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

1989 ◽  
Vol 257 (6) ◽  
pp. R1457-R1461 ◽  
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.

Metabolic clearance of angiotensin II in pregnant and nonpregnant sheep

1985 ◽  
Vol 249 (1) ◽  
pp. E49-E55 ◽  
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.

Pulmonary vascular reactivity is blunted in pregnant rats

1982 ◽  
Vol 53 (3) ◽  
pp. 703-707 ◽  
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.

NG-monomethyl-L-arginine and nitroarginine potentiate pressor responsiveness of vasoconstrictors in conscious rats

1992 ◽  
Vol 262 (6) ◽  
pp. R1137-R1144 ◽  
Author(s):  
K. P. Conrad ◽  
S. L. Whittemore
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Pressor Response ◽  
Renin Angiotensin System ◽  
Rat Aorta ◽  
Bolus Administration ◽  
Ang Ii ◽  
Baseline Blood Pressure ◽  
Conscious Rats ◽  
Pressor Responses

NG-monomethyl-L-arginine (NMA) and nitroarginine have been reported to be competitive inhibitors of the production of endothelium-derived relaxing factor (EDRF). In chronically instrumented conscious rats, we observed that the pressor response of NMA was attenuated by pretreatment with L-arginine but not by pretreatment with D-arginine, phentolamine, or meclofenamate. Inhibitors of the renin-angiotensin system, captopril and [Sar1,Ile5,Thr8]angiotensin II, did not significantly affect the pressor response of NMA, either. Ten to fifteen minutes after bolus administration of 7-15 mg/kg NMA, when baseline blood pressure was virtually restored, the pressor responses of angiotensin II (ANG II), norepinephrine, and arginine vasopressin were significantly potentiated by approximately 30-40% compared with control values. This potentiation was prevented by pretreatment with L- but not D-arginine. It was also observed in conscious rats subjected to ganglionic blockade. Likewise, the pressor responses of ANG II were significantly increased during infusions of 2 and 5 micrograms/min nitroarginine methyl ester (NAME), dosages that raised baseline blood pressure by 6 +/- 2 and 15 +/- 3 mmHg, respectively. During administration of 5 and 50 micrograms/min NAME, hypotensive responses of methacholine and histamine were only modestly attenuated compared with the responses recorded during infusions of phenylephrine, which raised resting blood pressure to comparable levels. Finally, in freshly isolated rat aorta, NMA inhibited basal and stimulated production of guanosine 3',5'-cyclic monophosphate in a manner comparable to reduced hemoglobin, a known inhibitor of EDRF.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of fast and slow pressor effects of angiotensin II in the conscious rat

1981 ◽  
Vol 241 (3) ◽  
pp. H381-H388 ◽  
Author(s):  
A. J. Brown ◽  
J. Casals-Stenzel ◽  
S. Gofford ◽  
A. F. Lever ◽  
J. J. Morton
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Pressor Response ◽  
Control Period ◽  
Urinary Sodium Excretion ◽  
Sodium Balance ◽  
Pressor Effect ◽  
Ang Ii ◽  
Conscious Rat ◽  
Female Wistar Rats

Female Wistar rats were infused intravenously with 5% dextrose for 3 days, then with angiotensin II (ANG II) in 5% dextrose at 20 ng . kg-1 . min-1 for 7 days, and finally with dextrose for 2.5 days. ANG II raised mean arterial pressure (MAP) gradually; by the 7th day it was 49.7 mmHg higher than during the dextrose control period in the same rats. Control rats were infused with dextrose for 12.5 days; MAP did not change. Plasma ANG II concentration was measured during infusion. In hypertensive rats on the 7th day of ANG II infusion, it was six times higher than in control rats infused with dextrose. Changes of blood pressure and plasma ANG II concentration were compared in further rats infused with much larger doses of ANG II. Rats receiving 270 ng . kg-1 . min-1 for 1 h had an almost maximal direct pressor response, MAP rising 45.3 mmHg and plasma ANG II rising 32-fold compared with controls. Thus, infusion of ANG II at low dose without direct pressor effect gradually raises blood pressure to a level similar to the maximum direct pressor effect produced by larger doses of ANG II. Sodium balance and food and water intakes were also measured and did not change during prolonged infusion of ANG II at 20 ng . kg-1 . min-1. Thus, the slow pressure effect of ANG II develops at a lower and more nearly physiological plasma concentration of the peptide than do the direct pressor effect and the effects on drinking, eating, and urinary sodium excretion.

Abstract P041: Proximal Tubule-specific Deletion Of Angiotensin Ii Type 1a Receptors In The Kidney Lowers Basal Blood Pressure And Attenuates Angiotensin Ii-induced Hypertension By Increasing Glomerular Filtration And The Pressure-natriuresis Response

Hypertension ◽  
2020 ◽  
Vol 76 (Suppl_1) ◽  
Author(s):  
Xiao C Li ◽  
Ana P Leite ◽  
Liang Zhang ◽  
Jia L Zhuo
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Proximal Tubule ◽  
Pressor Response ◽  
Control Group ◽  
Ang Ii ◽  
Induced Hypertension ◽  
Basal Blood Pressure ◽  
Pressure Natriuresis ◽  
Specific Deletion

The present study tested the hypothesis that intratubular angiotensin II (Ang II) and AT 1a receptors in the proximal tubules of the kidney plays an important role in basal blood pressure control and in the development of Ang II-induced hypertension. Mutant mice with proximal tubule-specific deletion of AT 1a receptors in the kidney, PT- Agtr1a -/- , were generated to test the hypothesis. Eight groups (n=7-12 per group) of adult male wild-type (WT) and PT- Agtr1a -/- mice were infused with or without Ang II for 2 weeks (1.5 mg/kg, i.p.). Basal systolic, diastolic, and mean arterial pressures were ~13 ± 3 mmHg lower in PT- Agtr1a -/- than WT mice ( P <0.01). Basal glomerular filtration rate (GFR), as measured using transdermal FITC-sinistrin, was significantly higher in PT- Agtr1a -/- mice (WT: 160.4 ± 7.0 μl/min vs. PT- Agtr1a -/- : 186.0 ± 6.0 μl/min, P <0.05). Basal 24 h urinary Na + excretion (U Na V) was significantly higher in PT- Agtr1a -/- than WT mice ( P <0.01). In response to Ang II infusion, both WT and PT- Agtr1a -/- mice developed hypertension, and the magnitude of the pressor response to Ang II was similar in WT (Δ43 ± 3 mmHg, P <0.01) and PT- Agtr1a -/- mice (Δ39 ± 5 mmHg, P <0.01). However, the absolute blood pressure level was still 16 ± 3 mmHg lower in PT- Agtr1a -/- mice ( P <0.01). Ang II significantly decreased GFR to 132.2 ± 7.0 μl/min in WT mice ( P <0.01), and to 129.4 ± 18.6 μl/min in PT- Agtr1a -/- mice ( P <0.01), respectively. In WT mice, U Na V increased from 139.3 ± 22.3 μmol/24 h in the control group to 196.4 ± 29.6 μmol/24 h in the Ang II-infused group ( P <0.01). In PT- Agtr1a -/- mice, U Na V increased from 172.0 ± 10.2 μmol/24 h in the control group to 264.7 ± 35.4 μmol/24 h in the Ang II-infused group ( P <0.01). The pressor response to Ang II was attenuated, while the natriuretic response was augmented by losartan in WT and PT- Agtr1a -/- mice ( P <0.01). Finally, proximal tubule-specific deletion of AT 1a receptors significantly augmented the pressure-natriuresis response and natriuretic responses to acute saline infusion ( P <0.01) or a 2% high salt diet ( P <0.01). We concluded that deletion of AT 1a receptors selectively in the proximal tubules lowers basal blood pressure and attenuates Ang II-induced hypertension by increasing GFR and promoting the natriuretic response in PT- Agtr1a -/- mice.

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

1984 ◽  
Vol 247 (1) ◽  
pp. H100-H108 ◽  
Author(s):  
M. S. Paller
Keyword(s):  
Angiotensin Ii ◽  
Pressor Response ◽  
Receptor Occupancy ◽  
Vascular Response ◽  
Normal Response ◽  
Pregnant Rats ◽  
Inhibition Of Prostaglandin Synthesis ◽  
Vascular Receptor ◽  
Similar Decrease ◽  
In Pregnancy

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.

Total autonomic blockade eliminates the attenuated pressor response to angiotensin II in pregnant rats

1993 ◽  
Vol 265 (6) ◽  
pp. R1270-R1275
Author(s):  
T. Hines ◽  
M. D. Lindheimer ◽  
W. M. Barron
Keyword(s):  
Angiotensin Ii ◽  
Repeated Measures ◽  
Vascular Reactivity ◽  
Peripheral Resistance ◽  
Systemic Resistance ◽  
Bolus Administration ◽  
Ang Ii ◽  
Pregnant Rats ◽  
Pressor Responses ◽  
Autonomic Blockade

Pressor responses to angiotensin II (ANG II) are markedly attenuated in reflex-intact pregnant animals, a phenomenon widely attributed to intrinsic changes in vascular reactivity. To test the hypothesis that gestational augmentation of neural reflex activity contributes importantly to this phenomenon, changes in mean arterial pressure (MAP), cardiac output (CO), and total peripheral resistance (TPR) were compared during constant infusion (25-400 ng.kg-1.min-1) of ANG II in conscious virgin and pregnant rats, using a model of total autonomic blockade (chlorisondamine chloride and methscopolamine bromide), with restoration of baseline hemodynamics by infusion of norepinephrine. Basal CO was higher and TPR lower in pregnant (CO 121.8 +/- 3.8 ml/min; TPR 0.78 +/- 0.04 mmHg.ml-1.min) compared with virgin (CO 95.9 +/- 3.9 ml/min; TPR 1.05 +/- 0.08 mmHg.ml-1.min) rats (P < 0.005). Pressor responses to ANG II were similar in both groups of reflex-blocked animals due to comparable changes in TPR and CO (not significant by repeated-measures analysis of variance). Other experiments demonstrated that changes in MAP after bolus administration of ANG II did not differ in areflexic virgin and gravid rats. Thus in the absence of autonomic control ANG II has similar effects on systemic resistance in pregnant and nonpregnant rats, suggesting that reflex neural mechanisms contribute significantly to gestational changes in pressor responsiveness. These data further suggest that pregnancy is not accompanied by a generalized decrease in vascular reactivity to all pressor agents.

Evidence that centrally released arginine vasopressin is involved in central pressor action of angiotensin II

1996 ◽  
Vol 270 (1) ◽  
pp. H167-H173 ◽  
Author(s):  
S. Lon ◽  
E. Szczepanska-Sadowska ◽  
M. Szczypaczewska
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Arginine Vasopressin ◽  
Pressor Response ◽  
Cardiovascular Effects ◽  
Pressor Effect ◽  
Ang Ii ◽  
Central Administration ◽  
Hypotensive Action ◽  
Series Of Experiments

Five series of experiments were performed on conscious trained dogs to find out whether intracranially released arginine vasopressin (AVP) is involved in mediation of central cardiovascular effects of angiotensin II (ANG II). The dogs were implanted with guide tubes leading to the third cerebral ventricle (ICV) and implanted with the intra-arterial catheters. Blood pressure and heart rate were continuously monitored during intracerebroventricular administration of 1) ANG II alone (250 ng), 2) AVP alone (0.01 ng/min during 10 min), 3) ANG II together with AVP, 4) AVP together with AVP V1-receptor antagonist 1(1-mercapto-4-methylcyclohexaneacetic acid)-8-AVP [MeCAAVP, V1ANT,100 ng/min], and 5) ANG II together with V1ANT. The results revealed that 1) ANG II and AVP applied separately elicited significant, long-lasting increases of blood pressure; 2) the maximum pressor effect after ANG II and AVP applied together did not differ from that after separate application of either of these peptides, but the duration of the pressor response was significantly shorter; 3) pretreatment with V1ANT effectively prevented blood pressure increases elicited by central administration of AVP and ANG II; and 4) after blockade of V1 receptors administration of AVP resulted in a significantly delayed decrease of blood pressure below baseline. The results strongly suggest that 1) centrally released AVP mediates the pressor effect of intracerebroventricularly applied ANG II by means of V1 receptors; 2) intracerebroventricularly applied ANG II and AVP interact to activate the mechanism involved in extinction of their pressor effect; and 3) blockade of central V1 receptors uncovers the hypotensive action of centrally applied AVP.

scholarly journals Genetic and genomic evidence for an important role of the Na+/H+ exchanger 3 in blood pressure regulation and angiotensin II-induced hypertension

2019 ◽  
Vol 51 (4) ◽  
pp. 97-108 ◽  
Author(s):  
Xiao C. Li ◽  
Xiaowen Zheng ◽  
Xu Chen ◽  
Chunling Zhao ◽  
Dongmin Zhu ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Proximal Tubule ◽  
Proximal Tubules ◽  
Ang Ii ◽  
Pressure Regulation ◽  
Blood Pressure Homeostasis ◽  
Induced Hypertension ◽  
Basal Blood Pressure

The sodium (Na+)/hydrogen (H+) exchanger 3 (NHE3) and sodium-potassium adenosine triphosphatase (Na+/K+-ATPase) are two of the most important Na+ transporters in the proximal tubules of the kidney. On the apical membrane side, NHE3 primarily mediates the entry of Na+ into and the exit of H+ from the proximal tubules, directly and indirectly being responsible for reabsorbing ~50% of filtered Na+ in the proximal tubules of the kidney. On the basolateral membrane side, Na+/K+-ATPase serves as a powerful engine driving Na+ out of, while pumping K+ into the proximal tubules against their concentration gradients. While the roles of NHE3 and Na+/K+-ATPase in proximal tubular Na+ transport under in vitro conditions are well recognized, their respective contributions to the basal blood pressure regulation and angiotensin II (ANG II)-induced hypertension remain poorly understood. Recently, we have been fortunate to be able to use genetically modified mouse models with global, kidney- or proximal tubule-specific deletion of NHE3 to directly determine the cause and effect relationship between NHE3, basal blood pressure homeostasis, and ANG II-induced hypertension at the whole body, kidney and/or proximal tubule levels. The purpose of this article is to review the genetic and genomic evidence for an important role of NHE3 with a focus in the regulation of basal blood pressure and ANG II-induced hypertension, as we learned from studies using global, kidney- or proximal tubule-specific NHE3 knockout mice. We hypothesize that NHE3 in the proximal tubules is necessary for maintaining basal blood pressure homeostasis and the development of ANG II-induced hypertension.

Effect of sinoaortic denervation on pressor responses in pregnant rats

1992 ◽  
Vol 262 (6) ◽  
pp. R1100-R1105 ◽  
Author(s):  
T. Hines ◽  
W. M. Barron
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Angiotensin Ii ◽  
Mean Arterial Pressure ◽  
Arterial Baroreflex ◽  
Pregnant Rats ◽  
Pregnant Rat ◽  
Sham Surgery ◽  
Pressor Responses ◽  
Vascular Sensitivity

We tested the hypothesis that augmented arterial baroreflex activity contributes to attenuation of pressor responses in intact pregnant animals by comparing changes in blood pressure and heart rate during infusions of angiotensin II, phenylephrine, and vasopressin in chronically instrumented pregnant and virgin rats approximately 5 wk after sinoaortic denervation (SAD) or sham surgery. Baseline mean arterial pressure was significantly lower in pregnant animals in both the sham-operated (pregnant 91.7 +/- 1.7 mmHg, virgin 103.7 +/- 2.5 mmHg) and SAD states (pregnant 107.3 +/- 4.0 mmHg, virgin 114.1 +/- 4.0 mmHg). Pressor responses to all three agents were significantly blunted in pregnant animals compared with similarly treated virgins, with the magnitude of attenuation similar in both sham and SAD states. Heart rate decreased similarly in reflex-intact pregnant and virgin animals during pressor infusions. These findings suggest that attenuated pressor responses in the pregnant rat are due primarily to mechanisms other than augmentation of arterial baroreflex activity and are consistent with a generalized reduction in vascular sensitivity during gestation.

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