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.

Differential responses of uterine and umbilical vasculatures to angiotensin II and norepinephrine

1990 ◽  
Vol 259 (1) ◽  
pp. H197-H203 ◽  
Author(s):  
K. E. Clark ◽  
G. L. Irion ◽  
C. E. Mack
Keyword(s):  
Blood Flow ◽  
Angiotensin Ii ◽  
Arterial Pressure ◽  
Vascular Resistance ◽  
Base Line ◽  
Ang Ii ◽  
Uterine Blood Flow ◽  
Umbilical Blood ◽  
Arterial Blood ◽  
Pregnant Sheep

Although the uterine vascular responses to endogenous vasoactive substances have been extensively investigated in pregnant sheep, the fetal umbilical responses to angiotensin II (ANG II) and norepinephrine (NE) have not been well characterized. Twenty-five pregnant ewes between 105 and 115 days of gestation were anesthetized and instrumented for hemodynamic measurements, systemic fetal and maternal intravenous infusions, and local maternal uterine arterial infusions of ANG II and NE. Fetal and maternal arterial pressure and heart rate, maternal uterine blood flow (total of left and right middle uterine arteries), and fetoplacental blood flow (common umbilical artery) were measured during continuous infusions of ANG II or NE. Fetal infusions of ANG II (0.03–1.0 micrograms.min-1.kg estimated fetal body wt-1) increased fetal arterial blood pressure by as much as 44% over base-line values, decreased umbilical blood flow by as much as 63%, and increased umbilical vascular resistance by up to 345%. Fetal infusions of NE (0.1–3 micrograms.min-1.kg-1) increased fetal arterial pressure 42% and increased umbilical vascular resistance by up to 38% but did not significantly alter fetoplacental blood flow. No significant maternal changes were observed during fetal infusions. Maternal infusion of ANG II increased maternal arterial pressure by as much as 59% and significantly increased uterine vascular resistance at the two highest doses but significantly decreased uterine blood flow only at the highest dose (17%; P less than 0.05). Maternal infusions of NE increased arterial pressure by as much as 113%, decreased uterine blood flow by as much as 76%, and increased uterine vascular resistance 3- to 10-fold over the base-line value.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

Uterine prostaglandin production in ovine pregnancy: effects of angiotensin II and indomethacin

1992 ◽  
Vol 263 (1) ◽  
pp. H188-H197 ◽  
Author(s):  
R. R. Magness ◽  
C. R. Rosenfeld ◽  
D. J. Faucher ◽  
M. D. Mitchell
Keyword(s):  
Angiotensin Ii ◽  
Ang Ii ◽  
Uterine Blood Flow ◽  
Prostaglandin Production ◽  
Eicosanoid Production ◽  
Pregnant Sheep ◽  
Vascular Responsiveness ◽  
Vascular Beds ◽  
Systemic Responses

The ovine and human uteroplacental vascular beds are more refractory to angiotensin II (ANG II)-induced vasoconstriction than the systemic vasculature. ANG II increases in vitro prostacyclin (PGI2) production by uterine but not omental arteries from pregnant sheep. Thus vasodilator prostaglandins may account for this difference in vascular responsiveness. We measured uterine and systemic eicosanoid production and hemodynamic responses in pregnant sheep before and during intravenous ANG II (1.15 and 11.5 micrograms/min). ANG II caused dose-related increases in arterial pressure and systemic and uterine vascular resistance (P less than 0.05). PGI2 metabolite (6-keto-PGF1 alpha) in the uterine vein rose from 166 +/- 70 (SE) to 223 +/- 114 and 631 +/- 323 pg/ml, respectively (P less than 0.05), and arterial levels increased from 67 +/- 24 to 145 +/- 78 and 312 +/- 173 pg/ml, respectively (P less than 0.05). Basal uterine venoarterial differences of 6-keto-PGF1 alpha were 99 +/- 43 pg/ml and increased during 11.5 micrograms ANG II/min to 295 +/- 181 pg/ml (P less than 0.05) but not during 1.15 micrograms/min (64 +/- 30 pg/ml). Responses were similar in gravid and nongravid uterine horns. Unilateral uterine prostaglandin inhibition with indomethacin did not alter basal uterine blood flow or systemic responses to ANG II (0.573-11.5 micrograms/min); however, ipsilateral uterine prostaglandin production fell and uterine vasoconstrictor responses increased (P less than 0.05). During ovine pregnancy ANG II increases uterine PGI2 production. PGI2 appears in part to attenuate ANG II-induced uterine vasoconstriction.

Effect of prostaglandin E2 on ovine maternal placental blood flow

1976 ◽  
Vol 231 (3) ◽  
pp. 754-759 ◽  
Author(s):  
JH Rankin ◽  
TM Phernetton
Keyword(s):  
Blood Flow ◽  
Renal Blood Flow ◽  
Placental Transfer ◽  
Venous Catheter ◽  
Uterine Blood Flow ◽  
Blood Flows ◽  
Pregnant Sheep ◽  
Maternal Brain ◽  
Regional Blood Flows ◽  
Near Term

The effect of PGE2 on regional blood flows in the chronically catheterized near-term pregnant sheep was investigated using radioactive microspheres. The injection of 20 mug PGE2 per kilogram into the left ventricle of eight sheep resulted in no change in maternal brain and noncotyledonary uterine flow. The renal blood flow increased from 692 to 892 ml/min (P less than 0.004). The uterine blood flow decreased from 673 to 317 ml/min (P less than 0.001). The trium was bypassed by injecting 7 mug PGE2 per kilogram of sheep into a fetal venous catheter and permitting it to reach the placental vasculature after placental transfer. Eleven sets of observations were made in eight animals. We observed no change in the intrauterine pressure, maternal brain flow, and noncotyledonary uterine blood flow secondary to this procedure. The maternal renal blood flow changed from 592 to 669 ml/min (P less than 0.007). The uterine blood flow increased from 762 to 853 ml/min (P less than 0.02). The uterine vascular resistance decreased from 0.124 to 0.115 mmHg x min/ml (P less than 0.04). It was concluded that 1) PGE3 crosses the placenta quite readily, and 2) PGE3 causes dilatation of the maternal placental vascular bed.

Regional blood flow and vascular resistance in response to oxytocin in the pregnant sheep and dog

1961 ◽  
Vol 16 (6) ◽  
pp. 1087-1092 ◽  
Author(s):  
N. S. Assali ◽  
L. Holm ◽  
H. Parker
Keyword(s):  
Blood Flow ◽  
Vascular Resistance ◽  
Regional Blood Flow ◽  
Uterine Blood Flow ◽  
Pregnant Uterus ◽  
Blood Flows ◽  
Uterine Contractions ◽  
Intravenous Drip ◽  
Pregnant Sheep ◽  
Regional Vascular Resistance

The effects of oxytocin on regional blood flow and regional vascular resistance were investigated in a group of pregnant ewes and bitches not in labor and in another group in early labor. Single injections or intravenous drip infusion did not change significantly arterial pressure, cardiac output, electrocardiogram, and renal, iliac, femoral, and carotid blood flows in any of the animals studied. The effects on the pregnant uterus were negligible before the onset of spontaneous labor. Only when the animal was in labor did oxytocin produce an increase in uterine contractions accompanied by a significant decrease in uterine blood flow. The data indicate that in the pregnant sheep and dog the circulatory action of oxytocin is limited to the pregnant uterus in labor and that the decrease in blood flow is probably due to an increase in intramural vascular resistance caused by the contracting myometrium around the uterine arterioles. Submitted on May 5, 1961

Functional role of angiotensin II type 1 and 2 receptors in regulation of uterine blood flow in nonpregnant sheep

2000 ◽  
Vol 278 (2) ◽  
pp. H353-H359 ◽  
Author(s):  
Donna S. Lambers ◽  
Suzanne G. Greenberg ◽  
Kenneth E. Clark
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Angiotensin Ii ◽  
Uterine Artery ◽  
Receptor Subtype ◽  
Ang Ii ◽  
Uterine Blood Flow ◽  
Response Curves ◽  
Vascular Responses

The objective was to determine the receptor subtype of angiotensin II (ANG II) that is responsible for vasoconstriction in the nonpregnant ovine uterine and systemic vasculatures. Seven nonpregnant estrogenized ewes with indwelling uterine artery catheters and flow probes received bolus injections (0.1, 0.3 and 1 μg) of ANG II locally into the uterine artery followed by a systemic infusion of ANG II at 100 ng ⋅ kg−1 ⋅ min−1for 10 min to determine uterine vasoconstrictor responses. Uterine ANG II dose-response curves were repeated following administration of the ANG II type 2 receptor (AT2) antagonist PD-123319 and then repeated again in the presence of an ANG II type 1 receptor (AT1) antagonist L-158809. In a second experiment, designed to investigate the mechanism of ANG II potentiation that occurred in the presence of AT2 blockade, nonestrogenized sheep received a uterine artery infusion of L-158809 (3 mg/min for 5 min) prior to the infusion of 0.03 μg/min of ANG II for 10 min. ANG II produced dose-dependent decreases in uterine blood flow ( P < 0.03), which were potentiated in the presence of the AT2 antagonist ( P < 0.02). Addition of the AT1 antagonist abolished the uterine vascular responses and blocked ANG II-induced increases in systemic arterial pressure ( P < 0.01). Significant uterine vasodilation ( P < 0.01) was noted with AT1 blockade in the second experiment, which was reversed by administration of the AT2 antagonist or by the nitric oxide synthetase inhibitor N ω-nitro-l-arginine methyl ester. We conclude that the AT1- receptors mediate the systemic and uterine vasoconstrictor responses to ANG II in the nonpregnant ewe. AT2-receptor blockade resulted in a potentiation of the uterine vasoconstrictor response to ANG II, suggesting that the AT2-receptor subtype may modulate uterine vascular responses to ANG II potentially by release of nitric oxide.

Fetal placental vascular responses to prostacyclin after angiotensin II-induced vasoconstriction

1989 ◽  
Vol 257 (1) ◽  
pp. E102-E107
Author(s):  
V. M. Parisi ◽  
S. W. Walsh
Keyword(s):  
Blood Flow ◽  
Angiotensin Ii ◽  
Vascular Resistance ◽  
Control Period ◽  
Vena Cava ◽  
Ang Ii ◽  
Flow Measurements ◽  
Control Value ◽  
Blood Flow Measurements ◽  
Infusion Period

The vasodilator prostacyclin is produced by many fetal tissues and may serve to protect umbilical placental blood flow. We hypothesized that prostacyclin could reverse fetoplacental vasoconstriction produced by angiotensin II (ANG II). Studies were done in eight unanesthetized near-term ovine fetuses. After a control period, ANG II was infused into the fetal inferior vena cava at a rate of 0.5 microgram/min for 40 min. Twenty minutes after starting the ANG II infusion, an infusion of prostacyclin at a rate of 5 micrograms/min was added to the ANG II infusion. Blood flows were measured by the radioactive microsphere technique. Blood flow measurements were made during the control period, 20 min after starting the ANG II infusion, and 20 min after adding prostacyclin to the ANG II infusion. ANG II produced significant fetal hypertension and renal, intestinal, and placental vasoconstriction. Placental vascular resistance rose from 0.14 +/- 0.01 to 0.18 +/- 0.01 mmHg.min.kg fetal wt.ml-1 during the ANG II infusion period (P less than 0.05). The addition of prostacyclin to the ANG II infusion resulted in a return to control values for fetal blood pressure and renal and intestinal resistance. However, placental vasoconstriction was not reversed by addition of prostacyclin as placental vascular resistance remained significantly elevated over the control value (0.17 +/- 0.01 mmHg.min.kg fetal wt.ml-1). Although unchanged by ANG II infusion, fetal pH decreased significantly during the ANG II plus prostacyclin infusion period. We conclude that ANG II causes fetal hypertension and renal and intestinal vasoconstriction, which are reversed by prostacyclin.(ABSTRACT TRUNCATED AT 250 WORDS)

Systemic and uterine responses to chronic infusion of estradiol-17 beta

1993 ◽  
Vol 265 (5) ◽  
pp. E690-E698 ◽  
Author(s):  
R. R. Magness ◽  
C. R. Parker ◽  
C. R. Rosenfeld
Keyword(s):  
Heart Rate ◽  
Blood Flow ◽  
Cardiac Output ◽  
Angiotensin Ii ◽  
Mean Arterial Pressure ◽  
Stroke Volume ◽  
Ang Ii ◽  
Uterine Blood Flow ◽  
Pressor Responses ◽  
Chronic Infusion

Human and ovine pregnancies are associated with increases in plasma levels of estrogens and angiotensin II (ANG II), cardiac output (CO), blood volume (BV), and uterine blood flow (UBF), as well as attenuated ANG II pressor responses. We hypothesized that, in nonpregnant animals, prolonged estradiol-17 beta (E2 beta) treatment would reproduce these endocrine and hemodynamic alterations. Nonpregnant ovariectomized ewes (n = 5) received 5 microgram E2 beta/kg iv followed by 220 micrograms/day for 14 days. Plasma E2 beta increased from 36 +/- 6 to 269 +/- 79 (SE) pg/ml (P < 0.05) during E2 beta treatment, returning to control values 4 days posttreatment. By 3 days of E2 beta, mean arterial pressure (MAP) and systemic vascular resistance (SVR) fell 9 +/- 1 and 29 +/- 1%, whereas heart rate (HR) and CO increased 20 +/- 5 and 26 +/- 1% (P < 0.05). Stroke volume (SV), BV, and plasma volume were unchanged until 7 days of E2 beta, with values rising 17 +/- 5, 13 +/- 3, and 14 +/- 4, respectively (P < 0.05). Although MAP remained similarly depressed (-11 +/- 1%) during week 2 of E2 beta, SVR decreased further (-37 +/- 3%) and was associated with additional increases (P < 0.05) in CO to 44 +/- 5%, reflecting rises in SV (21 +/- 2%) but not HR. Increases in BV correlated with rises in CO (r = 0.55) and SV (r = 0.64) but not HR (r = -0.04).(ABSTRACT TRUNCATED AT 250 WORDS)

Fever and regional blood flows in wethers and parturient ewes

1988 ◽  
Vol 65 (1) ◽  
pp. 165-172 ◽  
Author(s):  
C. M. Blatteis ◽  
J. R. Hales ◽  
A. A. Fawcett ◽  
T. A. Mashburn
Keyword(s):  
Blood Flow ◽  
Cardiac Output ◽  
Regional Blood Flow ◽  
Flow Distribution ◽  
Full Term ◽  
Blood Flows ◽  
Pregnant Sheep ◽  
Regional Blood Flows ◽  
Placental Blood ◽  
Placental Blood Flow

To determine whether the reported absence of fever in full-term-pregnant ewes might be associated with shifts of regional blood flows from thermogenic tissues to placenta during this critical period, fevers were induced twice by injections of Escherichia coli lipopolysaccharide (LPS, 0.25 microgram/kg iv) into each of six Merino ewes from 8 to 1 days prepartum, and their regional blood flow distribution was measured with radioactive, 15-microns-diam microspheres before and during the rise in fever (when their rectal temperature had risen approximately 0.4 degree C). Unexpectedly, fever always developed, rising to heights not significantly different at any time before parturition [4-8 days prepartum = 0.81 +/- 0.23 degree C (SE); 1-3 days prepartum = 0.75 +/- 0.17 degree C) and similar to those in three wethers treated similarly (0.90 +/- 0.10 degree C). Generally, during rising fever, blood flow in the ewes shifted away from heat loss tissues (e.g., skin, nose) to heat production tissues (e.g., shivering muscle, fat) and cardiac output increased; blood flow through redistribution organs (e.g., splanchnic bed) decreased. The reverse occurred during defervescence. Utero-placental blood flow remained high in the febrile ewes. These regional blood flow distributions during febrigenesis and lysis are essentially the same as those during exposures to ambient cold and heat, respectively. Some differences in the responses of cardiac output and its redistribution, however, were apparent between wethers and pregnant ewes. We conclude that 1) the previously reported "absence of fever in the full-term-pregnant sheep" should not be regarded as a general phenomenon and 2) full-term-pregnant sheep support fever production without sacrificing placental blood flow.

Combined effects of autoregulation and vasoconstrictors on hindquarters vascular resistance

1990 ◽  
Vol 258 (4) ◽  
pp. H1032-H1041 ◽  
Author(s):  
G. A. Meininger ◽  
J. P. Trzeciakowski
Keyword(s):  
Blood Flow ◽  
Vascular Resistance ◽  
Dose Response ◽  
Perfusion Pressure ◽  
Combined Effects ◽  
Ang Ii ◽  
Response Curves ◽  
Local Pressure ◽  
Pressure Flow ◽  
Dose Dependent

Relative contributions of local autoregulatory tone and vasoconstrictor tone to skeletal muscle vascular resistance were studied in anesthetized rats during hypertension produced by vasoconstrictor infusion. Rats were instrumented with a Doppler flow probe on the sacral aorta (SA) to measure blood flow and to allow calculation of vascular resistance. An occluder was placed on the SA and used to produce stepwise reductions in local perfusion pressure. Pressure-flow curves for the hindquarters were obtained in the absence and presence of elevated mean arterial pressure (MAP) produced by infusion of angiotensin II (ANG II; 50-1,247 ng.kg-1.min-1) or phenylephrine (PE; 2.5-12.4 micrograms.kg-1.min-1). Both ANG II and PE infusion increased MAP. For example, MAP was increased by ANG II from 91 to 134 mmHg and by PE from 89 to 156 mmHg. In addition, infusions of ANG II and PE produced dose-dependent rightward shifts in the hindquarters pressure-flow relationship. To examine the effect of pressure on the dose-response relationships of ANG II or PE, local perfusion pressure was adjusted to remain constant at various pressure levels that were independent of MAP during drug infusions. This produced a series of distinct dose-response curves with each curve defined by a different pressure level and with each characterized by a different maximum change in vascular resistance. If local perfusion pressure was not held constant but was permitted to increase with MAP, a compound dose-response curve was obtained in which the combined effects of the change in local pressure (i.e., autoregulation) and vasoconstrictor dose on vascular resistance could be discerned. These data demonstrate that hindquarters blood flow autoregulation continues to occur in the presence of vasoconstrictors. Consequently, autoregulatory mechanisms may be stimulated by any increase in MAP whether associated with systemic vasoconstrictor infusion or activation of neurohumoral pressor systems. The result is an amplified rise in local vascular resistance.

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