the second group of six rats, we determined whether this addition of phosphate could be accounted for by a higher FDP% from the deep nephrons. Free-flow micropuncture collections were taken from deep nephrons (ascending limb of the loop of Henle in the papilla), superficial nephrons (distal tubules in the cortex), and urine (duct of Bellini). The FDP% to the ascending limb of the loop of Henle in deep nephrons was 78 +/- 10%, significantly greater than to the distal convoluted tubules in superficial nephrons, 51 +/- 6% (P less than 0.005), and the fractional excretion of phosphate in urine, 72 +/- 10% (P less than 0.05). Although a difference between FDP% in superficial and deep nephrons due to reabsorption in the ascending limb of the loop of Henle cannot be ruled out from the present data, other studies indicate that this interpretation is unlikely. We conclude that greater phosphate delivery by deep nephrons contributes to the addition of phosphate to the collecting system of phosphate-loaded rats.

Animals↗
PubMed1977

Filtration dynamics in dogs: glomerular capillary pressure.

Hydrostatic pressure in the glomerular capillaries, the primary driving force for glomerular ultrafiltration, is directly measurable only in those species with glomeruli present on the capsular surface of the kidney. Accordingly, this crucial measurement must be made indirectly in species not so endowed, such as the dog. Several different methods have been utilized in the dog; unfortunately each is indirect. This review deals with an assessment of the following methods for the determination of glomerular capillary pressure in dogs: a) reduction of arterial pressure method; b) ureteral occlusion method; c) the Winton or venous occlusion method; d) fraction of arterial pressure method; e) back calculation from forces opposing filtration; f) sieving method; and g) single nephron occlusion of the Gertz stop-flow method. Recent studies in the dog, utilizing single nephron occlusion techniques, provide estimates of glomerular capillary pressures of approximately 60 mn Hg in the autoregulatory range of blood pressure.

Animals↗
PubMed1976

Ethacrynic acid induced release of prostaglandin E to increase renal blood flow.

Ethacrynic acid administered to anesthetized dogs was found to increase the level of prostaglandin E as determined by radioimmunoassay in renal venous blood at the time when renal blood flow was increased by this agent. No change was found in the renal venous level of prostaglandin F. When ethacrynic acid was administered after treatment with indomethacin, which blocks the increase in renal blood flow induced by the natriuretic agent, no increase in the renal venous level of prostaglandin E was seen. Thus, the dilation of the renal vasculature would appear to be caused by a stimulation of synthesis and release of prostaglandin E by ethacrynic acid.

Animals↗
PubMed1976

Intrarenal calcium in phosphate handling.

The intrarenal role of plasma ionized calcium (Ca), on fractional phosphate excretion (FE PO4) was investigated in dogs with control of parathyroid hormone (PTH). In series 1, acute thyroparathyroidectomy was immediately followed by a constant infusion of bovine PTH (0.01 U/kg per min). Subsequent calcium chloride infusions increased Cai in plasma phosphate and decreased in the percentage of ultrafiltrable phosphate. A 20% increase in Cai significantly increased FE PO4 by +3.82 +/- 0.97% (P less than 0.01) when infused intravenously and by +2.62 +/- 1.06% (P less than 0.05) when infused in the renal artery. In contrast, a 75% increase in Cai did not significantly change FE PO4. In series 2, dogs were thyroparathyroidectomized 18 h before experiments, and no PTH infusion was initiated. A bolus of bovine PTH (30 U/kg) increased FE PO4 + 8.9 +/- 0.9% (P less than 0.001) in hypocalcemic dogs, +19.1 +/- 4.4% (P less than 0.001) in normolcalcemic dogs, and +15.5 +/- 1.5% (P less than 0.001) in hypercalcemic dogs. We conclude that increases in plasma calcium potentiate the phosphaturic effect of PTH. This potentiating effect is attenuated in marked hypercalcemia by superimposed hemodynamic and/or metabolic changes.

Animals↗
PubMed1976

Sodium balance and the natriuresis of hypertonic saline infusion in dogs.

Recently, a paradoxical effect of dietary salt intake on the natriuresis following hypertonic saline infusion was observed in rats. In these experiments the effects of alterations in dietary sodium on the natriuretic response to a hypertonic saline load was studied in dogs. Dogs maintained on a high-sodium diet did not have a significantly different natriuresis than those on a low-sodium diet. When differences in sodium balance were amplified by the use of deoxycorticosterone, furosemide, and manipulation of dietary sodium, dogs in positive sodium balance showed a significantly enhanced initial excretion of sodium followed by a reversal of the pattern. Consequently, the cumulative sodium excretion was not different between low- and high-sodium groups. Since the cumulative natriuretic response to isotonic saline infusion was larger in dogs in positive sodium balance compared to those in negative sodium balance, the failure to detect a difference following hypertonic saline infusion was probably because of the increased plasma sodium concentration.

Animals↗