Biomedical subjects

U Lang

Publications and source records attributed to U Lang.

At least 55 records · Page 3Linked to original sources

PubMed1997

Role of cAMP and calcium influx in endothelin-1-induced ANP release in rat cardiomyocytes.

The mechanism of endothelin-1 (ET-1)-induced atrial natriuretic peptide (ANP) release was studied in neonatal rat ventricular cardiomyocytes. These cells expressed a single high-affinity class of ETA receptor (dissociation constant = 54 +/- 18 pM, n = 3), but no ETB receptors. Incubation of cardiomyocytes with ET-1 led to concentration-dependent ANP release and prostacyclin production. ET-1-induced ANP release was affected by neither protein kinase C (PKC) inhibition or downregulation nor by cyclooxygenase inhibition, indicating that ET-1-stimulated ANP secretion is not a PKC-mediated, prostaglandin-dependent process. Furthermore, ET-1 significantly stimulated adenosine 3',5'-cyclic monophosphate (cAMP) production and increased cytosolic calcium concentration in these preparations. Both ET-1-induced calcium influx and ANP release were decreased by the cAMP antagonist Rp-cAMPS, the Rp diastereoisomer of cAMP. Moreover, ET-1-induced ANP secretion was strongly inhibited in the presence of nifedipine as well as in the absence of extracellular calcium. Thus our results suggest that ET-1 stimulates ANP release in ventricular cardiomyocytes via an ETA receptor-mediated pathway involving cAMP formation and activation of a nifedipine-sensitive calcium channel.

Alkaloids↗

PubMed1996

Role of protein phosphatase 2A in the regulation of mitogen-activated protein kinase activity in ventricular cardiomyocytes.

Incubation of cultured, neonatal rat ventricular cardiomyocytes with 100 nM phorbol 12-myristate-13-acetate (PMA) induced a transient suppression of PP2A activity at 5 min, an effect that was reversed after 15 min of exposure to PMA. This inactivation was correlated with a transient increase in the phosphorylation level of the catalytic subunit of PP2A (193 +/- 38% of control levels at 5 min). Simultaneously to the transient inactivation of PP2A, we observed a rapid and reversible phosphorylation of 42-kDa MAP kinase (474 +/- 65% of control levels at 5 min, and 316 +/- 44% at 15 min) in cardiomyocytes treated with PMA. This transient phosphorylation was accompanied by a transient increase in cytosolic MAP kinase activity (209 +/- 17% of control values at 5 min and 125 +/- 7% at 15 min). Okadaic acid (1 microM ) completely blocked the decrease in the phosphorylation level and activity of MAP kinase occurring after 5 min of exposure to PMA. These data demonstrate that PP2A inactivation and MAP kinase activation are very strongly correlated in cardiomyocytes, indicating that PP2A plays a negative modulatory role in the regulation of MAP kinase activity.

Animals↗

PubMed1996

Inhibition of minK protein induced K+ channels in Xenopus oocytes by estrogens.

Previously it was shown that minK protein expression in uterus is regulated by estrogen. In the present study, we were interested in putative direct effects of estrogen on minK protein induced K+ currents (IminK) in Xenopus oocytes. Superfusion with 17-beta-estradiol (1 microM) resulted in an inhibition of minK-induced currents, but had no appreciable effects on the delayed rectifier and inward rectifier K+ channels Kv1.1 and Kir2.1, respectively. The inhibition of IminK by 17-beta-estradiol was concentration-dependent, with an IC50 of approximately 0.5 microM. In the presence of 17-beta-estradiol, the conductance-voltage relationship was shifted to more depolarized potentials. IminK inhibition occurred also in the presence of the estrogen-receptor antagonist tamoxifen, suggesting that a mechanism independent of estrogen receptors is involved. The synthetic estrogen diethylstilbestrol (DES) also inhibited IminK but with a lower affinity (IC50 of 4.5 microM), while cortisol and progesterone had only weak effects on IminK. In summary, the results indicate that estrogens directly inhibit IminK.

Animals↗

PubMed1996

Elevation of nitrate levels in pregnant ewes and their fetuses.

OBJECTIVE: Nitric oxide is a potent vasodilator released by endothelial cells that may play an important role in modulating maternal and fetal vascular tone in normal pregnancy. The current study was designed to evaluate whether plasma or urine nitrite and nitrate (the metabolites of nitric oxide) concentrations are elevated in pregnant compared with those of nonpregnant sheep and whether the nitrate concentrations in the fetal circulation were increased in comparison with the maternal circulation. STUDY DESIGN: Eleven pregnant sheep and seven nonpregnant oophorectomized sheep were instrumented with catheters in the maternal and fetal femoral arteries and veins, uterine and umbilical veins, and amniotic cavity. Blood, urine, and amniotic fluid samples were collected for nitrate determination at least 5 days after surgery. After extraction nitrate was reduced to nitrite and quantitated with the Greiss reagent. RESULTS: Arterial plasma nitrate concentrations in the pregnant sheep were significantly elevated compared with those of nonpregnant sheet (5.0 +/- 0.9 vs 2.5 +/- 0.6 micromol/L, p < 0.05). The urinary nitrate concentrations were also significantly increased in the pregnant sheep compared with those of nonpregnant sheet (89.9 +/- 16.3 vs 23.1 +/- 4.5 nmol/mg creatinine, p < 0.01). Fetal plasma nitrate concentrations were ninefold higher than the maternal nitrate concentrations (43.9 +/- 7 vs 5.0 +/- 0.9 micromol/L, p < 0.01), whereas amniotic fluid concentrations were extremely high (133.8 +/- 13.8 micromol/L, n = 3). No venous-arterial differences were measurable across either the maternal or fetal sides of the placenta. CONCLUSION: Nitrate concentrations in pregnant sheet and their fetuses are increased. The increased nitrate concentrations in the maternal and fetal circulations may reflect the increased nitric oxide synthesis, which may in part mediate the cardiovascular adaptations to normal pregnancy and the low systemic and umbilical vascular resistance in the fetus.

Amniotic Fluid↗

PubMed1996

Stimulation of atrial natriuretic peptide release by neurokinins in neonatal rat ventricular cardiomyocytes.

The effect of substance P (SP) on atrial natriuretic peptide (ANP) release was studied in neonatal rat ventricular cardiomyocytes. Incubation of cells with SP led to a marked increase in ANP secretion, a response accompanied by increases in alpha-type protein kinase C (PKC) in the membranous cell fraction and 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) formation and a small increase in adenosine 3',5'-cyclic monophosphate (cAMP) production. A role for PKC in SP-induced 6-keto-PGF1 alpha formation and ANP release was apparent insofar as the responses were suppressed by PKC inhibitors and in PKC-downregulated cells. Furthermore, SP-induced 6-keto-PGF1 alpha production was strongly correlated with SP-induced ANP secretion (r = 0.91, P < 0.0001, n = 27), suggesting a role for prostaglandins in SP-mediated ANP release. Supporting this, indomethacin abolished SP-induced ANP release, whereas PGE2, PGF2 alpha, and prostacyclin (PGI2) promoted ANP secretion in this system. Both the profile of SP-induced cAMP production and results obtained with prostaglandin antagonists suggest that a prostanoid FP receptor is at the basis of this response. Finally, both neurokinins A and B induced similar ANP responses, whereas cultured cells were found to contain mRNA transcripts coding for both neurokinin NK1 and NK3 receptor subtypes. Overall, these results suggest that SP induces ANP secretion in neonatal ventricular cardiomyocytes through a PKC- and prostaglandin-dependent signaling pathway.

6-Ketoprostaglandin F1 alpha↗

PubMed1996

Skin blood flow influences the transcutaneous PCO2 (tc PCO2) during stress in the guinea pig.

The transcutaneously measured carbon dioxide tension (tc PCO2) allows fetal monitoring in a continuous and non-invasive way. Though tc PCO2 is correlated well with the fetal acid-base balance, rather large variations in tc PCO2 exist. A decreased skin blood flow is known to influence the transcutaneous oxygen tension (tc PO2), and tc PCO2 might be affected in an equal way. During fetal asphyxia skin blood flow is extremely reduced. Thus, tc PCO2 might be affected by fetal asphyxia, which it is supposed to detect. To elucidate the role of reduced skin perfusion on tc PCO2, experiments on acutely instrumented guinea pigs were performed and skin perfusion was changed by injection of catecholamines. During control tc PCO2 was twice as high as the arterial PCO2 due to a reduced skin perfusion. After injection of catecholamines skin blood flow rose, tc PCO2 fell and the arterio-transcutaneous difference in PCO2 decreased. Then skin perfusion decreased and tc PCO2 increased. We conclude, that during stress situations with a low skin perfusion, as the acutely instrumented guinea pig, tc PCO2 is higher than the arterial PCO2 and can be influenced by changes in skin blood flow. These findings are relevant for the interpretation of tc PCO2 recordings during fetal asphyxia, where an extreme vasoconstriction exists.

Animals↗

PubMed1995

Fetal responses to maternal and fetal methamphetamine administration in sheep.

OBJECTIVES: The current study was designed to test the hypothesis that maternally administered methamphetamine decreases fetal PaO2 by reducing uterine blood flow and to determine the cardiovascular and blood gas responses to varying doses of methamphetamine given both to the fetus and the mother. STUDY DESIGN: Nine near-term pregnant sheep were surgically instrumented to measure maternal and fetal blood pressure and heart rate and uterine and umbilical blood flow. Fetal blood gases and pH were determined before and after each dose of methamphetamine. Methamphetamine was administered as intravenous bolus injections (30 to 35 minutes separating administration of each dose) into the maternal femoral vein in increasing doses of 0.03, 0.1, 0.3, and 1.0 mg/kg and on a separate days to the fetus into the hind limb vein as doses of 0.03, 0.1, 0.3, 1.0, and 3.0 mg/kg estimated fetal weight. RESULTS: Maternal methamphetamine administration produced a dose-related increase in maternal and fetal blood pressure and uterine vascular resistance, whereas uterine blood flow decreased in a dose-related fashion. Umbilical blood flow tended to increase slightly, but this did not reach significance. Fetal PaO2 decreased significantly, whereas fetal pH decreased only modestly. Direct fetal administration of methamphetamine produced dose-related increases in fetal blood pressure and umbilical blood flow and a significant decrease in fetal pH but no change in fetal PaO2. CONCLUSIONS: The fetal PaO2 decrease observed after maternal administration of methamphetamine appears to be a result of decreased uteroplacental perfusion, whereas the observed changes in fetal blood pressure and fetal pH appear to be a result of the direct action of methamphetamine on the fetus.

Animals↗

PubMed1995

Multicenter study of lipoprotein(a) and apolipoprotein(a) phenotypes in patients with end-stage renal disease treated by hemodialysis or continuous ambulatory peritoneal dialysis.

Numerous studies have investigated lipoprotein(a) (Lp(a)) plasma concentrations in patients with ESRD, a patient group with an enormous risk for atherosclerosis. The reported differences in Lp(a) between controls and patients vary from a decrease of 49% to an increase of more than 1,000%. However, data are not consistent, mostly because of problems with statistical analysis, and only limited data are available for patients treated by continuous ambulatory peritoneal dialysis (CAPD). To estimate the significance of Lp(a) in ESRD and to demonstrate the statistical pitfalls concerning Lp(a) in case-control studies, a large multicenter study including 702 patients treated by either hemodialysis (HD) (N = 534) or CAPD (N = 168) was conducted, and results were compared with results from 256 healthy controls. Both patient groups showed significantly elevated Lp(a) levels in comparison with controls: 23.4 +/- 25.0 mg/dL (P < 0.005; HD) and 34.6 +/- 38.4 mg/dL (P < 0.0001; CAPD) versus 18.4 +/- 22.8 mg/dL (controls). CAPD patients showed significantly higher Lp(a) values than did patients treated by HD (P < 0.001). The difference between the two treatment groups possibly reflects an overproduction of Lp(a) to compensate for protein losses in CAPD patients. Both treatment groups included significantly more patients with Lp(a) values greater than the 75th percentile (25.6 mg/dL) of the control group (33.9 and 41.7% for HD and CAPD, respectively; P < 0.005). The higher Lp(a) values in patients were not explained by differences in isoform frequencies and the increase in Lp(a) was apolipoprotein(a) type specific: only patients with high-molecular-weight apolipoprotein(a) isoforms showed a significant elevation in Lp(a) levels. The increased plasma concentrations of Lp(a) may contribute to the high risk for atherosclerosis in ESRD, especially in patients treated by CAPD. Finally, it is believed that small sample sizes are responsible for the diverging results in Lp(a) literature.

Adult↗

PubMed1994

Role of prostaglandin-mediated cyclic AMP formation in protein kinase C-dependent secretion of atrial natriuretic peptide in rat cardiomyocytes.

The role of endogenous prostaglandin production in phorbol diester-induced myocardial atrial natriuretic peptide (ANP) secretion was investigated in cultured spontaneously beating ventricular rat cardiomyocytes. Incubation of cells with 4 beta-phorbol 12-myristate 13-acetate (PMA; 0.1 microM) led to a rapid response in ANP release, a response accompanied by increases in cellular prostacyclin (PGI2) production, cyclic AMP (cAMP) formation and spontaneous contraction frequency. Although PMA-induced ANP secretion exhibited the pharmacological profile of a protein kinase C (PKC)-mediated event, the response was abolished in the presence of the cyclo-oxygenase inhibitors indomethacin (10 microM) and diclofenac (1 microM), indicating that endogenous prostaglandin production is responsible for PMA-induced ANP secretion in this system. Confirming this, PMA-induced ANP secretion was strongly correlated with endogenous formation of 6-oxo-prostaglandin F1 alpha (r = 0.93, P < 0.0005, n = 11), and exogenously applied PGI2, prostaglandin E2 (PGE2) or prostaglandin F2 alpha (PGF2 alpha) elicited simultaneous increases in cAMP formation, contraction frequency and ANP secretion in these cells. Furthermore, PMA-induced cAMP formation was abolished in the presence of either diclofenac or indomethacin, whereas the cAMP-elevating agent forskolin (0.1 microM) mimicked the secretory and chronotropic effect of PMA in these cells. A role for cAMP in PMA-induced ANP secretion was also apparent insofar as PMA-induced ANP release was substantially decreased in the presence of the Rp-diastereomer of 3',5'-cyclic adenosine monophosphorothioate (Rp-cAMPS; 10 microM), whereas the cAMP-mimetic agent dibutyryl cAMP (10 microM) provoked a rapid increase in ANP secretion in this system. Finally, the Ca(2+)-channel antagonist nifedipine (0.1 microM) severely decreased PGI2-, PGE2- and PMA-induced ANP secretion without affecting PGF2 alpha-induced peptide release, suggesting that PGI2 and/or PGE2, but not PGF2 alpha, are the prostanoids involved in PMA-induced ANP release. Taken together, these results suggest that PKC activation induces ANP secretion in spontaneously beating rat ventricular cardiomyocytes via an autocrine pathway involving increased PGI2 and/or PGE2 formation, a response leading to the activation of a myocardial adenylate cyclase and, subsequently, to that of a nifedipine-sensitive Ca2+ channel.

6-Ketoprostaglandin F1 alpha↗

PubMed1994

Protein kinase C-dependent prostaglandin production mediates angiotensin II-induced atrial-natriuretic peptide release.

The respective roles of protein kinase C (PKC) and endogenous prostaglandin formation in angiotensin II (Ang II)-induced myocardial secretion of atrial natriuretic peptide (ANP) was studied in cultured, spontaneously beating, neonatal-rat cardiomyocytes. Incubation of cardiomyocytes with 0.1 microM Ang II led to a rapid but transient increase in particulate-bound PKC activity, a response accompanied by marked increases in cellular 6-oxo-prostaglandin F1 alpha (6-oxo-PGF1 alpha) generation and ANP secretion. A role for PKC in Ang II-induced 6-oxo-PGF1 alpha formation and ANP secretion was apparent, insofar as both responses were suppressed in the presence of the PKC inhibitors staurosporine (1 microM) and CGP 41251 (1 microM), as well as in cells in which PKC had been previously down-regulated by pretreatment with phorbol diester. Furthermore, Ang II-induced 6-oxo-PGF1 alpha production was found to be strongly correlated with Ang II-induced ANP release (r = 0.87, P < 0.001, n = 6), indicating a role for prostacyclin (PGI2) in Ang II-induced ANP secretion in these cells. This hypothesis was confirmed by finding that both Ang II-induced 6-oxo-PGF1 alpha production and ANP release were abolished in the presence of the respective phospholipase A2 and cyclo-oxygenase inhibitors quinacrine (10 microM) and indomethacin (10 microM), whereas exogenously applied PGI2 (1 microM) and prostaglandin E2 (0.1 microM) mimicked Ang II-induced ANP secretion in this system. Taken together, these results suggest that Ang II induces ANP secretion in spontaneously beating rat cardiomyocytes via a PKC-dependent autocrine pathway involving a cyclo-oxygenase product and a yet-to-be-identified myocardial prostanoid receptor.

6-Ketoprostaglandin F1 alpha↗

PubMed1994

[Long-term animal experiment analysis of the use of resorbable staple sutures in partial gastrectomy].

In animal experiments with a 12-month follow-up, the safety and compatibility of absorbable staple lines following gastrointestinal surgery were analysed. In two groups of pigs, partial gastrectomies with gastroduodenostomy (Billroth I, n = 10) or gastrojejunostomy (Roux-en-Y, n = 12) were performed, and Lactomer-a copolymer of glycolic acid and lactic acid-staple lines were used for closure of the lesser curvature of the stomach and the duodenal stump. Application of the staple lines caused no problems and was safe. In 1 of the 22 pigs, which died of an ileus 9 days postoperatively a suture dehiscence (4.5%) at the lesser curvature of the stomach was observed. Macroscopic examination showed no major inflammation around the staples. Microscopically complete absorption of the Lactomer staples without extensive scarification in the gastrointestinal wall could be demonstrated 12 months postoperatively. Our results yielded no contraindications for the clinical use of absorbable staple lines in gastrointestinal surgery. The manufacturer has given advance notice of smaller staples, which it is considered will be an advantage.

Absorption↗

PubMed1994

Calcium influx in platelet activating factor-induced atrial natriuretic peptide release in rat cardiomyocytes.

Atrial natriuretic peptide (ANP) is released from the myocardium after the activation of protein kinase C and/or ischemia, events that are associated with an increase in platelet activating factor (PAF) production in this tissue. In this study we demonstrate that PAF, but not lyso-PAF, induces a concentration-dependent increase in ANP secretion in spontaneously beating neonatal rat cardiomyocytes, a response associated with increases in cellular adenosine 3',5'-cyclic monophosphate (cAMP) formation, calcium influx, and the mobilization of calcium from intracellular stores. cAMP formation and calcium influx appear to play major roles in PAF-induced ANP secretion in this system, insofar as PAF-induced ANP release was substantially reduced in the presence of the (R)-p-diastereoisomer of adenosine 3',5'-cyclic monophosphorothioate (10 microM), whereas both PAF-induced calcium influx and ANP secretion were abolished in the presence of the calcium channel antagonist nifedipine (0.1 microM). Consistent with these results, N6-2'-O-dibutyryl cAMP (DBcAMP, 10 microM) and/or forskolin (0.1 microM) simultaneously increased cAMP production, calcium influx, and ANP release in these cells, with both DBcAMP- and forskolin-induced ANP secretion being fully abolished in the presence of 0.1 microM nifedipine. Taken together, these results suggest that PAF, DBcAMP, and forskolin promote ANP secretion in spontaneously beating cardiomyocytes via the activation of a cAMP-dependent, nifedipine-sensitive myocardial calcium channel and that calcium influx is a major requirement for cAMP-induced ANP secretion in this system.

Animals↗

PubMed1994

[Ca2+]i and protein kinase C in vasopressin-induced prostacyclin and ANP release in rat cardiomyocytes.

Exposure of cultured, spontaneously beating rat cardiomyocytes to arginine vasopressin (AVP) led to marked increases in the release of prostacyclin (PGI2) and atrial natriuretic peptide (ANP). These responses were accompanied by a rapid, transient rise of cytosolic free Ca2+ concentration ([Ca2+]i) and of membranous protein kinase C (PKC) activity. Ca2+ influx and PKC activity appeared to play important but distinct roles in AVP-induced cellular responses, insofar as only AVP-induced ANP secretion was abolished by the Ca2+ channel antagonist nifedipine, whereas both AVP-induced PGI2 production and ANP release were abolished by the PKC inhibitors staurosporine and CGP-41251. The AVP-induced increase in [Ca2+]i could also be mimicked with the vasopressin (V1-subtype) agonist Octapressin, but not with the V2-agonist 1-desamino-8-D-arginine vasopressin, and was fully abolished by the V1-antagonist [d(CH2)5Tyr(Me)]AVP, but not by d(CH2)5-D-Leu-VAVP (V1-/V2-antagonist). These results indicate that V1-vasopressinergic receptors mediate AVP-induced PGI2 production and ANP secretion in rat cardiomyocytes and that, whereas both Ca2+ influx and PKC activation are required for AVP-induced ANP secretion, AVP-induced PGI2 formation is mainly regulated by PKC.

Alkaloids↗

PubMed1993

Transcutaneous PCO2 during labor--a comparison with fetal blood gas analysis and transcutaneous PO2.

Reduction of lethal and compromised fetal outcome is a benefit of rising socio-economic standards and better health care, including technologies such as cardiotocography and fetal blood analysis. The pursuit of higher standards in obstetrics leads to new and improved techniques. The transcutaneously measured carbon dioxide tension (tc PCO2) was proposed as a continuous and non-invasive method revealing the acid-base status of the fetus. Nonetheless, intrapartum surveillance by measuring tc PCO2 is rarely used in clinical practice. To assess the value of fetal monitoring by tc PCO2 during parturition, tc PCO2 measurements were compared with the fetal acid-base status. Tc PCO2 was measured by a recently developed electrode during 21 deliveries. The tc PCO2 electrode was disinfected, calibrated and applied to the presenting part of the fetus after rupture of membranes. The acid-base status of the fetus was determined with a commercial blood gas analyser in capillary blood (n = 33) and umbilical artery samples (n = 15). Tc PCO2 was correlated with the PCO2 of the capillary blood (r = 0.56; n = 33; P < 0.001) as well as with the PCO2 in the umbilical artery (r = 0.75; n = 15; P < 0.01). The pH value of capillary blood was related to tc PCO2 (r = -0.56; n = 33; P < 0.001). However, tc PCO2 did not show a significant relation with the pH value in the umbilical artery (r = -0.34; n = 15). Variations in skin blood flow are known to decrease the transcutaneously measured oxygen tension (tc PO2) below the PO2 in the capillary and umbilical blood.(ABSTRACT TRUNCATED AT 250 WORDS)

Arteries↗

PubMed1993

Protein kinase C-mediated phospholipase A2 activation, platelet-activating factor generation and prostacyclin release in spontaneously beating rat cardiomyocytes.

The expression of protein kinase C (PKC) isoenzymes and the effects of PKC activation on myocardial phospholipase A2 (PLA2) activity, platelet-activating factor (PAF) generation and eicosanoid release were studied in spontaneously beating cultured rat cardiomyocytes. Western blotting analysis indicated that these cells contain PKC alpha, beta, delta and zeta, but not PKC gamma or epsilon. Stimulation of cardiomyocytes with 4 beta-phorbol 12-myristate 13-acetate (PMA) led to a rapid increase in particulate-bound PKC activity, a response attributed to the activation of alpha-, delta- and zeta- type PKCs but not beta-type PKC. Translocation of PKC alpha, delta and zeta was accompanied by simultaneous increases in cellular lysophosphatidylcholine (lyso-PC), PAF, 15(S)-hydroxy-5,8,-11,13-eicosatetraenoic acid (15-HETE), prostaglandin E2 (PGE2) and prostacyclin (PGI2) generation, suggesting that one or more of these isoenzymes directly or indirectly activates a PLA2 in these cells. Confirming this, 4 beta-phorbol 12-monoacetate and 4 alpha-phorbol had no effect on cellular eicosanoid formation, while the PMA-induced response was fully abolished both in the presence of the PKC inhibitors staurosporine and CGP 41251 and in PKC-down-regulated cells. PKC alpha, delta and/or zeta therefore appear to play an important role in the PMA-mediated activation of cardiomyocyte PLA2, an event leading to subsequent production of PGI2, PGE2, 15-HETE, lyso-PC and PAF in this tissue.

Animals↗

PubMed1993

Autonomic modulation of insulin levels in foetal sheep.

The autonomic nervous system plays an important part in metabolic and circulatory adaptation of the foetus to changes in its intrauterine environment and after delivery. Foetal and neonatal glucose metabolism and insulin secretion are influenced by changes in humoral catecholamine levels as they may occur during asphyxia. To assess the role of neuronal and humoral sympathetic activity in foetal endocrine pancreatic regulation, chronically catheterized foetal sheep near term were chemically sympathectomized with 6-hydroxydopamine. Experiments were carried out in unanaesthetized foetal sheep in utero in the absence of uterine contractions. Insulin and glucose levels, blood gases, acid-base status and catecholamines were measured before, during and after a 2 min occlusion of uterine blood flow caused by mechanical constriction of the maternal aorta. Pancreatic blood flow was determined using radioactive labelled microspheres. During normoxaemia, insulin levels, pancreatic blood flow and glucose transport to the organ in sympathectomized foetuses were elevated compared with intact animals, whereas glucose concentrations did not show any significant differences. After the onset of asphyxia humoral catecholamine levels rose significantly in both groups. Insulin concentrations in the plasma of both intact and sympathectomized foetuses were no longer different indicating both indirect (blood flow and humoral catecholamine related) and direct (neurally mediated) sympathetic effects on pancreatic beta cells.

Animals↗

PubMed1993

Maternal and fetal cardiovascular responses to methamphetamine in the pregnant sheep.

OBJECTIVES: Our purpose was to evaluate the maternal and fetal cardiovascular effects of maternally administered methamphetamine and to determine the extent of placental transfer. STUDY DESIGN: Seven near-term pregnant sheep were surgically instrumented to measure maternal and fetal blood pressure and heart rate, cardiac output, uterine flow, and umbilical flow. A single dose of methamphetamine 1 mg/kg was administered as a bolus to study maternal and fetal cardiovascular responses and placental transfer. RESULTS: Maternal administration of methamphetamine caused increases in maternal blood pressure, heart rate, cardiac output, and systemic vascular resistance and decreased uterine blood flow. Peak maternal changes occurred within 10 minutes after methamphetamine administration and were near baseline by 180 minutes. Fetal blood pressure increased and returned slowly to baseline by 2 hours. After an initial decrease fetal heart rate increased above baseline values over the next 2 hours. Umbilical blood flow also decreased initially and then increased slightly. Fetal pH and PO2 tended to decrease. Maternal and fetal methamphetamine levels reached a maximum of 2.9 and 1.9 micrograms/ml, respectively. Rapid and significant placental transfer, delayed excretion into the amniotic fluid, and slow elimination from the maternal and fetal circulation were demonstrated. CONCLUSION: Methamphetamine readily crosses the ovine placenta, producing significant and long-lasting maternal and fetal cardiovascular effects, which may have long-term consequences, especially if administered repetitively.

Amniotic Fluid↗

PubMed1993

Systemic and uterine vascular response to serotonin in third trimester pregnant ewes.

Released from aggregating platelets, serotonin (5HT) among other vasoactive components is considered to play an important role in preeclampsia, one of the most common medical complications of pregnancy. This study was designed to evaluate the simultaneous uterine and systemic vascular effects of systemically administered serotonin in pregnant sheep and compare them to the well known effects of angiotensin II and norepinephrine. Nine instrumented pregnant ewes received intravenous (inferior vena cava) infusions of increasing doses of serotonin, norepinephrine and angiotensin II in random order. Cardiac output, arterial blood pressure, heart rate, and uterine blood flow were recorded. Systemic administration of serotonin at doses of 2, 4, and 8 micrograms/kg body weight/min caused a slight increase in mean arterial blood pressure (1, 4 and 11%), a large decrease in uterine blood flow (10, 37, and 71%) but did not change cardiac output. Serotonin led to an increase in uterine vascular resistance with only small changes in systemic vascular resistance (UVR 17, 107, and 363% vs. SVR 3, 10 and 11%). In contrast, angiotensin II increased both systemic and uterine vascular resistance (SVR 16, 37, 56, and 95% and UVR 5, 16, 28 and 99%). Norepinephrine also raised both systemic and uterine vascular resistance, though to a different extent (SVR 5, 17, 37, and 118% vs. UVR 5, 46, 84 and 304%). Systemic infusions of serotonin in third trimester pregnant ewes resulted in uterine vasoconstriction. In contrast to the marked effect on the uterine vasculature, the systemic cardiovascular responses were small, thus demonstrating a nearly selective effect of serotonin on the uterine vasculature at the doses administered.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗