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.

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.

Effects of indomethacin, during pregnancy in the rat, on responses to noradrenaline and angiotensin II in vivo, and responses to phenylephrine in vitro

1990 ◽  
Vol 2 (5) ◽  
pp. 587 ◽  
Author(s):  
C Jansakul ◽  
RG King ◽  
AL Boura
Keyword(s):  
Body Weight ◽  
Angiotensin Ii ◽  
Plasma Volume ◽  
Ang Ii ◽  
Pregnant Rats ◽  
Prostaglandin Production ◽  
Pressor Responses

Pressor responses to both angiotensin II (Ang II) and noradrenaline (NA) were reduced in 20-day-pregnant rats compared with those in non-pregnant animals, regardless of whether the results were expressed in terms of the dose per kilogram of body weight or per millilitre of estimated plasma volume. Inhibition of prostaglandin production with indomethacin (10 mg kg-1, i.v.) was not accompanied by any significant effect on responses to Ang II in either non-pregnant or 20-day-pregnant animals. However, it attenuated the effects of NA in 20-day-pregnant rats. Indomethacin (10(-5) or 3 x 10(-5) M) did not potentiate in vitro vasoconstrictor responses to phenylephrine of endothelium-intact or -denuded thoracic aortic rings from non-pregnant or 20-day-pregnant rats. These results suggest that subsensitivity to Ang II or NA during pregnancy in the rat is not due to dilution of the dose of these autacoids resulting from increased plasma volume, nor to an increased output of vasodilator prostaglandins.

Vascular reactivity during the development of two-kidney, one-clip Goldblatt hypertension in conscious dogs

1982 ◽  
Vol 60 (12) ◽  
pp. 1482-1492 ◽  
Author(s):  
Stan Greenberg ◽  
Claude McGowan ◽  
Monica Gaida
Keyword(s):  
Vascular Reactivity ◽  
Peripheral Resistance ◽  
Vascular Wall ◽  
Conscious Dogs ◽  
Ang Ii ◽  
Intrinsic Factors ◽  
Pressor Responses ◽  
Pressure Changes ◽  
Goldblatt Hypertension

This study evaluates the sequential changes in vascular reactivity in conscious dogs during the early and late phases of two-kidney, one-clip Goldblatt hypertension (2-KGH) produced by unilateral renal artery constriction (URAC). The in vivo responses to serotonin (5-HT), norepinephrine (NE), angiotensin II (Ang II), prostacyclin (PGI2), acetylcholine (ACH), and nitroglycerin (GTN) were reproducible and stable throughout the 32-day period of study in dogs subjected to sham URAC. The vascular responses to 5-HT, Ang II, and PGI2 were enhanced day 1 post-URAC, before mean arterial pressure (MAP), cardiac output (CO), or total peripheral resistance (TPR) increased. The magnitude of the enhanced reactivity progressed on days 4 and 32 post-URAC, as hypertension developed. The pressor responses to NE did not change from pre-URAC values until CO and MAP were elevated. The vasodepressor responses to ACH and GTN diminished over a 12-day period post-URAC, in parallel with the change in CO, but prior to any increase in TPR. These data suggest that in dogs with 2-KGH changes in vascular reactivity precede the development of the increased MAP and TPR of hypertension. The lack of uniformity of the onset of the reactivity changes to the different agonists suggests that both intrinsic factors and pressure changes modify the vascular wall in the early and later stages of 2-KGH.

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)

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.

scholarly journals Analysis of responses to angiotensin II in the mouse

2001 ◽  
Vol 2 (1_suppl) ◽  
pp. S48-S53 ◽  
Author(s):  
Trinity J Bivalacqua ◽  
Hunter C Champion ◽  
Albert L Hyman ◽  
Dennis B McNamara ◽  
Philip J Kadowitz
Keyword(s):  
Angiotensin Ii ◽  
Response Curve ◽  
Peripheral Resistance ◽  
Systemic Arterial Pressure ◽  
Ang Ii ◽  
Inhibitory Effects ◽  
Pressor Responses ◽  
Cd1 Mice ◽  
Sympathetic Nervous ◽  
The Right

Responses to angiotensin II (Ang II) were investigated in anaesthetised CD1 mice. Injections of Ang II caused dose-related increases in systemic arterial pressure that were antagonised by candesartan. Responses to Ang II were not altered by PD 123319. At the lowest dose studied (20 µg/kg i.v.), the inhibitory effects of candesartan were competitive, whereas at the highest dose (100 µg/kg i.v.), the dose-response curve for Ang II was shifted to the right in a non-parallel manner. The inhibitory effects of candesartan were selective and were similar in animals pretreated with enalaprilat to reduce endogenous Ang II production. Pressor responses to Ang II were not altered by propranolol, phentolamine or atropine, but were enhanced by hexamethonium. Increases in total peripheral resistance were inhibited by the AT1-receptor antagonist (ARB) but were not altered by AT2-receptor, alpha- or beta-receptor antagonists. These results suggest that pressor responses to Ang II are mediated by AT 1-receptors, are buffered by the baroreceptors, are not modulated by effects on AT2receptors, and that activation of the sympathetic nervous system plays little role in mediating rapid haemodynamic responses to the peptide in anaesthetised mice.

Abstract MP03: ROCK2 Specific Inhibition Attenuates Angiotensin II-induced Hypertension In Mice

Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Daniel J Fehrenbach ◽  
Meena S Madhur
Keyword(s):  
Blood Pressure ◽  
T Cell ◽  
Angiotensin Ii ◽  
Repeated Measures ◽  
Flow Cytometric Analysis ◽  
Coiled Coil ◽  
Ang Ii ◽  
Induced Hypertension

Hypertension, or an elevated blood pressure, is the primary modifiable risk factor for cardiovascular disease, the number one cause of mortality worldwide. We previously demonstrated that Th17 activation and interleukin 17A (IL-17A)/IL-21 production is integral for the full development of a hypertensive phenotype as well as the renal and vascular damage associated with hypertension. Rho-associated coiled-coil containing protein Kinase 2 (ROCK2) serves as a molecular switch upregulating Th17 and inhibiting regulatory T cell (Treg) differentiation. We hypothesize that hypertension is characterized by excessive T cell ROCK2 activation leading to increased Th17/Treg ratios and ultimately end-organ damage. We first showed in vitro that KD025, an experimental orally bioavailable ROCK2 inhibitor inhibits Th17 cell proliferation and IL-17A/IL-21 production. To determine if hypertensive stimuli such as endothelial stretch increases T cell ROCK2 expression, we cultured human aortic endothelial cells exposed to 5% (normotensive) or 10% (hypertensive) stretch with circulating human T cells and HLA-DR+ antigen presenting cells. Hypertensive stretch increased T cell ROCK2 expression 2-fold. We then tested the effect of ROCK2 inhibition with KD025 (50mg/kg i.p. daily) in vivo on angiotensin II (Ang II)-induced hypertension. Treatment with KD025 significantly attenuated the hypertensive response within 1 week of Ang II treatment (systolic blood pressure: 139± 8 vs 108±7mmHg) and this persisted for the duration of the 4 week study reaching blood pressures 20 mmHg lower (135±13mmHg) than vehicle treated mice (158±4mmHg p<0.05 effect of treatment 2-way Repeated Measures ANOVA). Flow cytometric analysis of tissue infiltrating leukocytes revealed that KD025 treatment increased Treg/Th17 ratios in the kidney (0.61±0.03 vs 0.79±0.08, p<0.05 student’s t-test). Thus, T cell ROCK2 may be a novel therapeutic target for the treatment of hypertension.

Enhanced vasodilation to acetylcholine in athletes is associated with lower plasma cholesterol

1996 ◽  
Vol 270 (6) ◽  
pp. H2008-H2013 ◽  
Author(s):  
B. A. Kingwell ◽  
B. Tran ◽  
J. D. Cameron ◽  
G. L. Jennings ◽  
A. M. Dart
Keyword(s):  
Sodium Nitroprusside ◽  
Vascular Resistance ◽  
Repeated Measures ◽  
Vascular Reactivity ◽  
Plasma Cholesterol ◽  
Total Cholesterol Level ◽  
Venous Occlusion ◽  
Ang Ii ◽  
Elevated Cholesterol ◽  
Forearm Vascular Resistance

We investigated a change in vascular reactivity as a potential adaptive mechanism to chronic exercise. The study consisted of 2 separate protocols with 10 male athletes and 10 age-matched sedentary male control subjects participating in each. Protocol 1 investigated forearm blood flow responses to intra-arterial infusions of acetylcholine and sodium nitroprusside by use of venous occlusion plethysmography. Protocol 2 used identical techniques to study responses to norepinephrine, angiotensin II (ANG II), and NG-monomethyl-L-arginine (L-NMMA). The percent reduction in forearm vascular resistance to acetylcholine was significantly greater in the athletic compared with the sedentary group (multivariate analysis of variance for repeated measures, P = 0.03). Covariance analysis suggested that the lower total cholesterol level of the athletic group (P = 0.03) may contribute to their enhanced responsiveness to acetylcholine. There were no differences between athletic and sedentary groups in the forearm vascular resistance responses to norepinephrine, ANG II, sodium nitroprusside, or L-NMMA. These data support the hypothesis that long-term endurance training is associated with enhanced endothelium-dependent dilator reserve due to altered lipoprotein levels in athletes. This finding may have therapeutic application in conditions of elevated cholesterol and impaired vasodilator capacity including hypertension, hypercholesterolemia, atherosclerosis, and cardiac failure.

Angiotensin II induces insulin resistance independent of changes in interstitial insulin

1999 ◽  
Vol 277 (5) ◽  
pp. E920-E926 ◽  
Author(s):  
Joyce M. Richey ◽  
Marilyn Ader ◽  
Donna Moore ◽  
Richard N. Bergman
Keyword(s):  
Insulin Resistance ◽  
Heart Rate ◽  
Blood Flow ◽  
Angiotensin Ii ◽  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Glucose Uptake ◽  
Peripheral Resistance ◽  
Glucose Turnover ◽  
Ang Ii

We set out to examine whether angiotensin-driven hypertension can alter insulin action and whether these changes are reflected as changes in interstitial insulin (the signal to which insulin-sensitive cells respond to increase glucose uptake). To this end, we measured hemodynamic parameters, glucose turnover, and insulin dynamics in both plasma and interstitial fluid (lymph) during hyperinsulinemic euglycemic clamps in anesthetized dogs, with or without simultaneous infusions of angiotensin II (ANG II). Hyperinsulinemia per se failed to alter mean arterial pressure, heart rate, or femoral blood flow. ANG II infusion resulted in increased mean arterial pressure (68 ± 16 to 94 ± 14 mmHg, P < 0.001) with a compensatory decrease in heart rate (110 ± 7 vs. 86 ± 4 mmHg, P < 0.05). Peripheral resistance was significantly increased by ANG II from 0.434 to 0.507 mmHg ⋅ ml−1⋅ min ( P < 0.05). ANG II infusion increased femoral artery blood flow (176 ± 4 to 187 ± 5 ml/min, P < 0.05) and resulted in additional increases in both plasma and lymph insulin (93 ± 20 to 122 ± 13 μU/ml and 30 ± 4 to 45 ± 8 μU/ml, P < 0.05). However, glucose uptake was not significantly altered and actually had a tendency to be lower (5.9 ± 1.2 vs. 5.4 ± 0.7 mg ⋅ kg−1⋅ min−1, P > 0.10). Mimicking of the ANG II-induced hyperinsulinemia resulted in an additional increase in glucose uptake. These data imply that ANG II induces insulin resistance by an effect independent of a reduction in interstitial insulin.

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.

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