Umbilical and hepatic venous responses to circulating vasoconstrictive hormones in fetal lamb

1991 ◽  
Vol 260 (4) ◽  
pp. H1205-H1213 ◽  
Author(s):  
R. P. Paulick ◽  
R. L. Meyers ◽  
C. D. Rudolph ◽  
A. M. Rudolph
Keyword(s):  
Blood Flow ◽  
Angiotensin Ii ◽  
Vascular Resistance ◽  
Ductus Venosus ◽  
Dependent Manner ◽  
Outflow Resistance ◽  
Fetal Sheep ◽  
Descending Aorta ◽  
Placental Blood ◽  
Dose Dependent

Acute fetal hypoxemia increases the vascular resistance of the umbilical veins as well as that of the liver. Because, at least in the human, the umbilical-placental circulation has no autonomic innervation, circulating hormones could well be responsible for this increase in umbilical-placental outflow resistance. In chronically instrumented fetal sheep, norepinephrine, epinephrine, vasopressin, and angiotensin II were infused in sequentially increasing doses into the descending aorta and vascular resistance to umbilical-placental blood flow was measured. Norepinephrine and epinephrine increased the vascular resistance of the umbilical veins in a dose-dependent manner. Both catecholamines also increased the vascular resistance of the liver, resulting in an increase in ductus venosus blood flow. In contrast, vasopressin and angiotensin II had no effect on umbilical-placental outflow resistance. Thus catecholamines may be responsible for the increase in the vascular resistance of the umbilical veins and liver in response to acute fetal hypoxemia.

Angiotensin II and alpha-agonist. I. Responses of ovine fetoplacental vasculature

1990 ◽  
Vol 259 (2) ◽  
pp. H464-H472 ◽  
Author(s):  
T. Yoshimura ◽  
R. R. Magness ◽  
C. R. Rosenfeld
Keyword(s):  
Blood Flow ◽  
Angiotensin Ii ◽  
Vascular Resistance ◽  
Plasma Catecholamines ◽  
Ang Ii ◽  
Adrenergic Stimulation ◽  
Umbilical Blood ◽  
Steady State Responses ◽  
Maternal Responses ◽  
Dose Dependent

During ovine pregnancy the uteroplacental vasculature is less responsive to angiotensin II (ANG II)-induced vasoconstriction than the systemic vasculature, whereas responses to alpha-agonists are just the opposite. Comparisons of fetal systemic and placental vascular responses to these agents are not well described, nor have they been compared with maternal responses. We determined steady-state responses to fetal infusions (5-7 min) of ANG II (0.023-5.73 micrograms/min) and phenylephrine (PHEN, 0.031-7.64 micrograms/min), continuously monitoring mean arterial pressure (MAP), heart rate (HR), and umbilical blood flow (UmBF). Although both vasoconstrictors caused dose-dependent increases in MAP and umbilical vascular resistance (UmVR), responsiveness (delta MAP and delta UmVR) to ANG II (mol/min) was 35- to 60-fold greater than to PHEN. ANG II caused dose-dependent decreases in UmBF (2-48%); PHEN had minimal effects except at the highest dose, UmBF decreasing only 18%. Although patterns of fetal responses of MAP, UmBF, and UmVR to ANG II resembled maternal responses of MAP and uterine blood flow and uterine vascular resistance, the former were greatly attenuated. Similar observations were made with PHEN for UmBF and UmVR but not MAP. ANG II is a more potent fetal systemic and placental vasoconstrictor than PHEN; however, compared with those of the mother the responses are attenuated. Moreover, the fetoplacental vascular bed appears unresponsive to alpha-adrenergic stimulation, possibly reflecting a mechanism for maintaining UmBF when plasma catecholamines are elevated.

Vasomotor responses of the umbilical circulation in fetal sheep

1989 ◽  
Vol 256 (5) ◽  
pp. R1056-R1062 ◽  
Author(s):  
S. L. Adamson ◽  
R. J. Morrow ◽  
S. B. Bull ◽  
B. L. Langille
Keyword(s):  
Angiotensin Ii ◽  
Vascular Resistance ◽  
Fluid Transport ◽  
Venous Pressure ◽  
Fold Increase ◽  
Vasoactive Agents ◽  
Fetal Sheep ◽  
Placental Blood ◽  
Umbilical Arteries ◽  
Placental Blood Flow

The effects of vasoactive agents on the distribution of vascular resistance within the umbilical circulation of fetal sheep in utero has been assessed under general anesthesia. Under control conditions, 37% of the arterial to venous pressure drop occurred across the umbilical arteries and their major tributaries, 8% occurred across umbilical veins, and the remaining 55% occurred across the cotyledons. Isoproterenol had no significant effect on these resistances. Norepinephrine and angiotensin II both dramatically increased placental vascular resistance, but the distribution of resistances was altered in different ways. Angiotensin caused a 13-fold increase in the umbilical arterial resistance, whereas there were no changes in cotyledon or venous resistances. Norepinephrine also had no effect on cotyledon vascular resistance but it constricted downstream vessels (6-fold increase). These results suggest that norepinephrine and angiotensin II regulate fetal placental blood flow and that they can independently control pressure in placental exchange vessels. As a consequence, these agents may play an important role in controlling fetal-maternal fluid transport.

Uterine and nonuterine vascular responses to angiotensin II in ovine pregnancy

1989 ◽  
Vol 257 (1) ◽  
pp. H17-H24 ◽  
Author(s):  
C. R. Rosenfeld ◽  
R. P. Naden
Keyword(s):  
Blood Flow ◽  
Angiotensin Ii ◽  
Vascular Resistance ◽  
Ang Ii ◽  
Uterine Blood Flow ◽  
Blood Flows ◽  
Pregnant Sheep ◽  
Regional Blood Flows ◽  
Dose Dependent ◽  
Systemic Responses

The uteroplacental vasculature is more refractory to angiotensin II (ANG II) than the systemic vasculature as a whole. To ascertain the differences in responses between reproductive and nonreproductive tissues that account for this, we infused ANG II (0.573, 5.73, and 11.5 micrograms/min) in pregnant sheep (137 +/- 5 days of gestation) and monitored arterial pressure (MAP), heart rate, and uterine blood flow (UBF); cardiac output and regional blood flows were measured with radiolabeled microspheres. Dose-dependent changes in MAP, UBF, and systemic (SVR) and uterine (UVR) vascular resistance occurred (P less than 0.05); systemic responses exceeded uterine (P less than 0.05), except with 11.5 micrograms/min, when % delta UVR = % delta SVR, % delta UVR greater than % delta MAP, and UBF fell 29%. Although a dose-dependent rise in placental resistance occurred, blood flow was unaffected except at 11.5 micrograms ANG II/min, falling 16.8 +/- 3.5% (P = 0.059). In contrast, endometrial perfusion decreased 68 +/- 4.2 and 81 +/- 1.8% (P less than 0.01) with 5.73 and 11.5 micrograms ANG II/min, respectively. Myometrial responses were intermediate, thus placental flow increased from 75 to greater than 90% of total UBF. Adipose, renal, and adrenal glands were extremely sensitive to ANG II, with blood flows decreasing maximally at 0.573 micrograms/min (P less than 0.05). Maximum adipose vascular resistance occurred at 0.573 micrograms/min, greater than 400% (P less than 0.001), exceeding responses in all tissues (P less than 0.05). The placenta is less responsive to ANG II than other uterine and most nonreproductive tissues, resulting in preferential maintenance of uteroplacental perfusion and protecting the fetus from the effects of this vasoconstrictor.

Effects of NO-Donors on Thrombus Formation and Microcirculation in Cerebral Vessels of the Rat

1996 ◽  
Vol 76 (01) ◽  
pp. 111-117 ◽  
Author(s):  
Yasuto Sasaki ◽  
Junji Seki ◽  
John C Giddings ◽  
Junichiro Yamamoto
Keyword(s):  
Blood Flow ◽  
Thrombus Formation ◽  
Dependent Manner ◽  
Red Cell ◽  
Cell Velocity ◽  
Red Cell Velocity ◽  
The Mean ◽  
Wall Shear ◽  
Dose Dependent

SummarySodium nitroprusside (SNP) and 3-morpholinosydnonimine (SIN-1), are known to liberate nitric oxide (NO). In this study the effects of SNP and SIN-1 on thrombus formation in rat cerebral arterioles and venules in vivo were assessed using a helium-neon (He-Ne) laser. SNP infused at doses from 10 Μg/kg/h significantly inhibited thrombus formation in a dose dependent manner. This inhibition of thrombus formation was suppressed by methylene blue. SIN-1 at a dose of 100 Μg/kg/h also demonstrated a significant antithrombotic effect. Moreover, treatment with SNP increased vessel diameter in a dose dependent manner and enhanced the mean red cell velocity measured with a fiber-optic laser-Doppler anemometer microscope (FLDAM). Blood flow, calculated from the mean red cell velocity and vessel diameters was increased significantly during infusion. In contrast, mean wall shear rates in the arterioles and venules were not changed by SNP infusion. The results indicated that SNP and SIN-1 possessed potent antithrombotic activities, whilst SNP increased cerebral blood flow without changing wall shear rate. The findings suggest that the NO released by SNP and SIN-1 may be beneficial for the treatment and protection of cerebral infarction

Modulation of Ca2+ transients in neonatal and adult rat cardiomyocytes by angiotensin II and endothelin-1

1996 ◽  
Vol 270 (3) ◽  
pp. H857-H868 ◽  
Author(s):  
R. M. Touyz ◽  
J. Fareh ◽  
G. Thibault ◽  
B. Tolloczko ◽  
R. Lariviere ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Receptor Agonist ◽  
Dependent Manner ◽  
Induced Responses ◽  
Ang Ii ◽  
Binding Studies ◽  
Vasoactive Peptides ◽  
Adult Cardiomyocytes ◽  
Etb Receptor ◽  
Dose Dependent

Vasoactive peptides may exert inotropic and chronotropic effects in cardiac muscle by modulating intracellular calcium. This study assesses effects of angiotensin II (ANG II) and endothelin-1 (ET-1) on intracellular free calcium concentration ([Ca2+]i) in cultured cardiomyocytes from neonatal and adult rats. [Ca2+]i was measured microphotometrically and by digital imaging using fura 2 methodology. Receptor subtypes through which these agonists induce responses were determined pharmacologically and by radioligand binding studies. ANG II and ET-1 increased neonatal atrial and ventricular cell [Ca2+]i transients in a dose-dependent manner. ANG II (10(-11) to 10(-7) M) failed to elicit [Ca2+]i responses in adult cardiomyocytes, whereas ET-1 increased [Ca2+]i in a dose-dependent manner. The ETA receptor antagonist BQ-123 significantly reduced (P 7< 0.05) ET-1 induced responses, and the ETB receptor agonist IRL-1620 (10(-7) to 10(-5) M) significantly increased (P < 0.05) [Ca2+]i in neonatal and adult cardiomyocytes. ET-1 binding studies demonstrated 85% displacement by BQ-123 and approximately 15% by the ETB receptor agonist sarafotoxin S6c, suggesting a predominance of ETA receptors. Competition binding studies for ANG II failed to demonstrate significant binding on adult ventricular myocytes, indicating the absence or presence of very few ANG II receptors. These data demonstrate that ANG II and ET-1 have stimulatory [Ca2+]i effects on neonatal cardiomyocytes, whereas in adult cardiomyocytes, ANG II-induced effects are insignificant, and only ET-1-induced responses, which are mediated predominantly via ETA receptors, are preserved. Cardiomyocyte responses to vasoactive peptides may thus vary with cardiac development.

scholarly journals Blockade of Cerebral Blood Flow Response to Insulin-Induced Hypoglycemia by Caffeine and Glibenclamide in Conscious Rats

1997 ◽  
Vol 17 (12) ◽  
pp. 1309-1318 ◽  
Author(s):  
Naoaki Horinaka ◽  
Tang-Yong Kuang ◽  
Hazel Pak ◽  
Robert Wang ◽  
Jane Jehle ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Degradation Products ◽  
Dependent Manner ◽  
Conscious Rats ◽  
Intravenous Injections ◽  
Adenosine Receptor Antagonist ◽  
Flow Response ◽  
Arterial Plasma ◽  
Dose Dependent

The possibility that adenosine and ATP-sensitive potassium channels (KATP) might be involved in the mechanisms of the increases in cerebral blood flow (CBF) that occur in insulin-induced hypoglycemia was examined. Cerebral blood flow was measured by the [14C]iodoantipyrine method in conscious rats during insulin-induced, moderate hypoglycemia (2 to 3 mmol/L glucose in arterial plasma) after intravenous injections of 10 to 20 mg/kg of caffeine, an adenosine receptor antagonist, or intracisternal infusion of 1 to 2 μmol/L glibenclamide, a KATP channel inhibitor. Cerebral blood flow was also measured in corresponding normoglycemic and drug-free control groups. Cerebral blood flow was 51% higher in untreated hypoglycemic than in untreated normoglycemic rats ( P < 0.01). Caffeine had a small, statistically insignificant effect on CBF in normoglycemic rats, but reduced the CBF response to hypoglycemia in a dose-dependent manner, i.e., 27% increase with 10 mg/kg and complete elimination with 20 mg/kg. Chemical determinations by HPLC in extracts of freeze-blown brains showed significant increases in the levels of adenosine and its degradation products, inosine and hypoxanthine, during hypoglycemia ( P < 0.05). Intracisternal glibenclamide had little effect on CBF in normoglycemia, but, like caffeine, produced dose-dependent reductions in the magnitude of the increases in CBF during hypoglycemia, i.e., +66% with glibenclamide-free artificial CSF administration, +25% with 1 μmol/L glibenclamide, and almost complete blockade (+5%) with 2 μmol/L glibenclamide. These results suggest that adenosine and KATP channels may play a role in the increases in CBF during hypoglycemia.

Endothelin-1 vasoactive responses in lambs with pulmonary hypertension and increased pulmonary blood flow

1995 ◽  
Vol 269 (6) ◽  
pp. H1965-H1972 ◽  
Author(s):  
J. Wong ◽  
V. M. Reddy ◽  
K. Hendricks-Munoz ◽  
J. R. Liddicoat ◽  
R. Gerrets ◽  
...  
Keyword(s):  
Blood Flow ◽  
Pulmonary Hypertension ◽  
Pulmonary Vascular Resistance ◽  
Vascular Resistance ◽  
Pulmonary Blood Flow ◽  
Heart Diseases ◽  
Main Pulmonary Artery ◽  
Similar Degree ◽  
Fetal Sheep ◽  
Endothelin 1

Increased concentrations of endothelin-1 (ET-1) are found in children with congenital heart diseases that produce increased pulmonary blood flow and pulmonary hypertension, but the role of ET-1 in the pathophysiology of pulmonary hypertension is unclear. Therefore, we investigated ET-1-induced vasoactive responses and ET-1 concentrations in an animal model of pulmonary hypertension and increased pulmonary blood flow. Vascular shunts were placed between the ascending aorta and main pulmonary artery in seven late-gestation fetal sheep. Four weeks after spontaneous delivery, ET-1 increased pulmonary vascular resistance by 29.7 +/- 34.4% (P < 0.05), the ETb-receptor agonist [Ala1,3,11,15]ET-1 (4AlaET-1) had no effect, and the ETa-receptor antagonist cyclo(D-Asp-L-Pro-D-Val-L-Leu-D-Trp) (BQ-123) decreased pulmonary vascular resistance by -16.0 +/- 5.6% (P < 0.05). In contrast, in six control lambs with a similar degree of pulmonary hypertension induced by U-46619, ET-1 and 4AlaET-1 decreased pulmonary vascular resistance by 24.8 +/- 17.6, and 20.0 +/- 13.8%, respectively (P < 0.05). In addition, systemic arterial concentrations of immunoreactive ET-1 were elevated in lambs with pulmonary hypertension (29.2 +/- 9.6 vs. 15.2 +/- 10.7 pg/ml, P < 0.05). Pulmonary hypertension and increased pulmonary blood flow alters the response of ET-1 from pulmonary vasodilation to vasoconstriction. These altered responses suggest a role for ET-1 and its receptors in the pathogenesis of pulmonary hypertension secondary to increased pulmonary blood flow.

Peripheral chemoreflex activation and cardiac function during hypoxemia in near term fetal sheep without placental compromise

2021 ◽  
Author(s):  
Juulia Lantto ◽  
Tiina Erkinaro ◽  
Mervi Haapsamo ◽  
Heikki Huhta ◽  
Leena Alanne ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Blood Flow ◽  
Carotid Artery ◽  
Arterial Oxygen ◽  
Sheep Model ◽  
Fetal Sheep ◽  
Descending Aorta ◽  
Arterial Blood ◽  
Near Term ◽  
Peripheral Chemoreflex

A drop in arterial oxygen content activates fetal chemoreflex including an increase in sympathetic activity leading to peripheral vasoconstriction and redistribution of blood flow to protect the brain, myocardium, and adrenal glands. By using a chronically instrumented fetal sheep model with intact placental circulation at near-term gestation, we investigated the relationship between peripheral chemoreflex activation induced by hypoxemia and central hemodynamics. 17 Åland landrace sheep fetuses at 115-128/145 gestational days were instrumented. Carotid artery was catheterised in 10 fetuses and descending aorta in 7 fetuses. After a 4-day recovery, baseline measurements of fetal arterial blood pressures, blood gas values, and fetal cardiovascular hemodynamics by pulsed Doppler ultrasonography were obtained under isoflurane-anesthesia. Comparable data to baseline was collected 10 (acute hypoxemia) and 60 minutes (prolonged hypoxemia) after maternal hypo-oxygenation to saturation level of 70-80% was achieved. During prolonged hypoxemia, pH and base excess (BE) were lower, and lactate levels higher in the descending aorta than in the carotid artery. During hypoxemia mean arterial blood pressure (MAP) in the descending aorta increased, while in the carotid artery MAP decreased. In addition, right pulmonary artery pulsatility index values increased, and the diastolic component in the aortic isthmus blood flow velocity waveform became more retrograde. Both fetal ventricular cardiac outputs were maintained even during prolonged hypoxemia when significant fetal metabolic acidemia developed. Fetal chemoreflex activation induced by hypoxemia decreased the perfusion pressure in the cerebral circulation. Fetal weight-indexed LVCO or AoI Net Flow-ratio did not correlate with a drop in carotid artery blood pressure.

Inhibition of angiotensinogen production by angiotensin II analogues in human hepatoma cell line

1989 ◽  
Vol 257 (5) ◽  
pp. C888-C895 ◽  
Author(s):  
E. Coezy ◽  
I. Darby ◽  
J. Mizrahi ◽  
B. Cantau ◽  
M. H. Donnadieu ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Cell Line ◽  
Binding Sites ◽  
Inhibitory Effect ◽  
Hepatoma Cell Line ◽  
Dependent Manner ◽  
Human Hepatoma ◽  
Ang Ii ◽  
Hep G2 ◽  
Dose Dependent

The aim of this study was to examine in Hep G2, a human hepatoma-derived cell line, the presence of angiotensin II (ANG II) receptors and the effect of ANG II and its analogues on angiotensinogen production. The presence of ANG II receptors was demonstrated using a long-acting ANG II analogue, 125I-labeled [Sar1]ANG II. A single class of specific binding sites was identified in these cells with a dissociation constant (Kd) of 2 nM. The number and affinity of these binding sites were not changed by [Sar1]ANG II treatment over 24 h. ANG II showed an inhibitory effect on angiotensinogen production. [Sar1]ANG II also exhibited a similar inhibitory effect as that of ANG II but to a greater extent and therefore was used throughout these studies. [Sar1]ANG II inhibited angiotensinogen production in a dose-dependent manner, exhibiting a half-maximal inhibitory concentration (IC50) of 2 nM. Other ANG II analogues showed similar effects on angiotensinogen production. In order of decreasing ability, they were [Sar1]ANG II greater than [Sar1-Ala8]ANG II greater than [Sar1-Val8]ANG II greater than [Sar1-Val5-(Br5)-Phe8]ANG II greater than [Sar1-Val5-DPhe8]ANG II. Results of these studies show that the Hep G2 cell possesses specific ANG II receptors and that [Sar1]ANG II induces a dose-dependent inhibition of angiotensinogen production in this system.

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