Biomedical subjects

F G Smith

Publications and source records attributed to F G Smith.

At least 19 recordsLinked to original sources

PubMed2001

Renal hemodynamic effects of L-NAME during postnatal maturation in conscious lambs.

The purpose of the present study was to investigate the effects of the L-arginine analogue, NG-nitro-L-arginine methyl ester, L-NAME, in modulating renal hemodynamics during postnatal maturation in conscious chronically instrumented lambs. To this end, renal hemodynamic responses to intravenous injection of 10, 20, and 40 mg/kg L-NAME, as well as its inactive enantiomer D-NAME, were measured for 4 h in conscious lambs approximately 1 week (n=10), 3 weeks (n=12), and 6 weeks (n=14) of age. Administration of L-NAME was associated with an increase in renal vascular resistance (RVR) leading to a decrease in renal blood flow. One-week-old lambs were more sensitive to the effects of L-NAME, a marked increase in RVR occurring after the smallest dose administered at 1 week but not at 3 and 6 weeks of age. Renal hemodynamic effects of L-NAME as well as the duration of the responses were also age dependent, such that changes in RVR were greatest and most prolonged in 1-week-old lambs. In addition, a smaller dose of L-NAME was required to attenuate acetylcholine-induced renal vasodilation in lambs aged 1 week compared with older animals. Our data provide new evidence to support the premise that endogenously produced nitric oxide plays a predominant role in regulating renal vascular tone early in life.

Aging↗

PubMed2001

Prenatal exposure to nicotine impairs protective responses of rat pups to hypoxia in an age-dependent manner.

Experiments were carried out on rat pups to investigate the interaction between prenatal exposure to nicotine and postnatal age on protective responses that promote survival during exposure to hypoxia. From days 6 or 7 of gestation, pregnant rats received either nicotine (approximately 6 mg of nicotine tartrate/kg of body weight per day) or vehicle continuously via a 28-day osmotic minipump. On postnatal days 1--2, 5--6 and 10--11, the pups were exposed either to a single period of hypoxia produced by breathing an anoxic gas mixture (97% N(2) and 3% CO(2)) and their time to last gasp determined, or they were exposed repeatedly to hypoxia and their ability to autoresuscitate from primary apnea determined. Prenatal exposure to nicotine decreased the time to last gasp, but only in the 1--2-day-old animals. The total number of gasps was, however, increased in this age group due to the effect of nicotine on the gasping pattern. Furthermore, prenatal exposure to nicotine decreased the number of successful autoresuscitations and influenced the cardiorespiratory events preceding death in the 1--2- and 5--6-day-old pups but not in the 10--11-day-old pups. Thus, our experiments show that prenatal exposure to nicotine impairs protective responses of rat pups that may sustain life during exposure to hypoxia in an age-dependent manner.

Age Factors↗

PubMed2001

Development and evaluation of a Research Project Program for medical students at the University of Calgary Faculty of Medicine.

This essay outlines the development and evaluation of the Research Project Program (RPP) ten years after its introduction into the medical curriculum at the University of Calgary. The RPP consists of two mandatory for-credit courses. Students have the option of conducting either two smaller independent research projects or one larger project over the two years. At the end of the second-year course the students complete an evaluation of the RPP in which they are asked to assess and comment upon various aspects of the program. The authors compared data available from years one (the class of 1990) and ten (the class of 2000) and found significant differences between the two classes' approaches to the RPP. Most of the class of 2000 (89%) carried out two-year independent in-depth research projects spanning a wide range of topics. Half of these projects involved individual collection and analyses of data using experimental methods; this represented a 2.25-fold increase over the first year of the program. In the class of 2000, 44% of students presented their results at a newly implemented research symposium; an additional 22% of students presented their results at local, national, or international meetings. Further, 59% of the class of 2000 had either submitted or were planning to submit their research for peer-reviewed publication. In contrast, none of the students of the class of 1990 formally presented their research, and only 11% planned to submit their research findings for publication. The RPP has evolved in the ten years since its implementation, but the authors believe the program continues to foster independent learning and analytic and problem-solving skills.

Alberta↗

PubMed2001

Nitric oxide modulates arterial baroreflex control of heart rate in conscious lambs in an age-dependent manner.

Experiments were carried out in conscious chronically instrumented lambs aged 1 (n = 6) and 6 wk (n = 5) to evaluate the arterial baroreflex control of heart rate (HR) during postnatal maturation and to investigate any modulatory role of endogenously produced nitric oxide (NO). Before and after intravenous administration of 20 mg/kg of the L-arginine analog N(G)-nitro-L-arginine methyl ester (L-NAME), the arterial baroreflex was assessed by measuring HR responses to increases and decreases in systolic arterial pressure achieved by intravenous administration of phenylephrine and sodium nitroprusside. The HR range over which the baroreflex operates and minimum HR as well as maximum gain were greater at 1 than at 6 wk of age. These age differences were abolished in the presence of L-NAME, which decreased the HR range and gain of the arterial baroreflex control of HR at 1 but not at 6 wk of age. These data provide new information that age-dependent effects of the arterial baroreflex appear to result from effects of endogenously produced NO.

Age Factors↗

PubMed2001

Age-dependent renal responses to the bradykinin B(2)- receptor antagonist icatibant in conscious lambs.

To investigate the role of endogenously produced bradykinin in modulating renal function during postnatal maturation, various parameters of glomerular and tubular function were measured for 1 h before and after intravenous injection of 12.5 microg/kg of the specific B(2)-receptor antagonist icatibant to conscious, chronically instrumented lambs aged approximately 1 (n = 7) and approximately 6 wk (n = 7). In response to icatibant, and in the absence of any changes in renal hemodynamics, there was an approximately 80% decrease in glomerular filtration rate (GFR) at 20 min in 1-wk-old lambs that was sustained for 60 min; in 6-wk-old lambs, there was an approximately 70% decrease in GFR by 20 min, with control levels being reached by 40 min. Icatibant administration was also associated with significant decreases in urinary flow, Cl(-), and K(+) excretion rates that were similar in both groups of lambs, whereas Na(+) excretion decreased only in 6-wk-old lambs. We conclude that bradykinin modulates glomerular and tubular function in an age-dependent manner.

Aging↗

PubMed2001

Threshold levels of maternal nicotine impairing protective responses of newborn rats to intermittent hypoxia.

Experiments were carried out to determine the threshold level of maternal nicotine that impairs protective responses of rat pups to hypoxia. From days 6 or 7 of gestation, pregnant rats received either vehicle or nicotine (1.50, 3.00, or 6.00 mg of nicotine tartrate. kg body wt(-1).day(-1)) or vehicle continuously via a subcutaneous osmotic minipump. On postnatal days 5 or 6, pups were exposed to a single period of hypoxia produced by breathing an anoxic gas mixture (97% N(2) or 3% CO(2)) and their time to last gasp was determined, or they were exposed to intermittent hypoxia and their ability to autoresuscitate from hypoxic-induced primary apnea was determined. Perinatal exposure to nicotine did not alter the time to last gasp or the total number of gasps when the pups were exposed to a single period of hypoxia. The number of successful autoresuscitations on repeated exposure to hypoxia was, however, decreased in pups whose dams had received either 3.00 or 6.00 mg of nicotine tartrate/kg body wt; these dosage regimens produced maternal serum nicotine concentrations of 19 +/- 6 and 35 +/- 8 ng/ml, respectively. Thus our experiments define the threshold level of maternal nicotine that significantly impairs protective responses of 5- to 6-day-old rat pups to intermittent hypoxia such as may occur in human infants during episodes of prolonged sleep apnea or positional asphyxia.

Analysis of Variance↗

PubMed2000

Chronic furosemide treatment alters renal responses to furosemide in conscious lambs.

Despite the widespread chronic use of furosemide in the clinical management of a variety of fluid and electrolyte disorders in human infants, the physiological responses to furosemide in the newborn after chronic furosemide treatment are not known. The present experiments were conducted to determine the effects of chronic furosemide treatment on renal responses to acute furosemide challenge in conscious, chronically instrumented lambs. Experiments were carried out on day 1 (before chronic treatment) and on day 7 (after chronic treatment) in lambs given intravenous injections of either furosemide (1 mg/kg per 12 h for 5 days, n=9) or vehicle (0 mg/kg per 12 h for 5 days, n=4). Furosemide-treated animals responded to acute furosemide challenge on day 7 with attenuation of natriuresis and diuresis, and augmentation of kaliuresis compared with responses on day 1. Baseline renin production was elevated, although the renin response to furosemide was similar in chronic furosemide-treated and vehicle-treated lambs. Baseline aldosterone levels were not altered by chronic furosemide treatment, but the aldosterone response to acute furosemide injection was decreased after chronic furosemide treatment. Therefore, chronic furosemide treatment alters renal responses to furosemide in conscious lambs, and alters the aldosterone response to acute furosemide challenge.

Aldosterone↗

PubMed2000

Renin and heart rate responses to haemorrhage are age dependent in conscious lambs.

The present experiments were carried out in conscious lambs (1-2 weeks old, n = 9) and older sheep (11-12 weeks old, n = 11) to determine whether the cardiovascular and endocrine responses to 0, 10 and 20 % haemorrhage were developmentally regulated. The major novel finding of our study is that throughout the first 3 months of postnatal life, there is a similar decrease in mean arterial pressure and a similar restoration of pressure to pre-haemorrhage levels, for the same degree of blood loss, yet the mechanisms used to restore pressure appear to be age dependent as follows. In lambs, but not in older sheep, heart rate increased for 1 h after 20% haemorrhage. Activation of the renin-angiotensin system was also greater and more prolonged in lambs than in older sheep following haemorrhage, and occurred at a lesser degree of blood loss. Plasma arginine vasopressin responses to haemorrhage were, however, similar in both age groups. These data provide new information that some of the mechanisms used to restore arterial pressure following blood volume depletion appear to be age dependent.

Aging↗

PubMed2000

Postnatal age influences the ability of rats to autoresuscitate from hypoxic-induced apnea.

Failure to autoresuscitate from apnea by gasping has been suggested to have a role in sudden infant death. Little is known, however, about the factors that influence the ability of gasping to sustain life during acute hypoxia in the newborn. The present experiments were carried out on 105 rat pups to investigate the influence of postnatal age on the time to last gasp during a single hypoxic exposure and on the ability to autoresuscitate from primary apnea during repeated hypoxic exposures. On days 1-2, 5-6, 10-11, 15-16, and 19-20 postpartum, each pup was placed into a temperature-controlled chamber regulated to 37 +/- 1 degrees C and was exposed either to a single period of hypoxia produced by breathing an anoxic gas mixture (97% N(2)-3% CO(2)), and the time to last gasp was determined, or repeated exposure to hypoxia was performed, and the ability to autoresuscitate from primary apnea was determined. Increases in postnatal age decreased the time to last gasp following a single hypoxic exposure and decreased the number of successful autoresuscitations following repeated hypoxic exposures. Thus our data provide evidence that postnatal age influences protective responses that may prevent death during hypoxia as may occur during episodes of prolonged sleep apnea.

Age Factors↗

PubMed2000

Renal haemodynamic effects of B2 receptor agonist bradykinin and B2 receptor antagonist HOE 140 in conscious lambs.

The present study was designed to test the hypothesis that the high renal vascular resistance characteristic of the newborn results from age-dependent changes in the responsiveness of the renal vasculature to kinins. Two studies were carried out in conscious, chronically instrumented lambs aged 1 and 6 weeks. Firstly, we measured the renal blood flow response to intra-arterial injection of the B2 receptor agonist bradykinin over the range of doses 0-800 ng x kg(-1). The ED50 renal blood flow response to bradykinin was 50 ng x kg(-1) in both age groups of lambs. Secondly, we measured the effects of intravenous administration of 12.5 microg x kg(-1) of the specific B2 receptor antagonist HOE 140; this dose attenuated the renal blood flow response to 50 ng x kg(-1) of bradykinin in both age groups. HOE 140 administration was associated with an age-dependent increase in mean arterial pressure, with little effect on heart rate or renal vascular resistance. This study provides new information regarding the effects of kinins in modulating renal haemodynamics during postnatal maturation. We reject our hypothesis and conclude that the high renal vascular resistance of the newborn does not appear to result from age-dependent changes in the responsiveness of the renal vasculature to endogenous kinins.

Aging↗

PubMed1999

Dose-dependent effects of nitric oxide synthase inhibition on systemic and renal hemodynamics in conscious lambs.

The present experiments were carried out to determine the role of nitric oxide in influencing systemic and renal hemodynamics in conscious young sheep. Parameters of cardiovascular function were measured before and for 4 h after intravenous injection of either L-NAME (NG-nitro-L-arginine methyl ester) or D-NAME (N(G)-nitro-D-arginine methyl ester) at doses of 10, 20, or 40 mg/kg in 13 conscious, chronically instrumented young sheep aged 43 +/-5 days. Blood pressure increased and heart rate decreased in a dose-dependent manner following administration of L-NAME. Renal vascular resistance was increased for 10 min following a dose of 10 mg/kg of L-NAME and for 120 min following a dose of 40 mg/kg of L-NAME. The renal vasodilatory response to close arterial injection of 1 microg/kg of acetylcholine was attenuated by L-NAME in a dose-dependent manner. These experiments provide the first information that under normal physiological conditions in conscious young animals, nitric oxide influences systemic and renal hemodynamics.

Acetylcholine↗

PubMed1999

Acetylcholine chloride and renal hemodynamics during postnatal maturation in conscious lambs.

To test the hypothesis that acetylcholine-induced relaxation of the renal artery decreases with postnatal age, we measured parameters of renal hemodynamics before and for 35 s after aortic suprarenal injection of acetylcholine in conscious, chronically instrumented lambs aged approximately 1 wk (n = 5) and approximately 6 wk (n = 5). Acetylcholine was administered in one of five doses ranging from 0 to 10 mg/kg body wt; doses were administered randomly, in the same volume. There were significant age- and dose-dependent changes in renal vascular resistance after acetylcholine administration, such that the response was greater in 1-wk-old lambs. After the highest dose tested, renal vascular resistance decreased by 13.6 +/- 7.3 (SD) mmHg. ml(-1). min. g kidney wt in 1-wk-old lambs and by 9.1 +/- 3.2 mmHg. ml(-1). min. g kidney wt in 6-wk-old lambs at 35 s. We also observed a transient renal vasoconstriction before the renal vasodilatation in 6-wk-old lambs but not in 1-wk-old animals. These data provide the first age- and dose-dependent effects of exogenous administration of acetylcholine on renal hemodynamics during maturation in conscious animals.

Acetylcholine↗

PubMed1998

Renal denervation alters cardiovascular and endocrine responses to hemorrhage in conscious newborn lambs.

To investigate the role of renal sympathetic nerves in modulating cardiovascular and endocrine responses to hemorrhage early in life, we carried out three experiments in conscious, chronically instrumented lambs with intact renal nerves (intact; n = 8) and with bilateral renal denervation (denervated; n = 5). Measurements were made 1 h before and 1 h after 0, 10, and 20% hemorrhage. Blood pressure decreased transiently after 20% hemorrhage in intact lambs and returned to control levels. In denervated lambs, however, blood pressure remained decreased after 60 min. After 20% hemorrhage, heart rate increased from 170 +/- 16 to 207 +/- 18 beats/min in intact lambs but not in denervated lambs, in which basal heart rates were already elevated to 202 +/- 21 beats/min. Despite an elevated plasma renin activity (PRA) measured in denervated (12.0 +/- 6.4 ng ANG I . ml-1 . h-1) compared with intact lambs (4.0 +/- 1.1 ng ANG I . ml-1 . h-1), the increase in PRA in response to 20% hemorrhage was similar in both groups. Plasma levels of arginine vasopressin increased from 11 +/- 8 to 197 +/- 246 pg/ml after 20% hemorrhage in intact lambs but remained unaltered in denervated lambs from baseline levels of 15 +/- 10 pg/ml. These observations provide evidence that in the newborn, renal sympathetic nerves modulate cardiovascular and endocrine responses to hemorrhage.

Angiotensin I↗

PubMed1998

Perinatal nicotine exposure impairs ability of newborn rats to autoresuscitate from apnea during hypoxia.

Failure to autoresuscitate by hypoxic gasping during prolonged sleep apnea has been suggested to play a role in sudden infant death. Furthermore, maternal smoking has been repeatedly shown to be a risk factor for sudden infant death. The present experiments were carried out on newborn rat pups to investigate the influence of perinatal exposure to nicotine (the primary pharmacological and addictive agent in tobacco) on their time to last gasp during a single hypoxic exposure and on their ability to autoresuscitate during repeated exposure to hypoxia. Pregnant rats received either nicotine (6 mg. kg-1. 24 h-1) or vehicle continuously from day 6 of gestation to days 5 or 6 postpartum via an osmotic minipump. On days 5 or 6 postpartum, pups were exposed either to a single period of hypoxia (97% N2-3% CO2) and their time to last gasp was determined, or they were exposed repeatedly to hypoxia and their ability to autoresuscitate from primary apnea was determined. Perinatal exposure to nicotine did not alter the time to last gasp, but it did impair the ability of pups to autoresuscitate from primary apnea. After vehicle, the pups were able to autoresuscitate from 18 +/- 1 (SD) periods of hypoxia, whereas, after nicotine, the pups were able to autoresuscitate from only 12 +/- 2 periods (P < 0.001) of hypoxia. Thus our data provide evidence that perinatal exposure to nicotine impairs the ability of newborn rats to autoresuscitate from primary apnea during repeated exposure to hypoxia, such as may occur during episodes of prolonged sleep apnea.

Animals↗

PubMed1997

Systemic and renal hemodynamic effects of hemorrhage in conscious lambs.

The purpose of the present study was to investigate the systemic and renal hemodynamic effects of hemorrhage in the newborn to determine whether the newborn is capable of restoring blood pressure in the face of blood loss at hemorrhage of up to 20% of vascular volume. Experiments were carried out in conscious, chronically instrumented lambs and consisted of measurements before, during, and after hemorrhage at 0 (n = 9), 10 (n = 8), 15 (n = 8), and 20% (n = 8) of blood volume. Right atrial pressure decreased but only after 20% hemorrhage. There was a transient decrease in blood pressure at 10-15% hemorrhage and a sustained decrease in blood pressure after 20% hemorrhage (from 82 +/- 7 to 66 +/- 9 mmHg). Heart rate increased transiently after 15% hemorrhage (from 173 +/- 32 to 204 +/- 66 beats/min); heart rate remained increased for 60 min after 20% hemorrhage from 171 +/- 17 to 214 +/- 31 beats/min. There were no changes in renal vascular resistance in response to hemorrhage of up to 20% of vascular volume. These observations provide evidence that the newborn is capable of buffering blood pressure in response to blood loss of up to 20% of vascular volume and that the renal bed does not appear to contribute to the restoration of blood pressure after blood loss early in life.

Animals↗

PubMed1997

Endocrine effects of pregnancy and exposure to a simulated open field in rats.

In adult rats, exposure to a novel environment, such as a simulated open field, elicits an increase in body core temperature. We have recently shown that this response is attenuated in midpregnancy and abolished at term of pregnancy in rats. We postulated that this gestation-dependent response resulted from alterations in the hypothalamic-pituitary-adrenal axis. To test this hypothesis, we measured the effects of pregnancy on renin, corticosterone, and arginine vasopressin (AVP) responses to exposure to either a simulated open field (30 or 120 min) or to the home cage (30 or 120 min) in rats. Pregnancy increased renin and corticosterone levels but not plasma AVP levels. Exposure to an open field decreased renin and increased plasma AVP levels in nonpregnant rats and on days 15 and 20 of gestation in pregnant rats, compared with home cage responses. Serum corticosterone levels were elevated after exposure to an open field in nonpregnant and pregnant rats, compared with home cage rats, the effect being more prolonged on day 20 of gestation. These observations provide new information on endocrine changes during pregnancy in rats and may help to explain the attenuated stress-induced hyperthermic response to exposure to a novel environment seen near term of pregnancy.

Animals↗

PubMed1997

Effects of renal denervation on cardiovascular and renal responses to ACE inhibition in conscious lambs.

Effects of renal denervation on cardiovascular and renal responses to ACE inhibition in conscious lambs. J. Appl. Physiol. 83(2): 414-419, 1997.-Cardiovascular and renal effects of either the angiotensin-converting enzyme inhibitor captopril or vehicle were measured in chronically instrumented lambs in the presence (intact; n = 6) and absence of renal sympathetic nerves (denervated; n = 5) to determine whether there was an interaction between the renin-angiotensin system and renal sympathetic nerves early in life. Captopril caused a similar decrease in mean arterial pressure (P < 0. 001) in intact and denervated lambs, predominantly through a decrease in diastolic pressure. Heart rate was increased from 177 +/- 34 to 213 +/- 22 (SD) beats/min during captopril compared with vehicle infusion in intact lambs. In denervated lambs, basal heart rates were elevated to 218 +/- 33 beats/min; there was no further increase in heart rate during captopril compared with vehicle infusion. Captopril infusion caused a decrease in renal vascular resistance but only in the absence of renal nerves. These findings provide evidence to suggest that early in life there is an interaction between renal sympathetic nerves and the renin-angiotensin system in regulating renal hemodynamics and the baroreflex control of the heart.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1997

Effects of the angiotensin converting enzyme (ACE) inhibitor, captopril, on the cardiovascular, endocrine, and renal responses to furosemide in conscious lambs.

To test the hypothesis that angiotensin II modulates the physiological responses to furosemide in the newborn, various parameters of cardiovascular, renal, and endocrine function were measured before and after iv injection of furosemide to eight conscious, chronically instrumented lambs in the presence and absence of the angiotensin converting enzyme (ACE) inhibitor, captopril. During ACE inhibition, the rise in heart rate and decrease in renal blood flow in response to furosemide did not occur, and the natriuretic and diuretic responses to furosemide were attenuated by approximately two-thirds. There was also an increase in the urinary excretion of prostaglandin F2 and prostaglandin F1 alpha as well as an increase in the excretion of prostaglandin E2 after furosemide, in the presence of ACE inhibition. Therefore, the cardiovascular, renal, and endocrine responses to furosemide in conscious lambs were significantly altered by ACE inhibition.

6-Ketoprostaglandin F1 alpha↗