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Biomedical subjects

L L Woods

Publications and source records attributed to L L Woods.

At least 19 recordsLinked to original sources
PubMed2001

Hypertension after neonatal uninephrectomy in rats precedes glomerular damage.

The present study was designed to determine whether adult hypertension caused by a reduced number of nephrons from birth is due to preceding glomerular damage. Newborn male Sprague-Dawley rat pups were uninephrectomized during the first 24 hours after birth (UNX rats). At 20 weeks of age, chronically instrumented UNX animals were hypertensive on a normal-sodium (0.20%) diet compared with sham-operated controls (142+/-2 versus 124+/-2 mm Hg in controls). Body weights and the total kidney-to-body weight ratio were not significantly different in adult UNX animals compared with controls. Glomerular filtration rate (GFR) was reduced by 49% in UNX rats (1.85+/-0.24 versus 3.65+/-0.22 mL/min). Urine protein excretions were higher in UNX rats (20+/-2 versus 7+/-1 mg/d in controls). On a high-sodium (3.15%) diet, arterial pressure increased more in UNX than in controls (28+/-9 versus 3+/-1 mm Hg). In contrast, in animals studied at 8 weeks of age, GFR was only reduced by 26% in UNX animals (2.02+/-0.06 versus 2.73+/-0.07 mL/min). Their hypertension (125+/-2 versus 117+/-2 mm Hg) was also salt sensitive (increase on high-sodium diet of 35+/-11 versus 8+/-2 mm Hg in controls) but was not associated with proteinuria or histological signs of glomerular disease. Number of glomeruli per kidney in UNX animals was not different from controls, but individual glomerular volume increased by 41%. Thus, surgical removal of 50% of the nephrons, when done during development, causes reduced renal function and salt-sensitive hypertension in adulthood. Hypertension is present earlier in life than signs of glomerular disease, which suggests that hypertension is a major contributor to rather than primarily resulting from onset of renal disease.

Analysis of Variance↗
PubMed2001

Maternal protein restriction suppresses the newborn renin-angiotensin system and programs adult hypertension in rats.

Restriction of maternal protein intake during rat pregnancy produces offspring that are hypertensive in adulthood, but the mechanisms are not well understood. Our purpose was to determine whether this adult hypertension could be programmed during development by suppression of the fetal/newborn renin-angiotensin system (RAS) and a consequent reduction in nephron number. Pregnant rats were fed a normal protein (19%, NP) or low-protein (8.5%, LP) diet throughout gestation. Birth weight was reduced by 13% (p < 0.0005), and the kidney/body weight ratio was reduced in LP pups. Renal renin mRNA levels were significantly reduced in newborn LP pups; renal renin concentration and renin immunostaining were suppressed. Renal tissue angiotensin II levels were also suppressed in newborn LP (0.079 +/- 0.002 ng/mg, LP versus 0.146 +/- 0.016 ng/mg, NP, p < 0.01). Mean arterial pressure in conscious, chronically instrumented adult offspring (21 wk) was higher in LP (135 +/- 1 mm Hg, LP versus 126 +/- 1 mm Hg, NP, p < 0.00007), and GFR normalized to kidney weight was reduced in LP (p < 0.04). The number of glomeruli per kidney was lower in adult LP offspring (21,567 +/- 1,694, LP versus 28,917 +/- 2,342, NP, p < 0.03), and individual glomerular volume was higher (1.81 +/- 0.16 10(6) microm(3), LP versus 1.11 +/- 0.10 10(6) microm(3), NP, p < 0.005); the total volume of all glomeruli per kidney was not significantly different. Thus, perinatal protein restriction in the rat suppresses the newborn intrarenal RAS and leads to a reduced number of glomeruli, glomerular enlargement, and hypertension in the adult.

Animals↗
PubMed2000

Fetal origins of adult hypertension: a renal mechanism?

It is well-recognized that the etiology of cardiovascular disease includes at least two components: a genetic component and a 'lifestyle' or environmental component. However, epidemiological evidence accumulating over the past decade has provided an increasingly strong case for the important involvement of a third component, that of environmental conditions during development (i.e. before birth), in contributing to an individual's overall cardiovascular risk. Factors in the prenatal environment to which a baby is exposed can cause permanent changes in the structure and function of specific tissues in the body. Although perhaps valuable in the short term in that they allow survival until birth, these changes are maladaptive in the long term because they predispose the individual to an array of adult diseases. Experimental data elucidating the possible physiological and morphological mechanisms by which this perinatal 'programming' for adult cardiovascular disease occurs are only just now becoming available. However, it appears that the renin-angiotensin system, and the important role it plays in renal development, may be central in setting the trajectory that leads to cardiovascular disease, and in particular hypertension.

Adult↗
PubMed1999

Novel high-performance liquid chromatographic and solid-phase extraction methods for quantitating methadone and its metabolite in spiked human urine.

A novel solid-phase extraction (SPE) method and HPLC method were developed for the determination of methadone and its metabolite from spiked human urine. For sample cleanup, a spiked urine sample was pretreated with phosphoric acid followed by a well-thought-out SPE method using a 10-mg Oasis HLB 96-well extraction plate. In this SPE method, the concentration of methanol as well as the pH are optimized to preferentially isolate the analytes of interest from the sample matrix. Low elution volumes (200 microl) are achieved; this eliminates evaporation and reconstitution of the sample solution. Recoveries from human urine matrix were greater than 91% with RSD values less than 4.5%. For the HPLC analysis, the separation was obtained using a SymmetryShield RP18 column with a mobile phase of 0.1% TFA-methanol (60:40, v/v). Good peak shapes were obtained without the need of addition of any competing reagent to the mobile phase. Additionally, significant signal-to-noise enrichment was achieved by diluting the final SPE eluates four-fold with water.

Chromatography, High Pressure Liquid↗
PubMed1999

Neonatal uninephrectomy causes hypertension in adult rats.

This study was designed to test the hypothesis that a reduced number of nephrons from birth leads to increased arterial pressure in adulthood. Newborn Sprague-Dawley rat pups were uninephrectomized during the first 24 h after birth. In chronically instrumented adult animals (approximately 22 wk), mean arterial pressure on a normal (0.20%)-Na+ diet was higher in uninephrectomized rats (133 +/- 2 mmHg vs. 121 +/- 2 mmHg in controls, P < 0.0001). Body weights were not significantly different, but the total kidney-to-body weight ratio was significantly reduced by 14% in adult uninephrectomized animals (P < 0.05). Glomerular filtration rate was reduced by approximately 30% in uninephrectomized rats (1.84 +/- 0.09 vs. 2.63 +/- 0.14 ml/min, P < 0.0002), and effective renal plasma flow was reduced to a lesser degree (6.37 +/- 0.38 vs. 7.87 +/- 0.51 ml/min, P < 0.03), such that the filtration fraction was also reduced (0.291 +/- 0.007 vs. 0.338 +/- 0.014, P < 0.01). After 7-10 days on a high (3.15%)-Na+ diet, arterial pressure increased more in uninephrectomized animals than in controls (20 +/- 3 vs. 1 +/- 1 mmHg, P < 0.003). Thus surgical removal of 50% of the nephrons, when done during development, caused reduced renal function and a salt-sensitive hypertension in adulthood. These data suggest that a reduced nephron endowment from birth, caused by genetic and/or perinatal environmental factors, could contribute to essential hypertension in adulthood.

Aging↗
PubMed1999

Cardiorenal destiny: the role of genes and environmental factors.

For many years, it has been known that genes and environmental factors interact to determine an individual's blood pressure. The purpose of this article is twofold. First, the authors review current molecular genetic approaches to delineating genes that lead to the development of hypertension, focussing on the renin-angiotensin system. We then consider perinatal environmental factors that impact adult blood pressure. Epidemiologic data suggest that good maternal nutritional status is essential to avoid programming individuals for future health problems as adults. One factor that appears to play an important role in programming for hypertension in adulthood is maternal dietary protein restriction during pregnancy, possibly by suppression of the fetal renin-angiotensin system and consequent impairment of renal development. The association between lower birthweight and increased adult blood pressure, established in epidemiologic studies, may be caused by suboptimal maternal diet or placental insufficiency, resulting in transient changes in fetal hormone systems or gene expression that permanently alter the structure and function of the kidney and vasculature.

Adult↗
PubMed1998

Perinatal ANG II programs adult blood pressure, glomerular number, and renal function in rats.

ANG II is known to be important in normal renal development, but the long-term consequences of a suppressed renin-angiotensin system (RAS) during the developmental period are not completely understood. This study tested the hypothesis that the RAS in the developing animal is important in long-term regulation of renal function and arterial pressure. Newborn Sprague-Dawley rat pups were given the ANG II AT1 receptor antagonist losartan (25 mg . kg-1 . day-1 sc) for the first 12 days of postnatal life (Los). Body weights at weaning (22 days) were significantly reduced in Los (53.4 +/- 3.2 vs. 64.5 +/- 3.6 g in controls); however, at the time of study (approximately 22 wk), body weights and the kidney-to-body weight ratios were not different. In chronically instrumented conscious animals, glomerular filtration rate and effective renal plasma flow were reduced by 27 and 20%, respectively, in Los; the filtration fraction was not different. Maximal urine concentrating ability was also reduced in Los (1,351 +/- 45 vs. 2,393 +/- 52 mosmol/kg in controls). Mean arterial pressure was significantly higher in Los (134 +/- 3 vs. 120 +/- 1 mmHg). The number of glomeruli per kidney was reduced by 42% in Los, but the total glomerular volume was unchanged. Thus perinatal blockade of ANG II AT1 receptors results in fewer but enlarged glomeruli, reduced renal function, and an increased arterial pressure in adulthood. These data indicate that perinatal ANG II, acting via AT1 receptors, plays an important role in renal development and long-term control of renal function and arterial pressure. Physiological conditions that cause suppression of the RAS in the developing animal may have long-term consequences for renal function and blood pressure.

Aging↗
PubMed1996

Renal responses to amino acids in the sheep fetus.

Adult animals and humans are known to increase renal blood flow and glomerular filtration rate (GFR) in response to an acute protein load or amino acid infusion; however, the ontogeny of this phenomenon is not known. This study was designed to test the hypothesis that, despite normally high baseline amino acid levels in the fetus, increases in plasma amino acids stimulate increases in GFR before birth. Eight chronically instrumented fetal sheep (126 +/- 1 days gestation) were infused with a mixture of amino acids (0.15 and 0.30 mmol . kg-1 . min-1 i.v.). Plasma alpha-amino nitrogen levels increased significantly from 7.1 +/- 0.3 to 13.0 +/- 0.9 and 25.5 +/- 2.1 mg/dl, respectively, in response to the two doses, and GFR increased significantly from 3.2 +/- 0.4 to 4.0 +/- 0.5 and 4.6 +/- 0.5 ml/min, respectively. Arterial pressure did not change. Renal amino acid reabsorption was significantly increased at all time points during the amino acid infusion, reaching a value nearly five times that of control by the last clearance period. Na+ reabsorption was also increased throughout the infusion. Na+, K+, and Cl- excretions increased significantly only at the very last time point. These data indicate that the mechanism or mechanisms responsible for amino acid-induced hyperfiltration are present and functional even before birth in the sheep. Because maternal eating patterns and protein intake are known to change maternal plasma amino acid levels and amino acids are actively transported across the placenta, our findings suggest that both acute and chronic changes in maternal protein intake may alter fetal renal function.

Absorption↗
PubMed1995

Role of endogenous atrial natriuretic peptide in chronic anemia in the ovine fetus: effects of a non-peptide antagonist for atrial natriuretic peptide receptor.

Chronic fetal anemia causes polyhydramnios and fetal hydrops and is associated with increased fetal diuresis and natriuresis. To determine the role of atrial natriuretic peptide (ANP) in the renal adaptation to chronic fetal anemia we studied the effects of HS-142-1 (HS), a specific inhibitor of the guanylate cyclase-linked ANP receptor (ANP-GC), in two groups of chronically instrumented unanesthetized sheep fetuses. Seven fetuses were made anemic by serial isovolemic hemorrhage over 1 wk, and five fetuses served as nonanemic controls. Over the 7 d of hemorrhage ANP concentrations increased (45 +/- 7 to 234 +/- 15 fmol/mL). Hematocrit and arterial blood oxygen content were significantly lower in the anemic compared with the nonanemic fetuses (13.8 +/- 0.7 versus 34.6 +/- 2.3% and 0.7 +/- 0.1 versus 2.6 +/- 0.2 mmol/L). Before HS urine flow rate, urinary sodium excretion, fractional excretion of sodium, and renal blood flow were increased in the anemic fetuses, and the extracellular fluid volume (inulin space) was increased (674 +/- 94 versus 497 +/- 71 mL/kg). However, GFR was not different between the groups. HS caused a significant increase in the central venous pressure of the anemic fetuses (0.49 +/- 0.03 to 0.70 +/- 0.05 kPa). Urinary excretion of cGMP was considered to be a marker of endogenous ANP renal effect and was measured before and after a single bolus of HS (5.2 +/- 0.30 mg/kg). HS decreased urinary cGMP excretion to 50 and 37% of baseline levels in anemic and nonanemic fetuses, respectively. Urine flow decreased in both nonanemic and anemic fetuses (0.48 +/- 0.13 to 0.25 +/- 0.06 and 1.30 +/- 0.66 +/- 0.06 mL/min). Sodium excretion decreased in both groups after HS (19 +/- 5 to 9 +/- 2 and 83 +/- 16 to 39 +/- 5 mumol/min). GFR decreased after HS (3.0 +/- 0.8 to 2.4 +/- 0.5 and 3.6 +/- 0.3 to 2.6 +/- 0.2 mL/min. Fraction excretion of sodium also decreased in both groups after HS (4.6 +/- 2.7 to 2.7 +/- 0.5 and 16.1 +/- 2.4 to 11 +/- 1.6). Percent decreases in urine flow, sodium excretion, GFR, and fractional excretion of sodium observed in the anemic fetuses were not statistically different from the nonanemic fetuses. Urine flow and sodium excretion did not decrease to control levels after HS, suggesting that factors in addition to ANP contribute to the natriuresis seen with chronic anemia. After HS a transient increase in renal blood flow was observed in the nonanemic fetuses. An immediate and sustained further increase in renal blood flow was observed in the anemic fetuses (336 +/- 37 to 436 +/- 58 mL/min/100 g of kidney). Decreasing GFR and increasing renal blood flow suggests HS may alter the renal microcirculation by reversing ANP-induced constriction of the glomerular efferent arteriole. We conclude that sustained increases of the central venous pressure suggest that ANP inhibition results in decreased fluid movement into perivascular tissue. Endogenous ANP may help to maintain basal renal function in the normal fetal kidney and participates in the renal adaptation to chronic fetal anemia. ANP may promote urine flow and sodium excretion by its effects on both the renal microcirculation and the sodium reabsorptive capacity of the nephron.

Anemia↗
PubMed1995

Intrarenal mechanisms of renal reserve.

Acute ingestion of protein and intravenous infusion of amino acids are known to stimulate increases in renal blood flow and glomerular filtration rate (GFR) in animals and humans. Although some investigators believe that these changes are mediated by a circulating hormonal factor, there is considerable evidence that intrinsic intrarenal mechanisms such as tubular transport of amino acids and sodium, and the tubuloglomerular feedback mechanism, are involved in this renal hemodynamic response, and that extrarenal factors may not be required.

Amino Acids↗
PubMed1995

Renal reserve in pregnancy.

Normal pregnancy is associated with increases in renal blood flow and glomerular filtration rate, increases that are probably the most dramatic seen under any physiological conditions. Yet, despite these marked elevations in baseline values, most investigators have found that the kidneys of pregnant animals and humans are capable of further vasodilation and hyperfiltration in response to an acute protein load or amino acid infusion, ie, renal reserve is maintained in pregnancy.

Animals↗
PubMed1994

Intralesional implant for treatment of primary oral malignant melanoma in dogs.

The feasibility, safety, and efficacy of a new method of local, sustained-release chemotherapy by use of intralesional cisplatin implants were evaluated in the treatment of oral malignant melanoma. The implant is an injectable viscous gel composed of a protein carrier matrix, a vasoactive modifier, and a chemotherapeutic drug. Twenty dogs with biopsy-proven melanomas were treated at 1- to 2-week intervals by injection with cisplatin implant. Tumors were treated until they resolved or were judged to be unresponsive. In 3 dogs with tumors unresponsive to cisplatin implants, methotrexate implants were used, and in 2 of these dogs, carmustine implants followed the methotrexate. Tumor responses were evaluated by sequential measurements. Melanomas in 14 (70%) of 20 dogs had a > 50% decrease in volume, and in 11 (55%) of these dogs, had a complete response. Tumors with complete responses received a mean cisplatin dose of 11.7 +/- 1.8 mg, delivered in a mean of 2.6 treatments. Two of the dogs with complete response also were treated with methotrexate and carmustine. Implants were well tolerated. Local necrosis, limited to the treatment site, developed in most tumors (17/20) and was associated with tumor response. Systemic toxicosis was minimal; renal insufficiency after cisplatin implants was not evident. Median survival times of dogs with complete tumor response (51 weeks) was substantially greater than that of dogs without local tumor control (10.5 weeks). Recursive partitioning analysis of variables indicated that mandibular tumors of short duration were associated with a positive outcome.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Renal function during chronic anemia in the ovine fetus.

Our purpose was to determine how prolonged anemia alters fetal renal function and acid-base balance. In seven ovine fetuses made progressively anemic over 1 wk by serial isovolemic hemorrhage, hematocrit was reduced from 33.3 +/- 4.5 to 14.0 +/- 1.0%. Femoral arterial oxygen content was less and renal plasma flow was greater in anemic fetuses (1.5 +/- 0.1 ml/dl and 339 +/- 58 ml.min-1.100 g kidney-1) than in 6 control fetuses (7.0 +/- 1.3 ml/dl and 160 +/- 34 ml.min-1.100 g kidney-1). Urine flow and sodium excretion were also greater in anemic fetuses (1.2 +/- 0.6 ml/min and 79 +/- 49.5 mumol/min) than in controls (0.5 +/- 0.2 ml/min and 16 +/- 9.8 mumol/min). This higher sodium excretion was apparently due to a lower fractional sodium reabsorption in anemic fetuses compared with controls (84.1 +/- 5.8 vs. 96.5 +/- 1.7%), rather than to differences in either glomerular filtration rate or amount of filtered sodium. In addition, the higher sodium excretion in anemic fetuses was associated with greater urinary lactate and inorganic phosphate excretions and larger amniotic fluid volumes than in controls. From these data we conclude that when fetal renal oxygen delivery is limited by a prolonged reduction in hematocrit, excretions of sodium and water, as well as other osmotically active solutes, increase, and this results in an increase in amniotic fluid volume.

Amniotic Fluid↗
PubMed1993

Regulation of renal hemodynamics after protein feeding: effects of proximal and distal diuretics.

The purpose of these studies was to compare the effects of proximally and distally acting diuretics on the renal hemodynamic response to protein feeding to determine the importance of the proximal tubule in postprandial renal vasodilation. In chronically instrumented conscious dogs, a meat meal (10 g/kg raw beef) caused glomerular filtration rate (GFR) to increase from 63 +/- 5 to 87 +/- 10 ml/min and effective renal plasma flow (ERPF) to increase from 189 +/- 20 to 249 +/- 20 ml/min, while plasma alpha-amino nitrogen levels rose from 4.0 +/- 0.1 to 6.8 +/- 0.4 mg/dl. Administration of amiloride (0.2 mg/kg + 0.003 mg.kg-1.min-1) or potassium canrenoate (1.76 mg/kg + 1.76 mg.kg-1.h-1), diuretics that act in the distal tubule, had no effect on the renal hemodynamic responses to a meat meal. However, the normal renal hemodynamic responses to protein feeding were abolished during administration of a diuretic that acts in the proximal tubule, acetazolamide (20 mg/kg + 20 mg.kg-1.h-1), although plasma alpha-amino nitrogen levels increased after the meat meal in all experiments. These data suggest that normal proximal tubular sodium reabsorptive function is necessary for acute protein-stimulated renal vasodilation and are consistent with the hypothesis that a tubuloglomerular feedback mechanism may mediate postprandial renal vasodilation.

Acetazolamide↗
PubMed1993

Role of angiotensin II and prostaglandins in the regulation of uteroplacental blood flow.

This study was designed to determine the importance of the renin-angiotensin (RAS) and prostaglandin (PG) systems in regulating uteroplacental blood flow (UBF). Our objectives were to determine: 1) whether angiotensin II (ANG II) acts as a vasodilator or purely as a vasoconstrictor in the uteroplacental circulation, and 2) whether this circulation is capable of autoregulation. In chronically instrumented pregnant dogs (41-54 days gestation), ANG II was infused intravenously at increasing doses (8, 16, and 24 ng.kg-1 x min-1). Arterial pressure rose from 108 +/- 6 to 146 +/- 4 mmHg and UBF did not change but uterine vascular resistance (UVR) progressively increased. When the experiment was repeated while servo-controlling uterine arterial pressure, UBF fell at all doses, reaching 62 +/- 7% of control at the highest dose, and UVR increased as before. Meclofenamate (6 mg/kg i.v.) did not alter the dose-response curves. In separate experiments, uterine perfusion pressure was reduced in steps to 55 mmHg. UBF was well autoregulated down to approximately 85 mmHg, and neither captopril (14 micrograms.kg-1 x min-1) nor meclofenamate altered UBF autoregulation. Thus ANG II appears to act as a vasoconstrictor in the uteroplacental circulation and any preservation of UBF during ANG II appears to be due to the increased arterial pressure. Also, in the dog the uteroplacental circulation possesses a mild to moderate degree of autoregulatory capability, which does not appear to be dependent on the RAS or PGs.

Angiotensin II↗
PubMed1993

Mechanisms of renal vasodilation after protein feeding: role of the renin-angiotensin system.

These studies were designed to determine the importance of the renin-angiotensin system (RAS) in the renal hemodynamic response to acute protein feeding. In chronically instrumented conscious dogs on a normal (80 meq/day) sodium intake, a 10 g/kg meal of raw beef caused glomerular filtration rate (GFR) to increase from 68 +/- 6 to 86 +/- 6 ml/min and effective renal plasma flow (ERPF) to increase from 211 +/- 14 to 263 +/- 15 ml/min. Plasma renin activity (PRA) was 0.44 +/- 0.14 ng ANG I.ml-1 x h-1 and did not change significantly. When the protocol was repeated during infusion of captopril, GFR increased from 67 +/- 11 to 97 +/- 10 ml/min, and ERPF rose from 264 +/- 74 to 392 +/- 82 ml/min after the meat meal. The dogs were then placed on a low-salt diet (approximately 7 meq/day) to physiologically activate the RAS. In sodium-restricted dogs, GFR increased from 71 +/- 7 to 104 +/- 10 ml/min and ERPF increased from 226 +/- 15 to 299 +/- 21 ml/min after the meat meal. PRA was 3.1 +/- 1.0 ng ANG I.ml-1 x h-1 and did not change. Thus neither blockade of the RAS with captopril nor activation of the RAS by salt restriction reduced the renal hemodynamic response to a meat meal. These data indicate that the RAS is relatively unimportant in the renal hemodynamic response to acute protein feeding.

Angiotensin II↗
PubMed1992

Control of renal hemodynamics after protein feeding: role of calcium channels.

This study was designed to test the hypothesis that the changes in renal hemodynamics that occur after a high-protein meal involve voltage-dependent calcium channels. In chronically instrumented female dogs, a 10-g/kg meal of raw beef caused plasma alpha-amino nitrogen levels to increase from 3.9 +/- 0.2 to 6.7 +/- 0.5 mg/dl after 90 min, and glomerular filtration rate (GFR) rose from 59 +/- 6 to 85 +/- 7 ml/min, effective renal plasma flow (ERPF) rose from 130 +/- 22 to 213 +/- 36 ml/min, and sodium excretion rose from 21 +/- 4 to 84 +/- 20 mu eq/min. On another day the dogs were pretreated with verapamil (0.075 mg/kg + 0.005 mg.kg-1.min-1 iv), which did not change arterial pressure significantly but increased GFR by 25 +/- 7% and ERPF by 23 +/- 5%. After a subsequent meat meal, plasma alpha-amino nitrogen increased from 4.0 +/- 0.3 to 6.6 +/- 0.1 mg/dl but GFR, ERPF, and sodium excretion did not change significantly. On the other hand, pretreatment with dopamine, which caused a similar degree of vasodilation to that caused by verapamil, did not prevent the response to a subsequent meat meal. Thus verapamil specifically prevented the normal increases in renal hemodynamics after protein feeding, suggesting that protein-stimulated renal vasodilation requires intact voltage-dependent calcium channels.

Acetylcholine↗