The effect of prostaglandin E1 upon the pressor and hormonal response to exogenous angiotensin II in human pregnancy

1987 ◽  
Vol 72 (3) ◽  
pp. 351-357 ◽  
Author(s):  
F. Broughton Pipkin ◽  
R. Morrison ◽  
P. M. S. O'Brien

1. The effect of prostaglandin E1 (PGE1) on the pressor and hormonal response to angiotensin (ANG) II has been studied in 22 women in second trimester pregnancy. Three-point dose–response curves were initially determined for all women. Eleven then received an infusion of PGE1 while the remainder received an infusion of normal saline as controls. The dose–response curves to ANG II were re-studied after a period of stabilization. 2. Although assignation to treatment group was random, differences were found in age and basal blood pressure between the control group and those given PGE1. The pressor data from the PGE1 group were thus split by age for analysis. 3. The administration of ANG II alone was associated with significant (P<0.001 at all doses) pressor effects without accompanying bradycardia. Plasma renin concentration (PRC) was suppressed (P<0.001). Plasma aldosterone concentration rose (P<0.001), the magnitude of the rise being directly associated with the plasma ANG II concentrations achieved (P<0.05). 4. The infusion of PGE, had no significant effect on basal blood pressure, but evoked a sustained tachycardia in both age groups (P<0.001). Basal hormone concentrations were unchanged. 5. The pressor response to ANG II was blunted in the presence of PGE1, in both age groups, the overall effect being greatest when the initial response had been large (P<0.05). Measured plasma concentrations of ANG II were lower under these circumstances (P<0.02). PRC fell (P<0.05 for both groups) and plasma aldosterone concentrations rose (P<0.005 for the treated and P<0.001 for the control groups), but the magnitude of these changes did not differ significantly in the two groups. 6. These data support the hypothesis of a for the vasodilator prostaglandins in minimizing the potential pressor effects of the raised ANG II concentrations seen in pregnancy.

1982 ◽  
Vol 62 (4) ◽  
pp. 373-380 ◽  
Author(s):  
M. G. Nicholls ◽  
M. Tree ◽  
J. H. Livesey ◽  
R. Fraser ◽  
J. J. Morton ◽  
...  

1. Potassium was infused intravenously in an incremental fashion and the plasma aldosterone responses were measured in conscious beagle dogs at five different intakes of dietary sodium. 2. Potassium/aldosterone dose—response curves were constructed for each dietary sodium regimen. 3. The rate of increase of plasma potassium during graded potassium infusion became progressively greater with increasing sodium depletion. 4. Regression lines of plasma aldosterone on plasma potassium were progressively elevated and steepened with increasing sodium depletion. 5. The alteration of these dose-response curves could in part have been the result of chronic elevation of plasma potassium and angiotensin II, and depression of plasma sodium, with sodium deprivation. 6. By contrast, acute changes in plasma angiotensin II or sodium concentrations across incremental infusions of potassium did not explain the progressive changes in the potassium/aldosterone dose—response curves. 7. The steepest part of the plasma aldosterone response curve was in the plasma potassium range 4–6 mmol/l. 8. Maximum achieved aldosterone levels were similar to or greater than those attained during angiotensin II infusion in previous studies in beagle dogs. 9. Potassium, like angiotensin II and adrenocorticotropic hormone, becomes a more effective stimulus to aldosterone with sodium depletion, thereby facilitating the preservation of sodium homoeostasis.


1990 ◽  
Vol 258 (3) ◽  
pp. F741-F750 ◽  
Author(s):  
B. H. Yuan ◽  
J. B. Robinette ◽  
J. D. Conger

Differential sensitivity of the pre- and postglomerular arterial vessels to vasoconstrictor activity of angiotensin II (ANG II) and norepinephrine (NE) is controversial. To avoid the complex extravascular neurohumoral variables that may have accounted for different results in the intact rat kidney, an isolated arteriole technique was used to examine the dose responses of ANG II and NE on afferent (AA) and efferent arterioles (EA) from Sprague-Dawley rats. EA were more sensitive than AA to ANG II (EC50 = 3.2 +/- 1.8 x 10(-11) and 1.0 +/- 1.6 x 10(-9) M, respectively, P less than 0.001), whereas EC50 of both AA and EA to NE were similar (3.4 +/- 2.3 x 10(-8) and 1.4 +/- 2.6 x 10(-8) M, respectively). The dose-response curves of AA to ANG II were not different when perfused at different luminal pressures (90 and 30 mmHg). In contrast, EA were more sensitive to ANG II at 30 than at 90 mmHg (3.0 +/- 1.2 x 10(-11) and 5.0 +/- 1.8 x 10(-10) M, respectively, P less than 0.005). The EC50 of EA to NE was unaffected by similar changes in luminal pressures. The mean dose-response curves of AA to ANG II were the same with and without the addition of 10(-5) M indomethacin; however, in arterioles displaying a focal constriction pattern to ANG II the response became uniform. It is concluded that, in the isolated rat glomerular arterioles, EA are more sensitive to ANG II than AA, but both vessels respond similarly to NE. The decreased ANG II sensitivity in AA is not related to the higher in vivo pressure, and the attenuated response in AA does not appear to be mediated primarily through ANG II-stimulated vasodilator prostanoid activity. EA sensitivity to ANG II appears to be inversely related to lumen pressure.


1976 ◽  
Vol 51 (s3) ◽  
pp. 151s-153s ◽  
Author(s):  
G. W. Boyd

1. In an investigation of the prolonged pressor response to renin that develops after nephrectomy, angiotensin I dose—response curves and rat renin clearances were studied in nephrectomized rats and paired sham-nephrectomized control animals under pentobarbitone anaesthesia. 2. Both threshold and slope of the angiotensin I dose—response curves were decreased at 15–27 h after nephrectomy. 3. The ratio of renin clearance (determined during renin infusions) in the nephrectomized rat to that in the paired sham-nephrectomized control animals was 0·49 ± 0·03 (sem), P < 0·001 (n = 12 pairs). 4. Both factors contribute towards the prolongation of the blood pressure increase after intravenously administered renin in the nephrectomized animal.


2001 ◽  
Vol 2 (1_suppl) ◽  
pp. S204-S210 ◽  
Author(s):  
William F van Rodijnen ◽  
Ton A van Lambalgen ◽  
Marco E van Teijlingen ◽  
Geert-Jan Tangelder ◽  
Piet M ter Wee

Angiotensin II (Ang II) type 1 (AT1) receptor blockers differ in their affinity for the AT1-receptor, suggesting a dissimilar potency for inhibiting Ang II-induced vascular constriction. In the present study, we compared the effects of candesartan, irbesartan and losartan on the renal microvascular constriction to locally-formed Ang II, using isolated, perfused hydronephrotic rat kidneys. Addition of 1 nmol/L angiotensin I (Ang I, the precursor of Ang II) significantly reduced the diameters of interlobular arteries (ILAs; -47.6±2.6%), afferent arterioles (AAs; -43.6±2.3%) and efferent arterioles (EAs; -31.6±2.4%). Candesartan and irbesartan were more potent in antagonising the constriction to Ang I than losartan. By contrast, candesartan and irbesartan differed only slightly in potency. After a washing period of 60 minutes with drug-free medium, a second application of Ang I failed to induce vasoconstriction only in candesartan-treated kidneys. Pretreatment of hydronephrotic kidneys with candesartan, to further explore its antagonistic properties, shifted the dose-response curves of Ang II approximately 2 log units to the right without reducing the maximal Ang II-induced constriction of ILAs, AAs or EAs. Additionally, dose-response curves of Ang II were similar after short (10 minutes) and prolonged (60 minutes) preincubation with candesartan. Our findings indicate that candesartan and irbesartan are more potent inhibitors of renal microvascular constriction to locally-formed Ang II than losartan. The inhibitory effect of candesartan is more prolonged, suggesting a slow dissociation from the AT1-receptor. Additionally, candesartan was found to block the Ang II-induced constriction of renal microvessels in a surmountable manner.


1977 ◽  
Vol 52 (6) ◽  
pp. 571-576
Author(s):  
Barbara L. Slack ◽  
J. M. Ledingham

1. Dose—response curves for the pressor activity of angiotensin II have been determined in unanaesthetized rats receiving diets containing 2·5% (w/w) or 0·007% (w/w) sodium and administered in various sequences. 2. Dose—response curves were shifted to the left in rats on a high-, compared with a low-, sodium intake. This response was maintained for 7 days on changing from high to low sodium. 3. There was no difference in the relation between the fall of cardiac output and the rise of blood pressure in any of the experimental groups. 4. Dose—response curves for peripheral resistance showed the same directional change as seen for the pressor response in rats on high- and low-sodium diets. Since depression of cardiac output was proportional to the pressure rise, the absolute change in peripheral resistance was greater than the blood pressure response. The proportional changes were similar. 5. It is concluded that alterations in the pressor response to angiotensin caused by changes in sodium loading are attributable to changes in peripheral resistance and not to changes in the cardiac output response to the acute rise in blood pressure.


1992 ◽  
Vol 70 (5) ◽  
pp. 716-719 ◽  
Author(s):  
Aly Abdelrahman ◽  
Catherine C. Y. Pang

Losartan (DuP 753) and PD123177 are nonpeptide angiotensin (ANG) receptor ligands for subtypes of ANG II receptors ANG II-1 and ANG II-2, respectively. We examined the effects of losartan and PD123177 on dose – mean arterial pressure (MAP) response curves for ANG II and ANG III in eight groups (n = 6 each) of conscious rats. Saline (0.9% NaCl), losartan (1 × 10−6 and 9 × 10−6 mol/kg), and PD123177 (2 × 10−5 mol/kg) were i.v. bolus injected 15 min before the construction of ANG II dose–response curves in groups I, II, III, and IV, respectively. Groups V–VIII were treated similarly to I–IV except that ANG III was given in place of ANG II. Losartan dose dependently shifted the dose–response curves of ANG II and ANG III to the right with similar dissociation constants (−log KI of 6.6 ± 0.7 and 6.6 ± 0.1 mol/kg, respectively) and no change in the maxima. PD123177 affected neither maximum MAP nor ED50 values for ANG II or ANG III. Our results show that losartan but not PD123177 is a competitive antagonist of the MAP effects of ANG II and ANG III.Key words: nonpeptide angiotensin receptor antagonist, angiotensin II, angiotensin III, blood pressure, losartan.


1968 ◽  
Vol 46 (1) ◽  
pp. 67-69 ◽  
Author(s):  
André L. Gascon

The response of the isolated guinea pig ileum to angiotensin, bradykinin, eledoisin, and acetylcholine was studied before and during exposure to morin. Dose–response curves were made for each agonist in the presence of different concentrations of the flavonoid (1 to 8 μg/ml). Under these conditions, the responses of the ileum to eledoisin, angiotensin, and acetylcholine were modified to various degrees depending upon the concentration of morin. With morin 1 μg/ml, the effect of eledoisin was reduced, and the activity of this polypeptide progressively decreased with an increase in the concentration of the inhibitor. On the other hand, the activity of acetylcholine was potentiated while that of bradykinin and angiotensin was unchanged. With higher concentrations of morin (4 and 8 μg/ml), the effect of both angiotensin and acetylcholine was slightly reduced. On the rat blood pressure, morin did not modify the effect of agonists. From these results it is concluded that morin is a specific and noncompetitive inhibitor of eledoisin on the isolated guinea pig ileum.


1974 ◽  
Vol 32 (02/03) ◽  
pp. 356-365 ◽  
Author(s):  
F Haverkate ◽  
D. W Traas

SummaryIn the fibrin plate assay different types of relationships between the dose of applied proteolytic enzyme and the response have been previously reported. This study was undertaken to determine whether a generally valid relationship might exist.Trypsin, chymotrypsin, papain, the plasminogen activator urokinase and all of the microbial proteases investigated, including brinase gave a linear relationship between the logarithm of the enzyme concentration and the diameter of the circular lysed zone. A similar linearity of dose-response curves has frequently been found by investigators who used enzyme plate assays with substrates different from fibrin incorporated in an agar gel. Consequently, it seems that this linearity of dose-response curves is generally valid for the fibrin plate assay as well as for other enzyme plate bioassays.Both human plasmin and porcine tissue activator of plasminogen showed deviations from linearity of semi-logarithmic dose-response curves in the fibrin plate assay.


1962 ◽  
Vol 41 (1) ◽  
pp. 143-153 ◽  
Author(s):  
U. Henriques

ABSTRACT A bioassay of thyroid hormone has been developed using Xenopus larvae made hypothyroid by the administration of thiourea. Only tadpoles of uniform developmental rate were used. Thiourea was given just before the metamorphotic climax in concentrations that produced neoteni in an early metamorphotic stage. During maintained thiourea neotoni, 1-thyroxine and 1-triiodothyronine were added as sodium salts to the water for three days and at the end of one week the stage of metamorphosis produced was determined. In this way identical dose-response curves were obtained for the two compounds. No qualitative differences between their effects were noted except that triiodothyronine seemed more toxic than thyroxine in equivalent doses. Triiodothyronine was found to be 7–12 times as active as thyroxine.


2005 ◽  
Vol 8 (4) ◽  
pp. E269-E274 ◽  
Author(s):  
Sydney L. Gaynor ◽  
Gregory D. Byrd ◽  
Michael D. Diodato ◽  
Yosuke Ishii ◽  
Anson M. Lee ◽  
...  

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