Action of Angiotensin Antagonists and Antiserum upon the Pressor Response to Renin: Further Evidence for the Local Generation of Angiotensin II

1974 ◽  
Vol 46 (2) ◽  
pp. 273-276 ◽  
Author(s):  
H. Thurston ◽  
J. D. Swales
Keyword(s):  
Blood Pressure ◽  
Molecular Weight ◽  
Angiotensin Ii ◽  
Pressor Response ◽  
Low Molecular Weight ◽  
Angiotensin Ii Antagonist ◽  
Local Generation

1. Bilaterally nephrectomized rats were infused with a pressor dose of renin. The blood pressure was only partially restored to normal by sufficient angiotensin II antiserum to block the pressor response to exogenous angiotensin II. 2. A reduced pressor response still occurred when animals which had been pretreated with angiotensin II antiserum were infused with renin. 3. Infusion of an angiotensin II antagonist (1-sarcosine-8-alanine angiotensin II) restored the blood pressure of both groups of animals to normal. 4. These observations support the hypothesis that renin generates angiotensin II at a local vascular level. This site is inaccessible to antisera, but accessible to the low-molecular-weight antagonist.

Changes in Blood Pressure in Relation to Vascular and Plasma Renin after Renin Injection in Rats

1982 ◽  
Vol 63 (s8) ◽  
pp. 153s-156s ◽  
Author(s):  
M. Loudon ◽  
R. F. Bing ◽  
J. D. Swales ◽  
H. Thurston
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Pressor Response ◽  
Plasma Renin ◽  
Aortic Tissue ◽  
Relative Importance ◽  
Bilateral Nephrectomy ◽  
Single Intravenous Injection ◽  
Angiotensin Ii Antagonist ◽  
Renal Origin

1. To assess the relative importance of vascular as opposed to plasma renin, groups of conscious rats received a single intravenous injection of partially purified rat renin 18 h after bilateral nephrectomy. Blood pressure was monitored continuously and plasma and aortic renin concentrations were determined at 1, 3, 6 or 9 h after injection. In separate groups of rats the effect of the competitive angiotensin II antagonist, saralasin, on blood pressure was measured 3 or 6 h after renin injection. 2. Blood pressure remained elevated for up to 6 h after renin injection, returning to normal by 9 h. Saralasin infusion reversed the rise in blood pressure at both 3 and 6 h after injection. 3. Aortic renin concentration followed the pattern of the pressor response whereas plasma renin concentration had returned to subnormal values by 3 h. 4. Circulating renin of renal origin is taken up by aortic tissue. The pressor response to exogenous renin in rats after bilateral nephrectomy is not related to changes in plasma renin but is similar in duration to the persistence of aortic renin-like activity and can be blocked by saralasin at both 3 and 6 h after injection.

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.

Centrally induced cardiovascular and sympathetic responses to hydrocortisone in rats

1983 ◽  
Vol 245 (6) ◽  
pp. H1013-H1018 ◽  
Author(s):  
H. Takahashi ◽  
K. Takeda ◽  
H. Ashizawa ◽  
A. Inoue ◽  
S. Yoneda ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Angiotensin Ii ◽  
Sympathetic Nerve ◽  
Enzyme Inhibitor ◽  
Renin Angiotensin System ◽  
Angiotensin System ◽  
Angiotensin I Converting Enzyme ◽  
Angiotensin Ii Antagonist ◽  
Dose Dependent

Central effects of hydrocortisone were investigated by injecting it intracerebroventricularly (icv) while recording blood pressure and heart rate in awake rats. Dose-dependent increases in both blood pressure and heart rate occurred following injections of hydrocortisone. Pretreatment by icv injections of the angiotensin II antagonist, [Sar1-Ile8]angiotensin II, completely abolished vasopressor responses to subsequent injections of hydrocortisone. When rats were later anesthetized with urethan to allow recording of abdominal sympathetic nerve activity, hydrocortisone produced vasopressor responses accompanied by corresponding increases in sympathetic nerve firing, which were also abolished by central pretreatment with either [Sar1-Ile8]angiotensin II or angiotensin I converting-enzyme inhibitor, captopril. These results indicate that centrally administered hydrocortisone stimulates the brain renin-angiotensin system to produce vasopressor responses by increasing sympathetic nerve firing.

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.

Vascular response to infusions of a nonextravasating hemoglobin polymer

2002 ◽  
Vol 93 (4) ◽  
pp. 1479-1486 ◽  
Author(s):  
Barbara Matheson ◽  
Herman E. Kwansa ◽  
Enrico Bucci ◽  
Annette Rebel ◽  
Raymond C. Koehler
Keyword(s):  
Molecular Weight ◽  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Arterial Pressure ◽  
Exchange Transfusion ◽  
Pressor Response ◽  
Low Molecular Weight ◽  
Bovine Hemoglobin ◽  
Pial Arterioles ◽  
Awake Cats

The clinical utility of cross-linked tetrameric hemoglobin solutions is limited by peripheral vasoconstriction thought to be due to scavenging of nitric oxide. In addition, transfusion of crude preparations of hemoglobin polymers can cause arterial hypertension. We tested the hypothesis that eliminating low-molecular-weight components from the polymer solution would prevent extravasation and its associated pressor response. A zero-link polymer of bovine hemoglobin was developed without chemical linkers left between the tetramers. Transfusion of unprocessed preparations of these polymers in rats resulted in appearance of the polymer in the renal hilar lymph. However, eliminating the low-molecular-weight components with a 300-kDa diafiltration resulted in an average hydrodynamic radius of 250 Å and in undetectable levels of polymer in hilar lymph. Exchange transfusion in anesthetized rats and cats and in awake cats produced no increase in arterial pressure. In anesthetized cats, exchange transfusion with an albumin solution reduced hematocrit from 30 to 18%, increased cerebral blood flow, and dilated pial arterioles. In contrast, reducing hematocrit by transfusing the diafiltered polymer did not increase cerebral blood flow as pial arterioles constricted. These results are consistent with the hypothesis that the increase in arterial pressure associated with cell-free hemoglobin transfusion depends on hemoglobin extravasation. Constriction observed in the cerebrovascular bed with a nonextravasating hemoglobin polymer at low hematocrit is presumably a regulatory response to prevent overoxygenation at low blood viscosity.

In vitro and in vivo inhibition of renin by fatty acids.

1978 ◽  
Vol 234 (6) ◽  
pp. E593 ◽  
Author(s):  
T A Kotchen ◽  
W J Welch ◽  
R T Talwalkar
Keyword(s):  
Blood Pressure ◽  
Fatty Acids ◽  
Linoleic Acid ◽  
Angiotensin Ii ◽  
Neutral Lipids ◽  
Pressor Response ◽  
Arterial Blood ◽  
Arachidonic Acids

Circulating neutral lipids inhibit the in vitro renin reaction. To identify the inhibitor(s), free fatty acids were added to human renin and homologous substrate. Capric, lauric, palmitoleic, linoleic, and arachidonic acids each inhibited the rate of angiotensin I production in vitro (P less than 0.01). Inhibition by polysaturated fatty acids (linoleic and arachidonic) was less (P less than 0.01) after catalytic hydrogenation of the double bonds. To evaluate an in vivo effect of renin inhibition intra-arterial blood pressure responses to infusions of renin and angiotensin II (5.0 microgram) were measured in anephric rats (n = 6) before and after infusion of linoleic acid (10 mg iv). Mean increase of blood pressure to angiotensin II before (75 mmHg +/- 9) and after (90 +/- 12) linoleic acid did not differ (P greater than 0.05). However, the pressor response to renin after linoleic acid (18 +/- 3) was less (P less than 0.00)) than that before (102 +/- 13). In summary, several fatty acids inhibit the in vitro renin reaction, and in part inhibition is dependent on unsaturation. Linoleic acid also inhibits the in vivo pressor response to renin. These results suggest that fatty acids may modify the measurement of plasma renin activity and may also affect angiotensin production in vivo.

Two Sites of Cardiovascular Action of Angiotensin II in the Brain of the Dog

1973 ◽  
Vol 44 (4) ◽  
pp. 417-420 ◽  
Author(s):  
P. L. Gildenberg ◽  
C. M. Ferrario ◽  
J. W. McCubbin
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Lateral Ventricle ◽  
Area Postrema ◽  
Pressor Response ◽  
Cerebral Ventricle ◽  
Vertebral Arteries ◽  
Adjacent Structures ◽  
The Brain ◽  
Lateral Cerebral Ventricle

1. Infusion of angiotensin into both vertebral arteries or into a lateral cerebral ventricle of dogs anaesthetized with morphine-chloralose elicited a centrally mediated rise in blood pressure. 2. Heat coagulation of the area postrema and immediately adjacent structures abolished the pressor response to infusion of angiotensin into the circulation of the vertebral arteries, but did not alter the pressor response when the peptide was delivered into a cerebral lateral ventricle; transection of the midbrain eliminated the latter response but not the former. 3. It is concluded that there are at least two areas in the dog's brain that respond to angiotensin by inducing a raised blood pressure.

Calcium Antagonists Decrease Adrenal and Vascular Responsiveness to Angiotensin II in Normal Man

1981 ◽  
Vol 61 (s7) ◽  
pp. 65s-68s ◽  
Author(s):  
J. A. Millar ◽  
Kathleen McLean ◽  
J. L. Reid
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Pulse Rate ◽  
Calcium Antagonists ◽  
Pressor Response ◽  
Plasma Potassium ◽  
Normal Subjects ◽  
Rank Test ◽  
Vascular Responsiveness ◽  
Signed Rank Test

1. The effect of the calcium antagonist nifedipine on the pressor and aldosterone responses to angiotensin II was studied in six normal subjects. 2. Blood pressure, pulse rate and plasma aldosterone, potassium and cortisol were measured during paired consecutive infusions of angiotensin II (5, 10 and 20 ng min−1 kg−1) on two separate occasions. Nifedipine (20 mg by mouth) was given, 30 min before the second set of infusions. 3. After nifedipine there were reciprocal changes in supine resting blood pressure (−7 mm Hg) and pulse rate (+18 min−1) and a significant decrease in the pressor response to angiotensin II (P &lt; 0.05; Wilcoxon signed rank test). 4. Basal levels of aldosterone were not changed by nifedipine, but the response to angiotensin II was significantly attenuated (P &lt; 0.05). Nifedipine had no effect on plasma potassium or cortisol. 5. Transmembrane movement of calcium is involved in the aldosterone response to angiotensin II in man. Calcium antagonists may lower blood pressure via decreased adrenal responsiveness to angiotensin II as well as by peripheral vasodilatation.

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