Biomedical subjects

C Baylis

Publications and source records attributed to C Baylis.

At least 91 records · Page 5Linked to original sources

PubMed1991

Hemodynamic responses to acute volume expansion in Dahl salt-sensitive rats.

The purpose of this study is to evaluate hemodynamic responses to acute volume expansion in chronically instrumented, conscious Dahl salt-sensitive (Dahl-S) and Dahl salt-resistant (Dahl-R) rats that have been maintained on either 0.45% NaCl, 1% NaCl, or 7% NaCl (5 days) intakes. Total peripheral resistance (TPR), but not arterial pressure, was increased by 5 days of 7% NaCl in Dahl-S (P less than 0.05) but not in Dahl-R. In Dahl-S, but not in Dahl-R, right atrial pressure increased with increasing dietary NaCl (P less than 0.05). On the 0.45% NaCl intake, atrial pressure did not differ in the two strains, whereas on both the 1 and 7% NaCl diets atrial pressure was higher in Dahl-S than in Dahl-R (P less than 0.05). In response to acute extracellular fluid volume expansion, arterial pressure did not change, and cardiac output increased in Dahl-S and in Dahl-R. On the 0.45% NaCl intake, TPR decreased (P less than 0.01) similarly in response to volume expansion in both strains; however, on the 1% NaCl intake TPR decreased in Dahl-R (P less than 0.05) but not in Dahl-S. In contrast, in animals fed 7% NaCl for 5 days, TPR decreased acutely in Dahl-S (P less than 0.01) but not in Dahl-R. These observations suggest that cardiopulmonary baroreflex activity is impaired in Dahl-S on a 1% NaCl intake, possibly as a consequence of elevated right atrial pressure. This alteration of the cardiopulmonary baroreflex may contribute to increased TPR in Dahl-S on a high-NaCl intake.

Animals↗

PubMed1991

Short term natriuretic responses in the conscious Zucker obese rat.

Renal clearance studies were conducted in conscious, chronically catheterized obese and lean Zucker rats to investigate the natriuretic responses to i) acute IV infusion of isotonic NaCl = 5% of total body weight and ii) IV infusion of alpha rat atrial natriuretic peptide (ANP) in a dose of 300 ng/kg/min. In the baseline state, arterial blood pressure (BP) was significantly higher in obese vs lean rats. Absolute values of GFR and sodium excretion were similar but lower in obese vs lean rats when factored for body weight. In the 2 h period during and after NaCl infusion, obese rats showed a greater natriuresis vs lean while BP rose significantly and similarly. ANP infusion was natriuretic in obese rats but had no effect on lean rats. ANP lowered BP in both groups but BP remained higher in obese vs lean rats at all times. These studies show that in the chronic, unstressed preparation the 6-8 month old, female Zucker obese rat has a higher BP vs the 6-8 month old lean Zucker. The short term natriuretic response to either a NaCl load or ANP infusion is greater in obese vs lean Zuckers and the depressor response to ANP is intact in obese Zuckers. Thus the higher BP in this model of obesity is unlikely to be due to either a defective response to ANP or to a defect in the renal response to acute sodium challenge.

Animals↗

PubMed1990

Renal effects of administered atrial natriuretic peptide in the conscious, aging rat.

Studies were performed in conscious, chronically catheterized male Sprague-Dawley rats to investigate the effect of administered atrial natriuretic peptide (ANP) on blood pressure, renal hemodynamics and urinary electrolyte excretion. Studies were performed on young adult (3-4 month old) rats and on aging rats (18-24 months of age). Low dose ANP (80 ng/kg/min for 60 min) had no effects on renal hemodynamics in either young or old rats and produced only a slight blood pressure reduction in young animals. No effect on urinary electrolyte excretion was evident in young rats whereas in the old animals, low dose ANP produced large rises in the rate of sodium excretion, fractional excretion of sodium and urine flow rate. A four fold higher dose of ANP evoked a moderate natriuretic and a marked antihypertensive response in young rats. Time control studies indicated that time alone had no influence on urinary sodium excretion rate, the fractional excretion of sodium or urine flow rate. These studies indicate a much enhanced sensitivity to the natriuretic effects of administered ANP by the kidneys of old rats.

Aging↗

PubMed1990

Renal vasodilatory response to intravenous glycine in the aging rat kidney.

Studies were performed in the awake, chronically catheterized male Sprague-Dawley rat to investigate renal hemodynamics in the baseline state and also in response to a large intravenous (IV) amino acid (glycine) load. Studies were performed in young adult rats (age 3 to 4 months), old rats (age 18 months), and senescent rats (age 22 to 24 months). Histologic evaluation of the kidney permitted a correlation between structural and functional changes with aging. Histology showed progressive glomerular damage (sclerosis) with aging. In 18-month-old rats, the glomerular filtration rate (GFR) was normal, which, considering the level of glomerular injury (only 64% normal glomeruli), must indicate heterogeneity of glomerular function, with some hyperfunctioning glomeruli. By 22 to 24 months of age (at which time approximately 50% mortality has occurred in males of this strain), GFR is substantially reduced, as is renal plasma flow rate (RPF). Severe glomerular damage was observed histologically (only 34% normal glomeruli), indicating widespread heterogeneity of glomerular function. Young adult rats displayed a substantial renal vasodilation in response to acute IV glycine infusion, which resulted in approximately 25% increases in GFR and RPF. The renal vascular responsivity to glycine was diminished at 18 months and was completely absent in 22- to 24-month-old rats. This altered renal vasodilatory response to glycine probably reflects both structural changes associated with aging and also the compensatory vasodilation of intact hyperfunctioning remnant nephrons as other nephrons are lost due to aging.

Aging↗

PubMed1990

Renal effects of moderate hemorrhage in the conscious pregnant rat.

Studies were performed in conscious, chronically catheterized virgin, 8- to 9-day-pregnant, and 15- to 16-day-pregnant Sprague-Dawley rats in baseline state and after removal of 7.5% total blood volume. Measurements were made of glomerular filtration rate (GFR), renal plasma flow (RPF), renal vascular resistance (RVR), arterial blood pressure (AP), and urinary electrolyte excretion. In baseline state, GFR and RPF were elevated at days 8-9 and days 15-16 of pregnancy (vs. virgins) due to a gestational renal vasodilation. The fall in hematocrit indicates substantial plasma volume expansion by days 15-16 of pregnancy. After removal of 7.5% total blood volume, little change occurred in AP in any group. However, the renal vasculature provided a sensitive response to moderate hemorrhage, since RPF fell and RVR increased similarly in virgin, 8- to 9-day- and 15- to 16-day-pregnant rats. GFR was protected in virgin and 8- to 9-day-pregnant rats but fell significantly in late pregnancy. Urinary electrolyte excretion tended to fall but was not significantly reduced by hemorrhage in any group. These studies indicate that renal vascular response to moderate hemorrhage is similar in virgin, early, and late pregnancy. Thus effector mechanisms that sense volume and regulate RVR must be continually reset to respond to progressive plasma volume expansion of pregnancy as normal.

Animals↗

PubMed1990

Endothelial derived relaxing factor controls renal hemodynamics in the normal rat kidney.

These studies were conducted in the conscious, chronically catheterized rat to determine whether the endothelial derived relaxing factor (EDRF) controls renal function in the normal state. Administration of the EDRF synthesis inhibitors N-monomethyl-L-arginine (NMA; 100 mg/kg body weight) or N-nitro-L-arginine methylester (NAME; 10 mg/kg body wt) led to a large, sustained rise in blood pressure, a large rise in renal vascular resistance, a fall in renal plasma flow, a relatively slight reduction in glomerular filtration rate, and a consequent rise in filtration fraction. In addition, a marked natriuresis occurred because of a reduction in the fractional reabsorption of sodium. In separate studies, a continuous infusion of excess L-arginine (300 mg/kg body wt bolus followed by 50 mg/kg body wt per min) attenuated the NMA- or NAME-induced rise in blood pressure and reversed the renal hemodynamic effects such that a significant rise in renal plasma flow was seen. L-Arginine alone produced a selective renal vasodilation and large increases in sodium excretion. These observations support earlier suggestions that tonic release of EDRF controls the basal blood pressure and also show that renal function in the normal unstressed rat is markedly influenced by EDRF. These studies suggest that, in addition to controlling renal plasma flow, EDRF may have other, complex actions at the glomerulus. The natriuresis seen after acute inhibition of EDRF with NMA or NAME was probably the result of a pressure natriuretic response to the abrupt rise in blood pressure and also, perhaps, reflects removal of an EDRF influence to directly enhance sodium reabsorption somewhere in the nephron.

Animals↗

PubMed1990

Glucocorticoids and control of glomerular filtration rate.

Glucocorticoids given acutely or chronically at physiological/pharmacological doses increase GFR in both experimental animals and humans. Glomerular micropuncture studies have shown that in the normal rat kidney, glucocorticoids vasodilate both the preglomerular and efferent resistances and result in an increase in glomerular plasma flow, which is the sole factor responsible for the increase in GFR. However, the mechanism(s) initiating these alterations in the glomerular microcirculation remain obscure. The glucocorticoid-induced increase in GFR does not appear to be due to volume expansion or alteration in tubulo-glomerular feedback activity. Chronic glucocorticoid administration has been shown to increase renal prostaglandin synthesis in some but not all species; however, a link between increased prostaglandin production and glucocorticoid-induced increase in GFR has not been established. A number of studies have examined glucocorticoid-induced alterations in renal vascular reactivity to vasoconstrictor agonists and the data have been conflicting. The suggestion that glucocorticoid-stimulated ANP production evokes the increase in GFR is unlikely to be correct based on substantial differences in the glomerular hemodynamic changes seen with ANP or glucocorticoids. An interesting proposal that appears well worth exploring is that glucocorticoids may increase GFR through their effects on catabolism of proteins to increase production of amino acids. Amino acid infusion markedly elevates GFR and has a similar glomerular hemodynamic profile as that of glucocorticoids. By virtue of their action to increase GFR, glucocorticoids increase the rate of electrolyte and water delivery into the nephron. Therefore, glucocorticoid-induced alterations in electrolyte and water excretion may be secondary to an elevation in GFR, in addition to direct actions of glucocorticoids on the tubule. Also, by determining the hemodynamic state of the kidney, and hence, rate of fluid delivery through the nephron, glucocorticoids may influence the sensitivity of the nephron to regulatory influences. Glucocorticoids have their most profound effect (especially clinically) by modifying the immunological or cellular mechanisms responsible for glomerular injury. Less important is their ability to increase GFR. In view of some evidence that suggests increasing glomerular pressure accelerates the progression of established renal disease, some might speculate that glucocorticoids actually increase glomerular damage under certain conditions.

Animals↗

PubMed1989

Differences between the sexes and the effects of surgery and anesthesia on the urinary excretion rate of eicosinoids in the rat.

Measurements were made of PGE2, PGF2 and TXB2 in the urine of male and female Munich-Wistar rats. Initial urine were collected in the awake state in metabolic cages and were followed by collections of ureteral urine during surgery and anesthesia both before and during cyclooxygenase inhibition with indomethacin. The excretion rate of all eicosinoids in the awake state was similar between the sexes. PGE2 excretion remained unaffected after anesthesia/surgery in both sexes indicating that providing plasma volume is maintained, the PGE2 system is not activated by the stress of anesthesia/surgery. Near complete inhibition of PGE2 was observed during indomethacin administration in both sexes. TXB2 excretion rates rose in both males and females with anesthesia/surgery and were slightly suppressed during indomethacin in males only. PGF2 excretion rose following surgery/anesthesia and was statistically significant in female rats. During indomethacin, TXB2 excretion was moderately reduced in male rats and unaffected in the female. Near complete inhibition of PGF2 was observed during indomethacin in both sexes. The urinary eicosinoid responses to indomethacin seen in these studies failed to provide an explanation for our earlier observations of a fall in renal vascular resistance in the female rat, studied under anesthesia and during indomethacin administration.

Anesthesia↗

PubMed1989

Sex and the single kidney.

Micropuncture measurements revealed that approximately 9 to 10 months after uninephrectomy and maintenance on a high-protein diet, glomerular capillary BP was significantly higher in male than in virgin female rats. This might account for the greater susceptibility of the male to age- and ablation-induced glomerular damage reported by others, although at the time of the present studies, significant reduction in function and worsening in glomerulosclerosis in males v females was barely evident. In a second group of chronically uninephrectomized females, the effects of multiple (five) consecutive pregnancies and lactations were investigated and did not indicate any severe deleterious long-term effects of pregnancy on the glomeruli in this model of underlying renal compromise. Variable responses to an acute intravenous glycine challenge which did not correlate well with the extent of glomerular damage were observed in each group, suggesting that this test may not always be informative regarding underlying glomerular disease.

Animals↗

PubMed1989

Gentamicin-induced glomerulotoxicity in the pregnant rat.

Ten daily injections of gentamicin, 40 mg/kg/d intraperitoneal (IP), produced a marked reduction in the glomerular capillary ultrafiltration coefficient (Kf) of virgin female Munich-Wistar rats without eliciting significant reductions in glomerular filtration rate (GFR) or single nephron (SN)GFR. A similar gentamicin-induced decrease in Kf was seen in midterm pregnant (day 12) rats and the normal gestational increase in GFR and SNGFR was blunted by gentamicin. Concomitant converting enzyme inhibition (CEI) (MK 421, 50 mg/L drinking water) completely prevented the gentamicin-induced decrease in Kf in virgin females, thus confirming that the gentamicin-induced decline in Kf is mediated by angiotensin II (ANG II). These studies indicate that pregnancy neither exacerbates nor ameliorates gentamicin-induced glomerulotoxicity and also that glomerular ANG II responsivity is not diminished in midterm pregnant rats.

Acute Kidney Injury↗

PubMed1989

Immediate and long-term effects of pregnancy on glomerular function in the SHR.

Micropuncture experiments investigated 1) whether a gestational renal vasodilation occurs in the hypertensive gravida and 2) whether pregnancy exposes the spontaneously hypertensive rat (SHR) kidney to increased glomerular blood pressures and thus ultimately to glomerular injury. These studies demonstrate that there is no gestational vasodilation in the midterm pregnant SHR (renal vascular resistance, 30 +/- 2 vs. 30 +/- 3 (mmHg.ml-1.min in midterm pregnant vs. virgin SHR) and, of importance, no difference in glomerular blood pressure in pregnant vs. virgins (54 +/- 1 vs. 55 +/- 1 mmHg). In the long term after three repetitive pregnancies there is no worsening in glomerular function compared with age-matched virgin SHRs (single nephron glomerular filtration rate, 26 +/- 2 vs. 23 +/- 1 nl/min), perhaps not surprising in view of the lack of change in glomerular hemodynamics during a pregnancy. Additional observations indicated that the midterm pregnant, repetitively pregnant, and virgin SHRs have no vasodilatory response to an intravenous amino acid load. Thus the SHR has no acute renal vasodilatory reserve to a glycine infusion and is also unable to undergo a gestational vasodilation. This has no negative impact on either mother or babies and may actually be beneficial to the long-term health of the maternal kidney.

Animals↗

PubMed1989

Glomerular effects of pregnancy in a model of glomerulonephritis in the rat.

These studies were designed to investigate the functional and morphologic glomerular effects of pregnancy in a model of experimentally induced glomerulonephritis (GN) in the Munich-Wistar rat. Virgin and midterm (day 12) pregnant rats were studied during the autologous phase of anti-glomerular basement membrane antibody GN and were compared with normal control virgin and pregnant rats. In this model of moderately intense GN, glomerular filtration rate (GFR) and single-nephron GFR were not different from normal controls; however, glomerular micropuncture revealed that glomerular capillary blood pressure was elevated and the glomerular capillary ultrafiltration coefficient, Kfi, was reduced in rats with GN compared with normal rats. In addition a substantial proteinuria was present, and there was morphologic evidence of a moderate and fairly uniform GN. The superimposition of pregnancy to midterm (11 to 13 days) had no effects on the proteinuria or glomerular morphology in rats with GN. Also, pregnancy did not further alter the increased glomerular blood pressure or reduced Kf that occur in this model of GN. Despite the presence of an underlying glomerular disease, the maternal kidney was able to increase renal plasma flow. When underlying mild GN is present, 11 to 13 days of pregnancy does not appear to worsen the disease in the short term. Other studies are needed to determine the long-term renal effects of repeated pregnancy when underlying GN is present.

Animals↗

PubMed1988

The mechanisms of proteinuria in aging rats.

Aging is associated with the appearance of a selective proteinuria which cannot be attributed to any specific underlying renal disease. The present studies were conducted in conscious, chronically catheterized young (3-4 months), non-proteinuric male rats and old (22-25 months), proteinuric males to determine the mechanism(s) of the proteinuria. Compared with young males, old proteinuric rats had increased blood pressure, reduced glomerular filtration rate (GFR) and renal plasma flow and heavy proteinuria. Fractional clearance of neutral dextran (D) and anionic dextran sulfate (DS) were both significantly increased at the 36 A molecular radius in old rats; the increase in DS fractional clearance being greater than the increase in D fractional clearance. The proteinuria of aging is therefore due to moderate increases in glomerular permeability and, more importantly, to loss of fixed glomerular polyanion. Striking glomerular morphologic changes were also evident in the old rats including thickening of the glomerular basement membrane and extensive glomerular sclerosis.

Aging↗

PubMed1988

Glomerular and tubular handling of differently charged human immunoglobulin light chains by the rat kidney.

1. To examine the effect of charge and molecular size on the renal handling of immunoglobulin light chain, three different human light chains were purified, iodinated and characterized with regard to molecular weight and isoelectric point. The molecular weights were similar, whereas the isoelectric points ranged from markedly cationic to markedly anionic. 2. Renal handling of the light chains was determined in vivo in the Munich-Wistar rat and in vitro in the isolated perfused rat kidney. 3. Significant restriction to the transglomerular passage of all three light chains was evident in the intact kidney, with the most anionic light chain being restricted most while the cationic light chain was restricted least. The charge dependence of filtration of these naturally occurring proteins was, however, much less pronounced than has previously been reported for the synthetic dextrans. 4. Tubular reabsorption of the three light chains was quite variable in the intact kidney and did not appear to be related to molecular charge. In the isolated perfused kidney, once account had been taken of the abnormally high rate of filtration of these proteins, the reabsorption of the three light chains was strikingly similar to that seen in vivo. 5. With these three purified human light chains no marked influence of charge (pI) has been demonstrated in vivo or in vitro, for glomerular restriction or renal tubular reabsorption. Some other properties of human myeloma light chains may determine their renal handling and nephrotoxicity.

Absorption↗

PubMed1988

Sex differences in renal hemodynamics in rats.

These studies were designed to investigate sex differences in renal hemodynamics under control conditions and in response to two different cyclooxygenase inhibitors. Studies were performed under anesthesia in males, females, and ovariectomized (OVX) rats and in separate groups of conscious, chronically catheterized male and female rats of a different strain. In the control periods, before cyclooxygenase inhibition, the male kidney was vasodilated relative to the female. Because male and female rats have the same number of glomeruli per kidney, the total vascular resistance per glomerulus is substantially greater in females than males. Cyclooxygenase inhibition in the anesthetized intact female rat produced significant increases in single-nephron glomerular filtration rate, glomerular plasma flow rate, glomerular filtration rate, and renal plasma flow, whereas afferent and efferent arteriolar resistances and renal vascular resistance fell. In contrast, anesthetized male and OVX female rats showed no renal hemodynamic response to cyclooxygenase inhibition. In the absence of anesthesia and recent surgery, intact awake female rats responded similarly to conscious male rats in that neither showed any response to cyclooxygenase inhibition. These data suggest a functional sex difference in both baseline renal hemodynamics and the renal response to cyclooxygenase inhibition, the latter unveiled by surgical stress.

Animals↗

PubMed1988

Effect of amino acid infusion as an index of renal vasodilatory capacity in pregnant rats.

Experiments were performed in midterm pregnant and virgin Munich-Wistar rats to investigate how the chronically vasodilated kidney of a gravid animal would respond to a further acute vasodilatory stimulus, in the form of a 90-min intravenous infusion of the amino acid glycine (at 0.167 mmol.kg-1.min-1). In young adult midterm pregnant rats studied in the base-line state, glomerular filtration rate (GFR), single-nephron GFR, renal plasma flow (RPF), and glomerular plasma flow were significantly greater (by approximately 30%) than in virgins due to a gestational renal vasodilation. Despite the underlying chronic renal vasodilation of pregnancy, the kidney of the gravid rat displays a marked further renal vasodilation (with consequent further increases in GFR and RPF) in response to acute glycine loading; the percent increase in GFR and RPF was similar to that seen in the relatively vasoconstricted virgin. This ability to further acutely increase the GFR in the pregnant rat was not limited to animals maintained on a normal protein diet but was also seen in older pregnant rats subjected to the additional chronic vasodilatory stimulus of long-term high-protein feeding, although in these older animals the gestational vasodilation was blunted.

Amino Acids↗

PubMed1987

The determinants of renal hemodynamics in pregnancy.

Studies in the rat have permitted a complete characterization of the glomerular hemodynamic changes that occur during a normal pregnancy. The rise in glomerular filtration rate (GFR) is the result of an evenly distributed increase in plasma flow to all nephrons due to vasodilation of both pre- and postglomerular resistance vessels. Pregnancy is not associated with any change in blood pressure in the glomerular capillaries; neither is there any detectable alteration in the glomerular water permeability or filtration surface area. Despite the chronically maintained renal vasodilation of pregnancy, gravid rats exhibit substantial renal reserve when challenged with an amino acid load, indicating that a residual renal vasodilatory capacity exists in the kidney of the normal pregnant animal. Despite the concomitant plasma volume expansion of pregnancy, the tubuloglomerular feedback system (a volume regulatory system that modulates GFR) remains fully active in the pregnant rat, suggesting that the plasma volume in pregnancy is not sensed as expanded by this system. The factor(s) that initiates the gestational rise in GFR is currently unknown, although since similar renal hemodynamic changes occur in the pseudopregnant rat, the stimulus is maternal rather than fetoplacental in origin.

Amino Acids↗

PubMed1987

Renal disease in gravid animal models.

Micropuncture studies in the rat have indicated that in the short term, the superimposition of pregnancy on an experimentally induced, advanced, autologous phase glomerulonephritis (GN) does not lead to any worsening of the functional or morphological changes characteristic of this disease. Indeed, pregnant rats with GN exhibit a tendency toward higher GFR and plasma flow rate than do virgin rats with this disease. In chronic studies to investigate the long-term effects on kidney function of pregnancy, normal rats undergoing five closely spaced pregnancies and lactations exhibit glomerular hemodynamics, 24-hour protein excretions, and morphology similar to those of age-matched virgins. When repetitive pregnancies are superimposed on rats with the long-term hyperfiltration stimuli of uninephrectomy plus high dietary protein feeding, no worsening of the proteinuria occurs in comparison to virgin rats subjected to the same degree of renal ablation plus high protein. Although filtration and plasma flow rates are lower in these repetitively pregnant rats as compared with virgin rats, amino acid infusion revealed substantial renal reserve in the repetitively pregnant rats. These studies show that gestational hyperfiltration does not, in and of itself, provide an adverse stimulus to the maternal kidney.

Animals↗