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C S Thompson

Publications and source records attributed to C S Thompson.

At least 91 records · Page 5Linked to original sources
PubMed1994

Adenylate and guanylate cyclase activity in the penis and aorta of the diabetic rat: an in vitro study.

OBJECTIVE: To investigate the role of adenylate and guanylate cyclases in the mediation of erection in diabetic rats. MATERIALS AND METHODS: Hyperglycaemic diabetes mellitus was induced in 35 rats using streptozotocin. Two months later the penises and aortae of these rats were excised and cut into rings or segments before being treated with varying concentrations of acetylcholine (Ach), sodium nitroprusside (NaNP), prostaglandin E1 (PGE1) and adrenaline (AD). The levels of adenosine 3'5'-cyclic monophosphate (cAMP) and guanosine 3'5'-cyclic monophosphate (cGMP) so generated were measured by radioimmunoassay and the results compared with those from seven age-matched control rats that had not been given streptozotocin. RESULTS: Ach-stimulated cGMP synthesis was impaired in the aortae in diabetic rats. Ach-stimulated cGMP synthesis was undetectable in the penis. NaNP-stimulated cGMP and PGE1-stimulated cAMP synthesis was enhanced in both the penises and aortae in diabetic rats compared with controls. AD-stimulated cAMP synthesis was enhanced in the aorta in diabetic rats compared with controls, but AD had no effect on cAMP synthesis in the penis. CONCLUSION: Ach-stimulated nitric oxide (NO) synthesis is impaired in the vasculature of diabetic rats and an Ach-NO axis may not be present in the penis of the rat. The enhanced capacity of the penis and vasculature to generate cAMP and cGMP may constitute an adaptive response to counteract the reduction in receptor-linked NO release. Impaired adenylate or guanylate cyclase activity does not contribute to erectile dysfunction in diabetic rats.

Adenylyl Cyclases↗
PubMed1994

Adrenoceptor-linked [45Ca2+] uptake in platelets from diabetic rats: a model for human platelets.

Adrenoceptor-linked 45 calcium uptake was investigated in platelet from diabetic rats (hyperglycaemic, streptozotocin-induced, of 60 days duration). Basal uptake was markedly enhanced in platelets from diabetic rats compared with controls. However, whereas adrenaline-stimulated uptake was unchanged, isoprenaline-stimulated uptake was significantly reduced and noradrenaline-stimulated uptake significantly increased. These latter data indicate that there are differential alterations of adrenoceptor subtypes in diabetes (i.e. an increase in alpha- but decrease in beta-adrenoceptors). These changes in calcium uptake and in adrenoceptor activity may relate to altered platelet function known to occur in experimental diabetes. Furthermore, the similarity of the rat platelet with that of the human (in terms of absolute calcium uptake, responses to agonists and changes in diabetes), renders the rat platelet an appropriate model for studying calcium dynamics and linked adrenoceptors in diabetes.

Animals↗
PubMed1993

Differential changes of adrenoceptor- and muscarinic receptor-linked prostacyclin synthesis by the aorta and urinary bladder of the diabetic rat.

1. The effect of experimental diabetes mellitus (DM; hyperglycaemic, non-ketototic; 2 months duration) in the rat on receptor-linked prostacyclin (PGI2) synthesis (measured as 6-oxo-PGF1 alpha by radioimmunoassay) was studied in the aorta and urinary bladder using adrenaline, angiotensin II (AII) and acetylcholine (ACh). Signal transduction systems were studied via stimulation of PGI2 synthesis with phorbol ester dibutyrate (PDBU; a protein kinase C activator [PKC]), Ca2+ ionophore A23187 (A23187) and thapsigargin (both elevate intracellular Ca2+, activating phospholipase A2 [PLA2]) and arachidonate (AA; substrate for PGI2 synthesis). 2. In response to adrenaline, AII and phorbol ester, aortic PGI2 release was markedly reduced (all > 75%) in diabetic rats compared to controls. EC50s of the dose-response curves for adrenaline, AII and PDBU were also markedly increased in aortae from DM rats compared to controls. Although there was decreased output of PGI2 in response to A23187 by aortae from diabetic rats compared to controls, there was no difference in the EC50s (mean +/- s.e. mean: diabetic, 2.7 +/- 0.2 x 10(-6) M; controls 2 +/- 0.18 x 10(-6) M). There were no differences in PGI2 release (or in the EC50s) in response to thapsigargin or AA between aortae from diabetic and control rats. 3. In the urinary bladder, there was a marked increase in PGI2 output in response to ACh and a marked decrease in EC50s for the ACh-PGI2 dose-response curves in diabetic rats (EC50 = 5.8 +/- 0.32 x 10(-7) M) compared to controls (EC50 = 2.2 +/- 0.15 x 10(-6) M). Although there was an increase in PGI2 output in the urinary bladders from diabetic rats in response to A23187, there were no differences in the EC50s (control, 1.8 +/- 0.2 x 10-6 M; diabetic, 1.1 +/- 0.15 X 10-6 M). In the urinary bladders, there were no differences in PGI2 output (or the EC50s) in response to PDBU, thapsigargin or AA between diabetic or control rats.4. These data indicate that: (i) reduced PGI2 synthesis coupled to adrenoceptors and AII receptors in the aortae of diabetic rats may be due to diminished PKC activity and not to changes in receptor density and/or affinity, Ca2+ stores, PLA2, cyclo-oxygenase or PGI2 synthase; (ii) the diametrically opposite effect of DM on ACh-stimulated PGI2 synthesis is not due to an increase in PKC activity, but possibly to an increase in muscarine receptor number and/or affinity; (iii) changes in receptor-linked PGI2 synthesis are not ubiquitous in experimental DM and may be organ-specific.

Angiotensin II↗
PubMed1992

Epidural anesthesia worsens uterine blood flow and fetal oxygenation during hemorrhage in gravid ewes.

Recent studies suggest that epidural anesthesia initiated before hemorrhage may improve survival and acid-base status in laboratory animals. However, studies of hemorrhagic shock in nonpregnant animals may not be applicable to less severe hemorrhage in pregnant animals. The purpose of this study was to determine whether epidural anesthesia alters maternal and fetal hemodynamic and acid-base responses to hemorrhage in gravid ewes. Twenty-four experiments were performed in twelve chronically instrumented animals between 0.8 and 0.9 of timed gestation. The experimental sequence included: 1) T = 0 min: normal saline 500 ml intravenously; 2) T = 15 min: epidural administration of 0.5% bupivacaine (epidural group) or normal saline (control group); 3) T = 30 min: epidural administration of additional 0.5% bupivacaine (epidural group only) if the sensory level of anesthesia was below T10; 4) T = 45 min: maternal hemorrhage 20 ml/kg over 55 min; and 5) T = 110 min: transfusion of collected maternal blood over 55 min. At 45 min (i.e., 30 min after the epidural injection of bupivacaine), epidural bupivacaine resulted in a median sensory level of T9 in the epidural group. At that time, maternal mean arterial pressure was less (P less than 0.05) in the epidural group than in the control group (14 +/- 2% below baseline versus 4 +/- 1% above baseline, respectively). Maternal mean arterial pressure, heart rate, cardiac output, and uterine blood flow, and fetal PO2 and pH all were significantly less during hemorrhage (P less than 0.05) in the epidural group than in the control group.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, Epidural↗
PubMed1991

Does magnesium sulfate alter the maternal cardiovascular response to vasopressor agents in gravid ewes?

Magnesium sulfate (MgSO4) attenuates the maternal compensatory response to hemorrhage in gravid ewes, perhaps by decreasing the response to endogenous vasopressors. The purpose of this study was to determine whether MgSO4 alters the cardiovascular response of gravid ewes to vasopressor agents. Sixteen gravid ewes underwent a series of experiments consisting of administration of two exogenous and two endogenous vasopressors, each with and without a concurrent MgSO4 infusion. Dose-response curves were constructed for phenylephrine (an alpha 1-adrenergic agonist), ST-91 (an alpha 2-adrenergic agonist), angiotensin II, and arginine vasopressin (AVP). MgSO4 significantly attenuated the increase in maternal mean arterial pressure and systemic vascular resistance and the decrease in cardiac output during ST-91 infusion but not during phenylephrine, angiotensin II, or AVP infusions. MgSO4 significantly attenuated the increase in uterine vascular resistance during phenylephrine, ST-91, and angiotensin II infusions and the decrease in uterine blood flow during phenylephrine and angiotensin II infusions. MgSO4 also appeared to attenuate the decrease in uterine blood flow during ST-91 infusion (P = 0.067). The present study suggests that MgSO4 antagonizes the effects of alpha 1-adrenergic agonists, alpha 2-adrenergic agonists, and angiotensin II on the uterine vasculature, thus providing a level of protection for the fetus in situations of maternal stress.

Angiotensin II↗
PubMed1991

Distribution of 125I-labelled insulin-binding sites in peripheral tissues of the normal and diabetic rat: an autoradiographic study.

In-vitro autoradiography was used to demonstrate the regional distribution of 12I-labelled insulin-binding sites in the liver, kidney and heart of normal rats and rats made diabetic with streptozotocin. The distribution of insulin-binding sites in the liver of control rats was uniformly high, while in the kidney of control rats there was weak 125I-labelled insulin binding in the medulla and dense binding in the cortex. In the hearts of control rats a high density of 125I-labelled insulin-binding sites was evident both in the atrial and ventricular muscle. Non-ketotic diabetes mellitus caused a marked increase in 125I-labelled insulin-binding sites in both the liver and kidney with the former tissue exhibiting a time-dependent (7 to 62 days) increase. There was no apparent effect of diabetes on insulin-binding sites in the heart. Since experimental diabetes causes (1) a decrease in circulating insulin concentration and (2) impaired insulin action at many target tissues, the increase in 125I-labelled insulin-binding sites observed in the present study may represent a compensatory 'up regulation' of insulin receptors.

Animals↗
PubMed1990

The effects of octopamine on juvenile hormone biosynthesis, electrophysiology, and cAMP content of the corpora allata of the cockroach Diploptera punctata.

Juvenile hormone production by the corpora allata of the adult female cockroach, Diploptera punctata, can be modulated by treatment with the biogenic amine, octopamine. Endogenous octopamine has been identified within the CA, using HPLC and electrochemical detection. Treatment with octopamine results in a sinusoidal, dose-dependent inhibition of JH biosynthesis by CA from day 2 virgin females, with maximal inhibition occurring at 10(-10) M and 10(-4 M. In day 4 and day 8 mated female corpora allata octopamine inhibited JH biosynthesis at 5 x 10(-5) M. Although the elevation of either cAMP or cGMP within the CA is known to be associated with an inhibition of JH biosynthesis, treatment with high concentrations of octopamine results in an increase in the level of cAMP but not cGMP. This effect is both dose- and time-dependent. Octopamine treatment also initiates changes in the passive membrane responses of the CA. Superfusion of CA with octopamine results in a pronounced hyperpolarization of CA cells and an increase in the electrotonic potential (indicative of the degree of electrical coupling between CA cells). This effect could be blocked by the octopamine receptor blocker phentolamine. Treatment with octopamine or phentolamine also blocked the hyperpolarization of CA cells normally associated with electrical stimulation of the axon tracts innervating the CA. We hypothesize that octopamine may be a natural neuromodulator of JH production by CA, regulating ion channels in CA cells themselves as well as release of the inhibitory neuropeptide, allatostatin, from the terminals within the CA.

Animals↗
PubMed1990

Magnesium sulfate and promethazine do not interact to cause hypotension in gravid ewes.

The purpose of this study was to determine whether magnesium sulfate and promethazine interact to cause hypotension in gravid ewes. Fifteen experiments were performed in five chronically instrumented animals between 125 and 130 days of timed gestation (term = 145 days). In one group of experiments each animal received magnesium sulfate (4 gm intravenous bolus followed by 4 gm/hr intravenous infusion) then promethazine (50 mg intravenously). In a second group each animal received magnesium sulfate then saline solution as a control. In a third group each animal received saline solution then promethazine. Infusion of magnesium sulfate increased the mean (+/- SEM) serum magnesium concentration to 5.7 +/- 0.6 and 6.6 +/- 0.6 mg/dl in the magnesium sulfate-promethazine and magnesium sulfate-saline solution groups, respectively. Magnesium sulfate slightly decreased maternal mean arterial pressure (p less than 0.05) and increased cardiac output (p less than 0.05) in both the magnesium sulfate-promethazine and magnesium sulfate-saline solution groups. Otherwise there were no significant changes in maternal mean arterial pressure or cardiac output in any group. Promethazine increased maternal heart rate (p = 0.0001) in both the magnesium sulfate-promethazine and saline solution-promethazine groups. Magnesium sulfate increased uterine blood flow (p less than 0.01) in both the magnesium sulfate-promethazine and magnesium sulfate-saline solution groups, but promethazine blunted the increase in uterine blood flow associated with magnesium sulfate. Similarly, magnesium sulfate decreased uterine vascular resistance (p less than 0.01) in both the magnesium sulfate-promethazine and magnesium sulfate-saline solution groups, but promethazine eliminated the decrease in uterine vascular resistance associated with magnesium sulfate. Maternal and fetal arterial blood gas and acid-base values did not change in any group, except that there was a small, near-significant decrease (p = 0.06) in fetal pH 10 minutes after promethazine was given in the magnesium sulfate-promethazine group. We conclude that magnesium sulfate and promethazine did not interact to cause maternal hypotension in normovolemic gravid ewes. However, promethazine increased maternal heart rate and blunted the increase in uterine blood flow associated with magnesium sulfate.

Animals↗
PubMed1990

Histamine synthesis and catabolism in various tissues in diabetic rats.

In view of the observations that (1) plasma histamine concentrations are significantly higher in diabetic patients and diabetic rats than those in controls, and (2) tissue concentrations of histamine are elevated in rats with experimental diabetes, we have investigated histamine synthesis, as reflected by histidine decarboxylase (HDC) activity, and histamine catabolism, as reflected by histaminase activity, in various tissues of the diabetic rat. Rats with streptozotocin-induced diabetes mellitus (DM) showed an increase in histamine synthesis in various tissues; this was most marked in the aorta and to a lesser, but significant, extent in the kidneys, lungs, and heart, but not in the brain, stomach, or skin. Tissue content of histamine was significantly increased in all tissues except the stomach and skin. We conclude that tissue histamine synthesis is significantly increased in diabetic animals and that this increase is most marked in the aorta. The elevation in HDC activity in these tissues probably accounts for the increase in tissue and plasma concentrations of histamine in diabetic animals, since there is no change in histamine catabolism. This increase in histamine synthesis and release may contribute to the pathogenesis of endothelial damage in diabetic microangiopathy and macroangiopathy.

Animals↗
PubMed1990

Effect of the antiinflammatory prodrug, nabumetone and its principal active metabolite on rat gastric mucosal, aortic and platelet eicosanoid synthesis, in vitro and ex vivo.

Nabumetone is a novel non-steroidal antiinflammatory drug which although a weak cyclooxygenase inhibitor is converted by the liver to metabolites that are more potent inhibitors of cyclooxygenase. Nabumetone may thus avoid the occurrence of prostanoid-mediated gastropathy while maintaining its efficacy as an antiinflammatory agent. We compared the effect of nabumetone and 6-methoxy-2-naphthylacetic acid (6-MNA; the principal active metabolite of nabumetone) with that of naproxen and indomethacin on the synthesis of rat gastric prostaglandins I2 and E2, in vitro and ex vivo. Ex vivo platelet TXA2 and aortic PGI2 synthesis was also investigated in order to assess peripheral activity of nabumetone metabolites. In vitro, nabumetone was completely without effect on gastric mucosal prostanoid synthesis, whereas indomethacin, naproxen and 6-MNA (in this order of potency) inhibited prostanoid synthesis. Ex vivo, low dose naproxen and indomethacin (less than 5mg.kg-1) markedly inhibited gastric mucosal prostanoid synthesis at 30 min and 2 h post gavage, whereas nabumetone was without significant effect. Nabumetone administration also resulted in the inhibition of platelet TXA2 synthesis, whereas aortic PGI2 synthesis was unaltered. These data indicate that the administration of nabumetone may avoid NSAID gastropathy by leaving gastric mucosal prostanoid synthesis intact and also that the active metabolite(s) of nabumetone are effective inhibitors of cyclooxygenase in an NSAID-target tissue (platelet). The lack of effect of nabumetone administration on vascular PGI2 synthesis may confer an additional advantage over other NSAIDs, since the inhibition of peripheral PGI2 has been implicated in hypertensive and nephrotoxic side effects of NSAIDs.

Animals↗
PubMed1990

Does ritodrine worsen maternal hypotension during epidural anesthesia in gravid ewes?

The purpose of this study was to determine whether prior administration ritodrine worsens maternal hypotension during epidural anesthesia in gravid ewes. Twenty-four experiments were performed in nine chronically instrumented animals between 0.8 and 0.9 of timed gestation. The experimental sequence included the following: 1) at time-zero, intravenous (iv) administration of ritodrine, 0.004 mg.kg-1.min-1, or normal saline (NS) for 2 h; 2) at 120 min discontinuation of ritodrine, and administration of a 500 ml iv bolus of NS over 15 min; and 3) at 135 min epidural injection of 2% lidocaine or NS. There were three groups of experiments: 1) iv ritodrine-epidural lidocaine (n = 9); 2) iv NS-epidural lidocaine (n = 8); and 3) iv ritodrine-epidural NS (n =7). Epidural injection of lidocaine resulted in a median sensory level of T9 in both the ritodrine-lidocaine and NS-lidocaine groups. At 165 min (i.e., 30 min after the epidural injection of lidocaine), maternal mean arterial pressure was 19 +/- 3% below baseline (P = 0.0001) in the ritodrine-lidocaine group and 22 +/- 7% below baseline (P = 0.0001) in the NS-lidocaine group (NS between groups). At 120 min ritodrine had increased maternal cardiac output 45 +/- 6% above baseline (P = 0.0001) in the ritodrine-lidocaine group and 39 +/- 6% above baseline (P = 0.0001) in the ritodrine-NS group. Cardiac output remained above baseline (P less than 0.01) after epidural injection of lidocaine in the ritodrine-lidocaine group. In contrast, in the NS-lidocaine group cardiac output was 13 +/- 5% below baseline (P = 0.005) at 150 min. Fetal arterial pH did not change significantly in either the ritodrine-lidocaine or ritodrine-NS group.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, Epidural↗
PubMed1990

Nucleus tractus solitarius as mediator of evoked parabrachial cardiovascular responses in the decerebrate rabbit.

1. The present study has assessed the importance of neurones within the nucleus tractus solitarius (NTS) in mediating the cardiovascular response evoked from the parabrachial nucleus (PBN) in the decerebrate rabbit. Microinjection techniques were employed so that the magnitude of the circulatory responses elicited from the PBN could be compared before, and after, kainic acid or bicuculline were microinjected into restricted regions of the NTS. 2. Electrical stimulation of the PBN (both medial and lateral regions) evoked variable changes in heart rate, a pressor response, vasoconstriction in the hindlimb and an increase in renal sympathetic nerve activity. Glutamate injected into these regions of the PBN elicited a similar pattern of response except that a tachycardia was observed consistently. 3. Both electrical and chemical stimulation of restricted regions of the NTS evoked bradycardia and a depressor response together with an increase in femoral vascular conductance and an inhibition of activity in the renal nerve. 4. Chemical lesions placed in these regions of the NTS by microinjecting kainic acid were found to attenuate both the heart rate and arterial blood pressure responses elicited from sites in the medial and lateral PBN using either electrical or chemical stimulation. Equivalent effects were produced on microinjecting the GABAa receptor antagonist bicuculline into the NTS. 5. These data indicate that NTS neurones play a part in mediating the cardiovascular responses that are evoked from the PBN and suggest that the action of the PBN at the level of the NTS is mediated via a GABAergic mechanism.

Animals↗
PubMed1990

Does indomethacin alter the hemodynamic response to magnesium sulfate infusion and hemorrhage in gravid ewes?

The purpose of this study was to determine whether indomethacin alters the maternal and fetal hemodynamic response to magnesium sulfate (MgSO4) infusion and hemorrhage in gravid ewes. We studied seven chronically instrumented animals between 0.8 and 0.9 of timed gestation. The experimental sequence included: 1) at time 0, indomethacin, 2 mg/kg, or vehicle only intravenously (IV) over 5 minutes; 2) at 60 minutes, MgSO4 4 g IV over 5 minutes; 3) at 65 minutes, MgSO4 infusion at 4 g/hour; 4) at 150 minutes, maternal hemorrhage, 20 mL/kg, over 60 minutes; and 5) at 215 minutes, reinfusion of maternal blood over 60 minutes. Each animal was studied with and without indomethacin. Indomethacin, but not vehicle only, transiently increased maternal and fetal mean arterial pressure (MAP), decreased maternal and fetal heart rate, and decreased maternal cardiac output. Magnesium sulfate significantly decreased uterine vascular resistance and increased uterine blood flow both with and without indomethacin. Hemorrhage significantly decreased maternal MAP, heart rate, cardiac output, and uterine blood flow in both groups. The magnitude of each change was similar between the groups. For example, at the end of hemorrhage, maternal MAP was 36 +/- 7% below baseline (P = .0001) with indomethacin and 41 +/- 2% below baseline (P = .0001) in the vehicle-only group (P = not significant between groups). Hemorrhage significantly decreased fetal heart rate, pH, and PO2, and increased fetal MAP and PCO2 in both groups. We conclude that indomethacin did not alter the maternal or fetal hemodynamic response to MgSO4 infusion and hemorrhage in gravid ewes.

Acid-Base Equilibrium↗
PubMed1989

Intravenous administration of d-tubocurarine and pancuronium in fetal limbs.

The purpose of this study was to assess the effects of intravenous administration of d-tubocurarine and pancuronium in fetal lambs. Eighteen experiments were performed in seven chronically instrumented pregnant ewes between 0.8 and 0.9 of timed gestation. Each fetus received 6 ml of study drug intravenously at 1.2 ml/min over 5 minutes (d-tubocurarine 3.0 mg/kg, pancuronium 0.5 mg/kg, or saline solution control). Pancuronium (n = 7) significantly increased both fetal heart rate and mean arterial pressure. d-Tubocurarine (n = 5) significantly decreased both fetal heart rate and mean arterial pressure. Saline solution control (n = 6) did not significantly alter fetal heart rate or mean arterial pressure. The present study suggests that pancuronium is preferable to d-tubocurarine for those intrauterine procedures when an increase in fetal heart rate is desired.

Animals↗