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Biomedical subjects

C I Thompson

Publications and source records attributed to C I Thompson.

At least 19 recordsLinked to original sources
PubMed1992

Mechanisms of coronary vasodilatation produced by ATP in guinea-pig isolated perfused heart.

1. Isolated hearts of guinea-pigs were perfused in vitro with a physiological salt solution via a retrograde aortic cannulation (Langendorff preparation) at constant perfusion pressure. Bolus intra-arterial injections of various vasodilator drugs were made and the coronary flow responses were measured with an electromagnetic flow probe placed in the arterial inflow circuit. Inhibitory drugs were infused intra-arterially. 2. Nitro-L-arginine (NLA; 500 microM), an NO synthesis inhibitor, decreased coronary baseline flow by 16 +/- 0.8%, converted acetylcholine-induced coronary vasodilatation to vasoconstriction and had no effect on coronary flow responses to adenosine or papaverine. Sodium nitroprusside-induced responses were enhanced during NLA infusion by 46 +/- 11%. 3. Adenosine 5'-triphosphate (ATP) increased coronary flow but coronary flow responses to ATP were not altered by infusion of NLA. 4. ATP-induced coronary dilatation was not significantly attenuated by infusion of the adenosine receptor antagonist XAC, (xanthine amine congener; 2 microM), whereas XAC decreased coronary flow responses to adenosine by 75% +/- 5%. 5. ATP-induced coronary flow responses were reduced by only 31 +/- 4% during indomethacin infusion (2.8 microM) whereas indomethacin completely eliminated the initial vasoconstriction phase and greatly attenuated the peak flow and duration of the later vasodilatation phase seen in response to arachidonic acid (0.75 nmol). Indomethacin had no effect on vasodilatations produced by adenosine or prostaglandin I2. 6. These results indicate that ATP-induced coronary dilatation in the isolated, perfused heart of the guinea-pig is not dependent upon NO production or upon degradation of ATP to adenosine. The coronary dilator action of ATP may be partially dependent (approximately 30%) upon the production of vasodilator prostaglandins.

Adenosine Triphosphate↗
PubMed1992

Vasodilative and anti-adrenergic effects of adenosine in diabetic rat hearts.

To determine the vasodilative and negative inotropic effects of adenosine in hearts of diabetic rats, isolated hearts, perfused at constant perfusion pressure (Langendorff technique), were prepared from age-matched control Wistar rats and rats made diabetic 10 weeks prior to study by a single injection of streptozotocin (65 mg.kg-1, i.p.). Adenosine and nitroprusside each increased coronary inflow when administered either as bolus injections or as infusions. Coronary flow responses to nitroprusside were unchanged in diabetic hearts. Coronary flow responses of diabetic hearts to adenosine injections were unchanged, but responses to adenosine infusions tended to be larger than in normal hearts. Diabetes had no significant effect on the EC50 for either vasodilator. Adenosine inhibited the inotropic effect of isoproterenol (enhanced left ventricular (LV) pressure (P) and LV dP/dtmax) in normal hearts, independently of its vasodilative action. This negative inotropic action of adenosine appeared equally strong in diabetic hearts. We conclude that adenosine's coronary vasodilative and anti-beta-adrenergic, negative inotropic effects in the rat heart were not diminished after 10 weeks of streptozotocin-induced diabetes mellitus. Thus, earlier reports of diminished adenosine dilative efficacy in experimental diabetes may have been unique to those particular models.

Adenosine↗
PubMed1992

Renal hemodynamic effects of exogenously administered adenosine and polyadenylic acid.

Steady-state intrarenal arterial infusion of adenosine (Ado) suggests that there may be both afferent and efferent arteriolar actions of Ado. This study attempts to further differentiate vascular sites of action of Ado during an intrarenal infusion of Ado. We measured the filtration fraction (FF) during intrarenal infusion of Ado (33.3 nmol.kg-1 x min-1) in anesthetized dogs to determine its transient actions on renal hemodynamics. FF remained unchanged from preinfusion levels (0.42 +/- 0.01 vs. 0.46 +/- 0.01, respectively) at a time when renal blood flow (RBF) was significantly decreased (52 +/- 6% of control). During steady state, RBF was 96 +/- 5% of control, while FF was significantly decreased from control (0.27 +/- 0.02). To determine whether vasoconstriction and dilation to Ado are mediated by receptors accessible from intra- or extravascular compartments, two Ado analogues [oligoadenylic acid (oligo[A]), mol wt 5,000, and polyadenylic acid (poly[A]), mol wt > 100,000] were injected into the renal artery, and RBF response was compared with that of Ado. Poly[A] produced a transient vasodilation (42 +/- 6% increase in RBF), whereas oligo[A] produced a transient vasoconstriction (25 +/- 5% decrease in RBF). Responses to steady-state infusion of poly[A] (10 nmol.kg-1 x min-1) were determined in 11 anesthetized sodium-depleted dogs. Poly[A] produced a sustained significant increase in RBF from 2.83 +/- 0.31 to 3.92 +/- 0.40 ml.g-1 x min-1. This decrease in renal vascular resistance was blocked by an intrarenal infusion of the Ado antagonist theophylline (0.5 mumol.kg-1 x min-1, 2.68 +/- 0.38 vs. 2.85 +/- 0.38 ml.g-1 x min-1).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗
PubMed1992

Bilateral atrial appendectomy abolishes increased plasma atrial natriuretic peptide release and blunts sodium and water excretion during volume loading in conscious dogs.

The atrial appendages contain most of the atrial natriuretic factor (ANF) in the mammalian heart, and atrial appendage mechanical function predicts ANF secretion during volume loading. To demonstrate the crucial role of the atrial appendages in ANF release, we first measured hemodynamics and changes in plasma ANF after injection of 1,000 ml i.v. normal saline in conscious dogs and again after bilateral atrial appendectomy; we next measured changes in renal function using infusions of atriopeptin 24 to achieve plasma levels corresponding to levels achieved during volume loading; and we lastly measured renal function during acute volume expansion and also after atrial appendectomy. Plasma ANF increased from 65 +/- 11 to 246 +/- 54 pg/ml after volume loading but did not increase after atrial appendectomy. Atrial appendectomy did not alter the tachycardia or hemodynamic effects of volume loading. Infusion of 10 ng/kg/min atriopeptin 24 increased plasma ANF from 50 +/- 9 to 234 +/- 54 pg/ml, increased urine output 34 +/- 10%, and increased sodium excretion 62 +/- 10% in dogs with intact atrial appendages. Renal function was compared in dogs before atrial appendectomy: 20, 40, and 60 minutes after volume loading, urine flow rate increased by 5.9 +/- 0.5, 6.9 +/- 0.4, and 4.4 +/- 0.8 ml/min, while sodium excretion increased by 717 +/- 60, 839 +/- 84, and 582 +/- 57 mueq/min. After atrial appendectomy urine flow rate increased 2.1 +/- 0.7, 2.7 +/- 0.7, and 2.0 +/- 0.6 ml/min, and sodium excretion increased only by 327 +/- 110, 324 +/- 77, and 340 +/- 92 mueq/min (p less than 0.01) during volume loading.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Salt appetite in rat pups: ontogeny of angiotensin II-aldosterone synergy.

Preweanling rats were tested to determine whether angiotensin II (ANG II) and aldosterone (Aldo) act synergistically to enhance salt appetite at 12 and 17 days. Twelve-day-old pups received one of four hormone treatments in four doses: 1) ANG II only [1, 2, 10, or 100 ng pulse intracerebroventricular (icv)], 2) Aldo only (1, 2, 10, or 40 micrograms/day sc), 3) Aldo + ANG II (four individual doses combined), or 4) vehicle. Seventeen-day-old rats received the same treatments in two doses (2 or 100 ng ANG II; 2 or 40 micrograms Aldo). Pups were presatiated with milk through anterior oral catheters and then given either 4% NaCl or water for 30 min. Intake was assessed by body weight change. At both ages, ANG II enhanced salt (and water) intake, and Aldo enhanced salt (but not water) intake. Minimum effective doses were comparable to those reported for adults. ANG II-Aldo synergy was absent at 12 days and present at 17 days, when salt intake was 590% greater than the summed intakes evoked by ANG II and Aldo alone. The neural mechanisms for ANG II-Aldo synergy thus mature later than those mediating the hormone's individual actions in arousing salt appetite.

Aldosterone↗
PubMed1989

Dual 24-hour feeding response to 2DG in rats: daytime increase and nighttime decrease.

Thirty-six rats were injected IP with 2DG (0, 250, or 500 mg/kg) at 7-day intervals, once at light onset (7 a.m.) and once at dark onset (7 p.m.), and postinjection food intake was monitored for 24 hours. Five hundred mg/kg 2DG caused food intake to rise above control levels during the first 6 hours of daylight, regardless of whether the injection had occurred that morning or the previous evening, whereas intake during the first 6 hours of darkness was consistently below control levels. In a second study, 24 rats were injected first at 7 a.m. (500 mg/kg 2DG or saline), and 7 days later at 7 p.m. (opposite drug), and food was withheld 12 hours until the light:dark period had changed. For 12 hours after food was returned, 2DG again decreased nighttime food intake (Injection 1) and increased daytime intake (Injection 2). 2DG's dual long-term effects cannot be accounted for either by malaise or by an initial action that later is compensated by its opposite. Rather, 2DG (500 mg/kg) appears to exert two independent, opposite alimentary effects which persist 18-24 hours and which change direction with phase changes in the light:dark cycle.

Animals↗
PubMed1989

Chlamydia trachomatis infections in the female rectums.

One hundred and fifteen consecutive new women patients were examined in a department of genitourinary medicine for evidence of infection with Chlamydia trachomatis in the rectum, in addition to the routine screening tests performed. An impression smear of the rectal mucosa was made as a semiquantitative assessment of the degree of proctitis, and details of bowel habit and symptoms and of sexual practice were noted. Chlamydial infection was found in the cervices of 15 (13%) and the rectums of six (5%). Rectal infection was significantly associated with rectal bleeding and microscopic evidence of proctitis, but not with diarrhoea or macroscopic proctitis.

Adolescent↗
PubMed1986

Elevation of intrarenal adenosine by maleic acid decreases GFR and renin release.

Maleic acid administration produces a defect in tubular reabsorption resembling that seen in the Fanconi syndrome and also causes a decrease in glomerular filtration rate (GFR). The mechanism by which maleic acid alters renal function is uncertain, though the tubular defect is known to be associated with decreased ATP levels. Because of this alteration in nucleotide metabolism the present study was undertaken to determine the role of elevated endogenous adenosine in mediating the maleic acid-induced changes in renal function. Since the renal effects of exogenous adenosine are enhanced by sodium-depletion and attenuated by sodium-loading, the present study compared the time course of the effects of maleic acid on renal function in 10 dogs maintained on a low sodium diet, and 10 dogs maintained on a high sodium diet. In addition, we examined the effect of maleic acid on adenosine levels in renal venous plasma, on the urinary excretion of adenosine, and the effect of the adenosine antagonist, theophylline, on the maleic acid-induced changes in renal function. After 100 min of maleic acid, GFR was decreased significantly by 55 +/- 4% of control in the sodium-depleted dogs, and by 39 +/- 4% of control in the sodium-loaded dogs. In the sodium-depleted dogs, renin release was also significantly depressed (12 +/- 8% of control) during the infusion of maleic acid. The fractional excretion of sodium was significantly increased in both groups. The renal venous concentration of adenosine and the urinary excretion of adenosine were both significantly increased during maleic acid.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗
PubMed1985

Renal handling and production of plasma and urinary adenosine.

The present study was undertaken to determine the renal handling of plasma adenosine and the relative contribution of the kidney to the adenosine in the renal venous plasma and urine. Injections of radiolabeled adenosine, as a tracer of arterial adenosine, along with reference compounds (either inulin or 9-beta-D-arabinofuranosyl hypoxanthine, an analogue of adenosine that does not occupy the nucleoside carrier) were coupled with measurements of endogenous adenosine in the arterial and renal venous plasma and urine of 11 anesthetized dogs. The arterial and venous concentration of endogenous adenosine was 60 +/- 16 and 52 +/- 10 nM, respectively. Urinary adenosine concentration was 312 +/- 53 nM and the fractional excretion was 0.71 +/- 0.14. Of the radiolabeled adenosine injected into the renal artery, approximately 53 +/- 3% of the filtered tracer was recovered in the urine, and only 11 +/- 1% of the tracer was recovered in the venous plasma. These results demonstrate uptake of adenosine from both the tubular and vascular compartments, and analysis of single-injection multiple-indicator curves indicates that a substantial amount of the extracted arterial adenosine enters and remains in cells. We conclude that arterial plasma contributes significantly to adenosine excreted in the urine but only minimally to renal venous adenosine. Furthermore, any intervention that alters cellular uptake and metabolism of adenosine may lead to significant changes in extracellular adenosine.

Adenosine↗
PubMed1985

Dipyridamole decreases glomerular filtration in the sodium-depleted dog. Evidence for mediation by intrarenal adenosine.

To determine the renal effects of inhibiting the uptake and subsequent metabolism of endogenous adenosine, dipyridamole, a nucleoside transport inhibitor, was infused intrarenally into anesthetized dogs. Dipyridamole (24 micrograms/kg per min) inhibited the cellular extraction of [14C]adenosine (72 +/- 3% vs. 9 +/- 3%) and elevated the excretion of endogenous adenosine (0.60 +/- 0.08 to 1.70 +/- 0.21 nmol/min, P less than 0.05). The action of exogenous adenosine to decrease glomerular filtration rate is known to be enhanced by sodium depletion, and is minimal or absent in sodium-loaded animals. To ascertain whether dietary sodium intake alters the renal effects of elevated endogenous adenosine, dipyridamole was infused into sodium-depleted and sodium-loaded dogs. In the sodium-depleted dogs (n = 9), dipyridamole infusion decreased the glomerular filtration rate by 59 +/- 7% (20 +/- 1 to 8 +/- 2 ml/min, P less than 0.05) which returned to control levels within 30 minutes after stopping infusion of dipyridamole. Renal vascular resistance was unchanged during dipyridamole infusion. In the sodium-loaded dogs (n = 5), dipyridamole had no effect on glomerular filtration rate (22 +/- 4 vs. 25 +/- 3 ml/min) or renal vascular resistance. In a separate series of sodium-depleted dogs (n = 8), the dipyridamole-induced decrease in glomerular filtration rate was completely reversed or inhibited by theophylline, an adenosine receptor antagonist. These experiments demonstrate that inhibition of cellular uptake of adenosine elevates adenosine levels, that dipyridamole decreases glomerular filtration rate in sodium-depleted but not sodium-loaded dogs, and that the decrease in glomerular filtration rate is inhibited by theophylline. We conclude that the decrease in glomerular filtration rate during dipyridamole administration is mediated by increased endogenous adenosine.

Adenosine↗
PubMed1984

Food intake during tumor growth: anorexia in genetically obese ob/ob mice and hyperphagia in lean mice.

Recent findings indicate that obese (ob/ob) mice suffer a low incidence of lung metastasis and survive longer than lean (+/?) littermates following injection with B16 melanoma cells [34]. The present study examined the food intake of obese and lean mice during the growth of this tumor. Mice from both groups increased their food intake by small and approximately equal amounts during the first three quarters of the survival period following injection with 10(6) cells, and body weights remained fairly stable. During the final quarter, however, obese mice became anorexic whereas lean mice became intensely hyperphagic; body weights changed accordingly. Thus, food intake is differentially affected by tumor growth in this form of genetic obesity.

Animals↗
PubMed1984

Adenosine-induced decrease in renin release: dissociation from hemodynamic effects.

Adenosine has been reported to produce a biphasic renal blood flow (RBF) response (vasoconstriction followed by a return of flow to control level) and a decrease in glomerular filtration rate (GFR) when infused into the kidney. Intrarenal adenosine infusion also leads to a decrease in renin release. By altering the hemodynamic response to adenosine, we sought to determine whether the decrease in renin release depends on vascular or filtration-induced events. In nine dogs with nonfiltering kidneys, adenosine infusion (3 X 10(-7) mol/min) resulted in a biphasic RBF response and an inhibition of renin release (309 +/- 53 vs. 71 +/- 26 ng ANG I/min). In 11 dogs treated with verapamil (10 micrograms X kg-1 X min-1) no vasoconstriction or decrease in GFR occurred; however, renin release was inhibited by adenosine (1,300 +/- 159 vs. 534 +/- 225 ng ANG I/min). In a third group of nine dogs whose ureteral pressure was raised to 80 cmH2O, adenosine infusion produced a sustained vasoconstriction and an inhibition of renin release (3,086 +/- 1,144 vs. 328 +/- 130 ng ANG I/min). These experiments, in which the renin release effects of adenosine are dissociated from the hemodynamic effects, lead us to conclude that the inhibition of renin release produced by adenosine does not depend either on the vascular or filtration-induced effects of adenosine.

Adenosine↗
PubMed1983

Genetically obese mice: resistance to metastasis of B16 melanoma and enhanced T-lymphocyte mitogenic responses.

The metastasis of B16 melanoma cells differed significantly in obese (ob/ob) and lean (+/?) female mice of strain C57BL/6J. When the mice were inoculated subcutaneously with melanoma cells at 10 to 11 months of age, the primary tumor grew more slowly in obese than in lean littermates and the frequency of lung metastasis was greatly reduced. When the mice were injected with the cells at 4 to 7 months, the primary tumor grew at the same rate in obese and lean mice, but the obese mice again showed a significantly reduced frequency of lung metastasis. That this effect was related to an enhanced immunocompetence in obese mice was supported by the finding that splenic lymphocytes of ob/ob mice showed three times the proliferative response to the T-cell mitogen concanavalin A compared with the proliferative response of lean control mice. The ob/ob mouse may provide a model for the study of enhanced immunocompetence in obese individuals.

Animals↗
PubMed1983

Enhanced tumor resistance and immunocompetence in obese (ob/ob) mice.

Genetically obese mice (C57BL6/J-ob/ob) have enhanced resistance to metastasis of the B16 melanoma in comparison with lean littermate controls. Here we show that this difference is not due to differences in the health status of these mice. We show also that the obese mice have enhanced immunocompetence as indicated by enhanced proliferative responses of their splenic lymphocytes to T-cell mitogens but not to a B-cell mitogen. The obese mice also produced twice as many antibody-secreting cells in their spleens in response to immunization in vivo with sheep erythrocytes as did lean mice. There were no differences between the two genotypes in cytolytic T lymphocyte activity after immunization in vivo with allogeneic cells. An opioid theory of enhanced immunocompetence could account for our results.

Animals↗
PubMed1983

Phasic release of adenosine during steady state metabolic stimulation in the isolated guinea pig heart.

If adenosine is the major factor responsible for myocardial metabolic vasodilation, its release should be sustained as long as oxygen consumption and coronary flow are augmented. To see if adenosine meets this criterion, we examined the time course of its release during norepinephrine infusion in isolated, non-working guinea pig hearts (n = 8). During an 11-minute infusion period (steady state perfusate concentration = 6 X 10(-8) M), the coronary effluent was collected over 30-second intervals for measurements of coronary flow (ml/min per g), and adenosine and inosine release (pmol/min per g). Myocardial oxygen consumption (MVO2 = microliter O2/min per g) was measured at 1, 4, 6.5, and 11 minutes. Control values of coronary flow, myocardial oxygen consumption, and adenosine and inosine release were 7.5 +/- 0.4, 85 +/- 5, 22 +/- 5, and 431 +/- 39, respectively. During norepinephrine infusion, coronary flow, myocardial oxygen consumption, and adenosine release attained maximal levels within one minute (inosine within 2 minutes). These values were 10.6 +/- 0.4, 125 +/- 9, 849 +/- 110, and 2595 +/- 581, respectively. Thereafter, coronary flow and myocardial oxygen consumption values were sustained. In contrast, adenosine and inosine release significantly declined to nadirs by 9.5 minutes. Thereafter, steady state levels were maintained at 117 +/- 24 and 960 +/- 294, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗
PubMed1979

Hypophagia follows the initial hyperphagia produced by 2-deoxy-D-glucose in rats.

The glucose analogue 2-deoxy-D-glucose (2DG) inhibits glucose metabolism and causes a rapid increase in food consumption in most species. This increase is most apparent during the first 6 postinjection hours, although it may persist as long as 10 hr. There are no published descriptions of alterations in food consumption subsequent to the hyperphagia. In the present study male and female rats were injected with 2DG (750 mg/kg IP), insulin (regular, 20 U/kg SC) or distilled water, and food intake was compared to baseline levels during the next 1, 6 and 24 hr. Results showed that food intake: (1) was not affected by injections of water: (2) was higher than normal during all 3 time periods following insulin injections: and (3) was higher than normal at 1 and 6 hr following 2DG, but significantly lower than normal by the end of 24 hr. The reasons underlying the development of hypophagia subsequent to the initial hyperphagia produced by 2DG are presently unknown.

Animals↗
PubMed1979

Learning ability in adult female rats perinatally exposed to methadone.

Cognitive functioning of adult female rats that were maternally exposed to methadone (5 mg/kg daily) during gestation and/or lactation was studied by assessing performance on a food-motivated light-dark discrimination learning test and on active and passive shock-avoidance tests. Methadone-exposed rats exhibited difficulties on the light-dark discrimination learning and the active avoidance tests, and behavioral deficits appeared to be related to the timing and duration of drug treatment. On the light-dark discrimination test only 33% of the rats in the gestation group and 25% of the animals in the lactation group met criterion in comparison to 87% of the control rats. Thirty-three percent of the animals in either the gestation or gestation-lactation groups met criterion on the active avoidance test in contrast to 87% of the controls. These data suggest that perinatal exposure to methadone impairs cognitive abilities in the adult female rat.

Animals↗