Mechanism of decreased pressor responsiveness to ANG II, NE, and vasopressin in pregnant rats

The mechanism of decreased pressor responsiveness to pressor agents was examined serially throughout pregnancy in conscious rats. Rats, 15 and 20 days pregnant, showed marked blunting of the pressor response to graded doses of angiotensin, whereas after only 5 days of pregnancy there was a normal response and at 10 days an intermediate pressor response. A role for prior occupancy of vascular angiotensin II receptors for the blunted pressor response was made less likely by the observation that treatment with captopril to decrease endogenous angiotensin II did not improve the angiotensin II pressor response in 15-day pregnant rats. Studies of smooth muscle receptor binding of angiotensin II showed that, in pregnancy, receptor affinity and number was not changed. Inhibition of prostaglandin synthesis with meclofenamate increased the pressor response to angiotensin II toward normal in pregnant animals. The blunted vascular response in pregnancy was not specific for angiotensin since pregnant animals showed a similar decrease in the response to both norepinephrine and arginine vasopressin. Furthermore, meclofenamate increased the pressor response to norepinephrine and vasopressin in pregnant rats. We conclude that pressor hyporesponsiveness in pregnancy is not specific for angiotensin II and is not caused by alterations in vascular receptor occupancy or binding. In pregnancy there is a decreased pressor response to all three major pressor agents that is improved by inhibition of prostaglandin production.

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Pulmonary vascular reactivity is blunted in pregnant rats

Journal of Applied Physiology ◽

10.1152/jappl.1982.53.3.703 ◽

1982 ◽

Vol 53 (3) ◽

pp. 703-707 ◽

Cited By ~ 15

Author(s):

K. I. Fuchs ◽

L. G. Moore ◽

S. Rounds

Keyword(s):

Angiotensin Ii ◽

Vascular Reactivity ◽

Pulmonary Arterial Pressure ◽

Pressor Response ◽

Female Rats ◽

Pregnant Rats ◽

Constant Flow Rate ◽

Pressor Responses ◽

Pulmonary Arterial ◽

In Pregnancy

Pulmonary arterial pressure is decreased in pregnant women despite increased cardiac output, suggesting that pulmonary vascular resistance is decreased in pregnancy. To determine if pulmonary vascular reactivity is decreased in pregnant rats, lungs isolated from pregnant rats were perfused with blood from other pregnant rats at constant flow rate, and pressor responses to airway hypoxia and to angiotensin II were measured. Compared with responses obtained in lungs from nonpregnant female rats, hypoxic and angiotensin II pressor responses were blunted in pregnancy. To separate possible effects of pregnancy on the lung from those of substance(s) circulating in the blood in pregnancy, we perfused lungs from nonpregnant rats with blood from pregnant rats. Both the hypoxic and angiotensin II pressor responses were blunted by blood from pregnant rats. The angiotensin II pressor response was blunted also in lungs from pregnant rats perfused with blood from nonpregnant rats. These results suggest that a circulating substance is responsible for blunting of pulmonary vascular reactivity in pregnancy and that changes in the lung induced by pregnancy also depress angiotensin II responses. It is unlikely that estrogen and progesterone were responsible for these effects, since lungs and blood obtained from animals treated with these hormones did not have blunted pulmonary vascular reactivity.

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Role for central angiotensin II in control of blood pressure during pregnancy

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1989.257.6.r1457 ◽

1989 ◽

Vol 257 (6) ◽

pp. R1457-R1461 ◽

Cited By ~ 4

Author(s):

T. Hines ◽

J. P. Porter

Keyword(s):

Blood Pressure ◽

Angiotensin Ii ◽

Pressor Response ◽

Sympathetic Ganglia ◽

Ang Ii ◽

Pressure Regulation ◽

Guide Cannula ◽

Pregnant Rats ◽

Pressor Responses ◽

In Pregnancy

It is known that the pressor response to intravenous angiotensin II (ANG II) is blunted in pregnancy. In the present study we examined the pressor response to intracerebroventricular ANG II to determine whether central ANG II effects are also attenuated in conscious pregnant rats. Two to three days before experimentation, animals were instrumented with arterial and venous catheters and a ventricular guide cannula. Pressor responses to 10, 50, and 100 ng iv of ANG II, and 30, 100, and 300 ng iv of norepinephrine were significantly reduced in pregnant animals. The pressor response to 5, 20, and 50 ng iv of vasopressin was not attenuated in pregnant rats. The pressor response to intracerebroventricular 100 ng ANG II was significantly increased in pregnancy. Blockade of the vasopressin V1 receptor and the sympathetic ganglia indicated that the greater pressor response to intracerebroventricular ANG II in pregnancy may be the result of a larger contribution by the sympathetic nervous system. We conclude that the central effects of ANG II are augmented in pregnancy, suggesting a significant role for central ANG II in blood pressure regulation.

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Metabolic clearance of angiotensin II in pregnant and nonpregnant sheep

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1985.249.1.e49 ◽

1985 ◽

Vol 249 (1) ◽

pp. E49-E55 ◽

Cited By ~ 8

Author(s):

R. P. Naden ◽

S. Coultrup ◽

B. S. Arant ◽

C. R. Rosenfeld

Keyword(s):

Angiotensin Ii ◽

Pressor Response ◽

Plasma Concentrations ◽

Metabolic Clearance ◽

Ang Ii ◽

Pressor Responses ◽

Pregnant Sheep ◽

Vascular Responsiveness ◽

Arterial Plasma ◽

In Pregnancy

Reduced vascular responsiveness to infused angiotensin II (ANG II) has been observed during pregnancy. It has been proposed that infusions produce lower circulating concentrations of ANG II in pregnancy, due to an increase in the metabolic clearance rate of ANG II (MCRangii). We have evaluated the MCRangii and the arterial plasma concentrations of ANG II during constant infusions of 1.15 micrograms ANG II/min into chronically instrumented pregnant (n = 6) and nonpregnant (n = 9) sheep. Although the pressor responses were significantly less in the pregnant than in the nonpregnant sheep (17.5 +/- 0.5 vs. 34.9 +/- 3.2 mmHg, P less than 0.001), the values for MCRangii were not different: 56.2 +/- 6.3 ml X min-1 X kg-1 in nonpregnant and 55.9 +/- 4.3 ml X min-1 X kg-1 in pregnant sheep. The steady-state plasma ANG II concentrations during the infusions were slightly less in pregnant than in nonpregnant sheep (388 +/- 36 vs. 454 +/- 36 pg/ml); however, this difference would be responsible for only a 2-mmHg reduction in the pressor response. We conclude that the reduced pressor response to infused ANG II in pregnancy is not due to an increase in MCRangii nor to lower plasma ANG II concentrations.

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Pressor Responsiveness to Angiotensin in Renovascular and Steroid Hypertension

Clinical Science ◽

10.1042/cs057047s ◽

1979 ◽

Vol 57 (s5) ◽

pp. 47s-50s ◽

Cited By ~ 3

Author(s):

E. S. Marks ◽

H. Thurston ◽

R. F. Bing ◽

J. D. Swales

Keyword(s):

Angiotensin Ii ◽

Pressor Response ◽

Plasma Renin ◽

Receptor Occupancy ◽

Bilateral Nephrectomy ◽

Hypertensive Rats ◽

Response Curves ◽

Pressor Responses ◽

Salt Hypertension ◽

Converting Enzyme Inhibition

1. The pressor response to angiotensin II was reduced in rats with early (<6 weeks) and chronic (>4 months) Goldblatt two-kidney, one-clip hypertension and enhanced in DOCA—salt hypertension. 2. Converting enzyme inhibition with captopril brought the angiotensin pressor response curves into closer proximity although the DOCA hypertensive rats were minimally hyper-responsive and rats with early and chronic renovascular hypertension showed slightly reduced responsiveness. 3. After bilateral nephrectomy the pressor responses to angiotensin were similar. 4. The pressor response to angiotensin II in these animals was inversely related to plasma renin concentration and therefore largely dependent upon receptor occupancy by endogenous angiotensin II. There is no evidence for enhanced pressor responsiveness to angiotensin in either renovascular or DOCA hypertension.

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Dietary protein increases plasma renin and reduces pressor reactivity to angiotensin II

AJP Renal Physiology ◽

10.1152/ajprenal.1986.251.1.f34 ◽

1986 ◽

Vol 251 (1) ◽

pp. F34-F39 ◽

Cited By ~ 5

Author(s):

M. S. Paller ◽

T. H. Hostetter

Keyword(s):

Angiotensin Ii ◽

Dietary Protein ◽

Pressor Response ◽

Renin Angiotensin System ◽

Chronic Administration ◽

Plasma Renin ◽

Prostaglandin Synthesis ◽

Plasma Aldosterone ◽

Ang Ii ◽

Inhibition Of Prostaglandin Synthesis

The effect of dietary protein on the renin-angiotensin system was studied in rats. Rats were fed isocaloric, 50% (high protein, HP), or 6% (low protein, LP) protein diets with identical electrolyte content for 10 days. Food intake and electrolyte excretion were equivalent on the two diets. Plasma renin activity (PRA) was higher in HP (10.0 +/- 2.5 vs. 3.5 +/- 0.5 ng ANG I . ml-1 . h-1, P less than 0.02) as was plasma aldosterone. However, in conscious rats mean arterial pressure (MAP) was not different between groups. The pressor response to graded doses of angiotensin II (ANG II) was diminished by 30-60% with HP (all doses, P less than 0.05). ANG II binding by mesenteric artery smooth muscle particles did not differ between HP and LP. Chronic administration of captopril did not normalize the pressor response in HP. Urinary prostaglandin (PG) E and 6-keto-PGF1 alpha excretion was markedly increased by the HP diet. Acute inhibition of prostaglandin synthesis with meclofenamate restored the pressor response to ANG II in HP to that in LP. In summary, a HP diet increased PRA, plasma aldosterone, urinary PGE, and 6-keto-PGF1 alpha and decreased pressor responsiveness to ANG II. Resistance to ANG II was not reversed by chronic converting enzyme inhibition but was abolished by inhibition of prostaglandin synthesis.

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Pressor responsiveness in pseudopregnant and pregnant rats: role of maternal factors

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1989.257.4.r866 ◽

1989 ◽

Vol 257 (4) ◽

pp. R866-R871 ◽

Cited By ~ 2

Author(s):

M. S. Paller ◽

G. Gregorini ◽

T. F. Ferris

Keyword(s):

Vascular Reactivity ◽

Pressor Response ◽

Ang Ii ◽

Maternal Factors ◽

Synthesis Inhibitor ◽

Pregnant Rats ◽

Plasma Progesterone ◽

Early Increase ◽

In Pregnancy

During pregnancy the pressor response to vasoconstrictor substances such as angiotensin II (ANG II) is diminished, and renal, uterine, and vascular prostaglandin (PG) production may increase. However, little is known about the factors that alter vascular reactivity or stimulate PG synthesis during pregnancy. To ascertain whether these factors are of maternal or fetal-placental origin, we studied vascular reactivity and urinary PGE excretion in pseudopregnant rats. Pseudopregnant rats had plasma progesterone and weight gain similar to that observed in pregnant rats. Urinary PG excretion in nonpregnant rats was approximately 70 ng/24 h and remained constant during a 12-day observation. In contrast, urinary PG excretion in both pregnant and in pseudopregnant rats rose to levels approximately twice control within 4-6 days. The pressor response to ANG II was diminished in pseudopregnant rats compared with nonpregnant rats. When the PG synthesis inhibitor meclofenamate was given there was no change in the pressor response to ANG II in nonpregnant animals, but in pseudopregnant animals meclofenamate produced a significant increase in the pressor response to ANG II. The pressor response to norepinephrine and arginine vasopressin (AVP) was not diminished in pseudopregnant animals, and meclofenamate did not increase the pressor response to these agents. Therefore, a developing fetus and placenta is not necessary for the decrease in pressor response to ANG II nor for the early increase in urinary PGE excretion. Like in pregnancy, the pressor response to ANG II was increased after meclofenamate in pseudopregnancy. Increased PG production may, therefore, be partly responsible for the decrease in pressor responsiveness to ANG II. However, pseudopregnancy, unlike pregnancy, did not affect pressor responsiveness to norepinephrine or AVP. Both maternal and fetal-placental factors seem required for the reduction in responsiveness to norepinephrine and AVP in pregnancy.

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Comparative study of pressor and heart rate responses to angiotensin II and noradrenaline in pregnant and non-pregnant women

Clinical Science ◽

10.1042/cs0820157 ◽

1992 ◽

Vol 82 (2) ◽

pp. 157-162 ◽

Cited By ~ 19

Author(s):

Margaret Ramsay ◽

Fiona Broughton Pipkin ◽

Peter Rubin

Keyword(s):

Blood Pressure ◽

Heart Rate ◽

Angiotensin Ii ◽

Pregnant Women ◽

Arterial Blood Pressure ◽

Vascular Reactivity ◽

Pressor Response ◽

Arterial Blood ◽

Diastolic Arterial Blood Pressure ◽

In Pregnancy

1. Twenty-eight healthy non-pregnant women and 28 women in the first or second trimester of pregnancy were studied. They were given an incremental intravenous infusion of either noradrenaline or angiotensin II. Pressor and heart rate responses were documented. 2. Dose-pressor response curves were constructed for the two agents in pregnant and non-pregnant women (n=14 in each group). The regression parameters of slope and intercept were calculated, and were used to derive the variables of dose required to elicit a 10 mmHg rise in systolic or diastolic blood pressure. 3. The pressor response to angiotensin II was diminished in pregnancy, with approximately twice the dose being required to raise the systolic or diastolic arterial blood pressure as in non-pregnant subjects. 4. The systolic pressor response to noradrenaline was slightly diminished in pregnancy, but the diastolic pressor response was unchanged. There were no significant differences between the doses of noradrenaline required to elicit a 10 mmHg rise in systolic or diastolic arterial blood pressure in pregnant or non-pregnant subjects. 5. There was a diminution in the bradycardia evoked in response to both hormones in pregnancy. 6. We conclude that the well-documented pressor insensitivity to angiotensin II during pregnancy is a specific phenomenon, not a manifestation of a generalized reduction in vascular reactivity.

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