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Biomedical subjects

C Baylis

Publications and source records attributed to C Baylis.

At least 109 records · Page 6Linked to original sources

Glomerular filtration and volume regulation in gravid animal models.

The gestational increase in glomerular filtration rate (GFR) that occurs in the normal rat is the result exclusively of an increase in plasma flow rate, and there is no sustained increase in glomerular capillary blood pressure during a normal pregnancy. The factor or factors that initiate the gestational renal vasodilatation (and plasma volume expansion) are maternal, not fetoplacental in origin. Apart from ruling out prostaglandins as an initiating agent, animal studies have not yet defined the precise nature of the initiating factors; it is unlikely that the gestational plasma volume expansion can be the sole cause of the increased GFR seen in pregnancy. The normal kidney in pregnancy exhibits substantial renal reserve to amino acid infusion, despite being already vasodilated by the gestational stimulus. The renal volume-sensing and control system of tubuloglomerular feedback is fully operative in pregnancy, and appears to be 'reset' to perceive the expanded plasma volume of pregnancy as normal. This observation agrees with many other indications that the sensors perceiving and controlling intravascular volume are reset during a normal pregnancy to enable the mother to accommodate the increased plasma volume without provoking a natriuretic response. Multiple pregnancies do not have any cumulative, long-term deleterious effects on renal function, either when the underlying function is normal or when it has been compromised by removal of renal mass plus high-protein feeding. In the short-term, pregnancy does not worsen kidney function when underlying glomerulonephritis is present. Therefore, the hyperfiltration of pregnancy does not appear to be a damaging entity, unlike other hyperfiltration states studied in the male rat. Still unknown is the mechanism by which pregnancy does worsen underlying glomerular disease in some women. The preliminary data in the rat, presented above, suggest that the exacerbating influence may be something other than the glomerular haemodynamic changes of pregnancy.

Animals↗

Renal effects of cyclooxygenase inhibition in the pregnant rat.

Experiments were performed to investigate the effects of acute cyclooxygenase inhibition on renal hemodynamics in mid and late pregnant rats. In micropuncture studies in the control state, midterm pregnant rats exhibited increased single-nephron glomerular rate (SNGFR) and no change in glomerular or arterial blood pressures. In late pregnancy, SNGFR was no longer significantly elevated, glomerular pressure was similar, and arterial pressure was depressed compared with the virgin. Cyclooxygenase inhibition led to significant increases in single-nephron and whole-kidney filtration and flow in mid and late pregnant rats. This effect was also seen in the virgin control group, and all groups involved a selective renal vasodilation without change in blood pressure. In the absence of anesthesia and surgical stress, cyclooxygenase inhibition had little effect in virgin or pregnant chronically catheterized rats. These studies indicate that the cyclooxygenase-dependent arachidonic acid metabolites are not the agents directly responsible for the gestational rise in the glomerular filtration rate.

Animals↗

Head-down tilt and restraint on renal function and glomerular dynamics in the rat.

A model utilizing 25 degree head-down tilt (HDT) and incorporated with chronic catheterization and renal micropuncture techniques in rats was employed to study alterations in renal function induced by HDT. Renal function and extracellular volume measurements were performed after 24 h, 4 days, and 7 days of HDT in conscious rats and compared with their own control measurements and to nontilted but similarly restrained rats. After 24 h HDT, glomerular filtration rate (GFR) increased 19 +/- 8% and renal plasma flow (RPF) increased 18 +/- 8% with increases in urine flow rate, Na+, and K+ excretion in conscious rats. These increases after 24 h were associated with an increase in extracellular volume of 16 +/- 3% (P less than 0.01). In the nontilted controls, there was a decrease in extracellular volume after 24 h of suspension. After 7 days of HDT, GFR was decreased by 7 +/- 1% (P less than 0.01), but RPF and extracellular fluid volume were not different from control values. However, RPF and GFR increased in the nontilted rats after 7 days. After 7 days of HDT renal micropuncture studies demonstrated that single-nephron filtration rate was also decreased from 43 +/- 2 to 31 +/- 3 nl/min (P less than 0.05) due solely to reductions in the glomerular ultrafiltration coefficient (0.11 +/- 0.01 to 0.07 +/- 0.01 nl.s-1 X mmHg-1, P less than 0.05). There was a dissociation between GFR and water and Na+ excretion at days 4 and 7 of HDT not observed in the nontilt restraint controls.

Absorption↗

Effects of administered thromboxanes on the intact, normal rat kidney.

The effects of administered thromboxanes on the intact, normal rat kidney were studied. Euvolemic male rats received intraarterial infusions of thromboxane B2 (TXB2) and the stable thromboxane A2 analog (U46619) and the effects on renal function were investigated, using glomerular micropuncture and whole-kidney clearance techniques. Both TXB2 and U46619 were renal vasoconstrictors and lowered GFR by reducing renal plasma flow rate; U46619 was much more potent that TXB2. Neither agent caused any marked change in the glomerular capillary ultrafiltration coefficient (Kf). Thus in the rat, the thromboxanes reduce filtration rate by increasing renal vascular resistance and without exerting a marked influence on Kf.

Animals↗

Hormone profiles for progesterone, oestradiol, prolactin, plasma renin activity, aldosterone and corticosterone during pregnancy and pseudopregnancy in two strains of rat: correlation with renal studies.

Plasma samples were obtained throughout pregnancy and pseudopregnancy from Sprague-Dawley (SD) rats and during pregnancy from rats of the Munich Wistar (MW) strain. The concentrations of progesterone, oestradiol, prolactin, plasma renin activity (PRA), aldosterone and corticosterone were measured by radioimmunoassay to establish hormonal profiles in the two strains of rat. Circulating progesterone concentrations in both strains of rat were significantly higher during pregnancy than in virgin controls, except at term in the SD group. The hormonal pattern for pseudopregnancy was similar to that of the first half of pregnancy. Oestradiol concentrations were similar to, or lower than, those in virgin controls throughout pseudopregnancy and for the first 2 weeks of pregnancy in both strains of rat. Increased concentrations of steroid were seen only in the pregnant groups towards term. In SD rats, highest prolactin concentrations were apparent during the first half of pregnancy and pseudopregnancy, and at term in the pregnant group. Pregnant MW rats showed a different profile for this hormone, with low levels throughout pregnancy except at term. In all groups PRA rose to a peak at day 9 and decreased to day 16. Pregnant SD rats also showed a significant increase at term. Aldosterone concentrations were significantly increased at several stages of pregnancy in both strains of rat, particularly during the second half of gestation. Pseudopregnant animals showed a different hormone profile, with no significant changes until day 16 when lower concentrations were recorded. There was little variation in the circulating corticosterone concentration except in pregnant rats at term when levels fell. These findings are discussed in relation to the known renal changes of pregnancy and pseudopregnancy.

Aldosterone↗

Angiotensin II inhibition on blood pressure and renal hemodynamics in pregnant rats.

Late-pregnant (18-20 days) and virgin rats were studied under anesthesia or while awake to investigate the effect of acute angiotensin II (ANG II) inhibition (with saralasin or captopril) on mean arterial blood pressure (AP) and renal hemodynamics. ANG II inhibition had no effect on AP in either anesthetized or awake virgin rats. Saralasin produced no effect on renal hemodynamics although with captopril small increases in renal plasma flow rate (RPF) and decreases in renal vascular resistance (RVR) occurred in virgins. In anesthetized pregnant rats, ANG II inhibition evoked marked decreases in AP. In some rats receiving saralasin, AP was only mildly depressed and RVR fell, leading to increases in glomerular filtration rate and RPF. In others, saralasin produced large decreases in AP, and indices of renal function became unmeasurable because of near cessation of urine flow. All late-pregnant anesthetized rats receiving captopril showed increased RPF irrespective of the magnitude of the fall in AP. In awake pregnant rats no effect on AP was seen with ANG II inhibition. Saralasin had no effect on renal hemodynamics although with captopril a small increase in RPF was observed. These data indicate that the stress of acute surgery and anesthesia produces a dependence of AP on ANG II in the pregnant but not the virgin rat. Under normal pregnant (awake) conditions, however, ANG II inhibition has no net effect on AP.

Angiotensin II↗

Effect of intermittent feeding on renal hemodynamics in conscious rats.

The hemodynamic influences of many forms of dietary restriction have not been studied in the conscious rat. To examine the effect of one regimen of dietary restriction, alternate-day feeding, on renal hemodynamics, we performed 56 clearance studies in 20 unanesthetized, previously catheterized male Sprague-Dawley rats at mean age 30 wk. Group 1 rats (n = 10) were given standard chow only on alternate days for 25 wk and then studied after feeding and after fasting days, whereas group 2 rats (n = 10) were fed ad libitum during the same period and then studied randomly. In group 1, glomerular filtration rate (GFR, clearance of inulin) and renal blood flow [RBF, clearance of PAH/(1 - hematocrit)] increased 23 and 19%, respectively, after feeding days compared with fasting days (GFR, 4.25 vs. 3.47 ml/min, P less than 0.005; RBF, 22.2 vs. 18.6 ml/min, P less than 0.025). After feeding, mean arterial pressure and plasma protein concentration were unchanged, hematocrit increased slightly, and fractional excretion of sodium rose from 0.23 to 0.57%. Both GFR and RBF averaged 31% less in group 1 than in group 2 but, when factored by body weight, the differences were abolished. The results indicate that alternate-day feeding causes substantial oscillations in GFR and RBF in healthy awake rats through mechanisms unlikely to involve changes in extracellular fluid volume alone and limits GFR and RBF to average values markedly lower than those observed for larger ad libitum-fed rats of the same age.

Animals↗

Renal hemodynamics and glomerular morphology in repetitively pregnant aging rats.

Measurements were made of renal and glomerular hemodynamics and glomerular morphology in repetitively pregnant and age-matched virgin female Munich-Wistar rats. Repetitive pregnancies and lactation provide a stimulus to chronic increases in glomerular filtration rate (GFR) and these rats were studied, by micropuncture, approximately 4 to 6 weeks after the end of the fifth gestation/lactation cycle. No differences were seen in GFR or renal plasma flow (RPF) rate nor in any of the determinants of single nephron filtration rate (SNGFR) in repetitively pregnant compared to virgin rats, although SNGFR itself was slightly but significantly elevated in repetitively pregnant rats. There was no evidence of systemic hypertension, proteinuria, or abnormal glomerular morphology in either group despite their advanced age (approximately 42 to 46 weeks). Thus, the moderate chronic increase in GFR due to the stimulus of repetitive pregnancy and lactation does not lead to eventual deterioration in renal function or structural abnormalities.

Aging↗

Tubuloglomerular feedback activity in virgin and 12-day-pregnant rats.

Tubuloglomerular feedback activity was evaluated by micropuncture and microperfusion techniques in virgin and 12-day-pregnant Munich-Wistar rats. Plasma volume increases in pregnancy, which could suppress feedback activity, thus contributing to the rise in glomerular filtration rate observed in normal midterm pregnancy. Late proximal tubules were microperfused at 0, 10, 20, and 40 nl/min and the resulting filtration rate in the same nephron was evaluated. Nephron filtration rate (SNGFR) in proximal and distal tubules of other nephrons was also measured to assess the degree of activation of the tubuloglomerular feedback system and the relation of the spontaneous (normal) late proximal flow rate and SNGFR (distal tubule collections). SNGFR decreased significantly (from the 0 nl/min perfusion value) when late proximal tubules were perfused at 20 and 40 nl/min in both virgin and 12-day-pregnant rats. Tubuloglomerular feedback activity was not suppressed in pregnancy, but the relationship between SNGFR and late proximal tubule perfusion rate was reset for a higher value for SNGFR. The difference between proximal and distal SNGFR suggests that the feedback system was more activated in the virgin than in the pregnant rat. Thus, in spite of the known increases in plasma volume that occur in pregnancy, the kidney does not sense this volume expansion as a stimulus to suppress feedback activity.

Animals↗

Effects of chronic prolactin administration on renal hemodynamics in the rat.

Experiments were performed to measure the systemic and renal hemodynamic effects of chronic PRL administration to female rats (in which pseudopregnancy was induced) and male rats. Studies were performed in rats of the Munich-Wistar and Sprague-Dawley strains. In micropuncture studies under anesthesia, no differences were seen in plasma volumes or whole kidney or glomerular hemodynamics in PRL-injected rats compared to those sham-injected controls regardless of sex. In separate studies, observations were made in conscious, chronically catheterized female rats of the Sprague-Dawley strain. Neither the glomerular filtration rate nor the renal plasma flow rate was different on day 9 of PRL-induced pseudopregnancy compared to values in the control state in the same animals. Thus, PRL-induced pseudopregnancy does not cause increases in glomerular filtration rate, renal plasma flow rate, or single nephron GFR or its determinants, whereas in previous studies on pseudopregnancy resulting from a sterile mating, increases in glomerular and renal hemodynamics occurred which were indistinguishable from those seen during the first half of pregnancy in the rat. These data suggest that PRL is not involved directly in either the plasma volume expansion or increase in renal hemodynamics that occurs after mating in the rat.

Animals↗

A micropuncture and renal clearance study in the rat of the urinary excretion of heparin, chondroitin sulphate and metabolic breakdown products of connective tissue proteoglycans.

Commercial heparin and acid glycosaminoglycans (AGAG) prepared from normal female human urine were tritiated catalytically in aqueous solution. Nasal septal chondroitin sulphate was tritiated by NaB3H4 reduction of the aldehydes produced by very limited periodate oxidation. The refined products were characterized by electrophoresis and biochemical analysis. The tritiated products were infused into Munich-Wistar rats, and their kidney clearances were measured and compared with that of inulin. The passage of heparin and chondroitin sulphate at the glomerulus was restricted, as shown by the ratios of their concentrations in Bowman's space fluid and plasma. Comparison with whole kidney urine/plasma ratios indicated that some tubular reabsorption also occurred. The low whole kidney clearance of AGAG from normal female human urine probably also resulted from restricted glomerular passage and tubular reabsorption. The low whole kidney clearances, primarily caused by restricted transglomerular movement, are discussed on the bases of (a) the molecular sizes and shapes of the AGAG, (b) an electrostatic barrier at the basement membrane and (c) binding of AGAG to plasma colloids, thus reducing plasma levels of free AGAG. The implications of these findings in (a) heparin therapy and (b) urinalysis of disorders of connective tissue metabolism are discussed.

Animals↗

Renal and systemic hemodynamic responses to intravenous infusion of leukotriene C4 in the rat.

We studied the systemic and renal hemodynamic effects of leukotriene C4 (2 micrograms/kg per min for 5 minutes, iv) in the rat. During the period of its infusion, leukotriene C4 produced a significant elevation of mean arterial pressure and reductions in cardiac output and renal blood flow, as measured by electromagnetic flow probes. These effects were abolished by FPL55712 , a putative antagonist of sulfidopeptide leukotrienes, but not by saralasin or indomethacin. Leukotriene C4 also resulted in an average loss of 20% in plasma volume which, during the postinfusion period, perpetuated the low cardiac output state and thus provoked the release of angiotensin II. This vasoactive peptide sustained the elevation in systemic vascular resistance and the reduction in renal blood flow over a 70-minute postinfusion observation period. Consequently, glomerular filtration rate fell by approximately 50%. These angiotensin II-mediated effects were abolished by saralasin. Indomethacin prevented the leukotriene C4-induced loss of plasma volume and, thus, allowed for the significant recovery of cardiac output and renal blood flow during the post-infusion period, thereby preserving glomerular filtration rate. We conclude that leukotriene C4 exerts direct systemic and renal vasoconstrictor, as well as cardiodepressant effects, during the period of its infusion. By virtue of its vasopermeability enhancing effect, leukotriene C4 also results in an immediate loss of plasma volume, an effect which requires the presence of secondarily generated cyclooxygenase products and which perpetuates the hemodynamic abnormalities observed beyond the period of leukotriene C4 infusion.

Animals↗

Glomerular ultrafiltration in the pseudopregnant rat.

Whole kidney and single nephron indices of glomerular ultrafiltration were measured by clearance and micropuncture techniques in anesthetized virgin, 9-day pregnant, and 9-day pseudopregnant Munich-Wistar rats. Whole kidney glomerular filtration rate (GFR) and single nephron glomerular filtration rate (SNGFR) were elevated in pregnant and pseudopregnant rats compared with virgins (0.78 +/- 0.05, 0.75 +/- 0.06 vs. 0.57 +/- 0.03 ml/min, P less than 0.005 and P less than 0.001; 32.1 +/- 2.5, 30.0 +/- 2.8 vs. 22.1 +/- 2.0 nl/min, P less than 0.01 and P less than 0.05, respectively). Total renal plasma flow rate (RPF) and single glomerular plasma flow rate (QA) were also increased in pregnant and pseudopregnant rats compared to virgins (3.05 +/- 0.19, 2.90 +2- 0.24 vs. 2.28 +/- 0.21 ml/min, P less than 0.01 and P less than 0.05; 109.0 +/- 15.8, 100.4 +/- 12.8 vs. 68.0 +/- 6.9 nl/min, both P less thn 0.05). There was little difference in the other determinants of ultrafiltration among the three groups. Plasma volume was measured in separate experiments and was higher in pregnant and pseudopregnant rats compared with virgins (9.4 +/- 0.2, 9.8 +/- 0.4 vs. 8.4 +/- 0.3 ml, P less than 0.01 and P less than 0.05, respectively). The gestational increase in GFR in the rat occurs as the result of increased RPF, which is due to both plasma volume expansion and renal vasodilation. Since the changes in renal hemodynamics seen in pseudopregnancy were almost identical to those occurring in pregnant rats, the early stimulus to increased GFR must be maternal and not fetoplacental in origin.

Animals↗

The mechanism of the increase in glomerular filtration rate in the twelve-day pregnant rat.

1. Whole kidney and micropuncture techniques were employed to investigate the determinants of glomerular ultrafiltration in virgin and 12-day pregnant rats. 2. A significant increase in whole kidney glomerular filtration rate (g.f.r.) and superficial cortical single nephron g.f.r. was noted in pregnant rats compared to virgins. 3. Increases in whole kidney and glomerular plasma flow rate also occurred in pregnancy which were in proportion to the increase in rate of filtration. No differences were noted in the hydrostatic and oncotic pressures which influence formation of glomerular ultrafiltrate in the superficial nephron population. 4. Reduction in arterial haematocrit and no change in mean red cell volume indicate that a plasma volume expansion has occurred by day 12 of pregnancy in the rat. 5. It is concluded that the increased g.f.r. seen in 12-day pregnant rats is exclusively the result of an increase in renal plasma flow rate (r.p.f.) since the other determinants of glomerular ultrafiltration are unaffected by pregnancy. The plasma volume expansion which also occurs must be, at least in part, responsible for the increase in r.p.f.

Animals↗