Angiotensin II and bradykinin: interactions between two centrally active peptides

1983 ◽  
Vol 244 (2) ◽  
pp. R285-R291 ◽  
Author(s):  
R. E. Lewis ◽  
W. E. Hoffman ◽  
M. I. Phillips
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Pressor Response ◽  
Common Mechanism ◽  
Ang Ii ◽  
Active Peptides ◽  
Central Actions ◽  
Prostaglandin A2 ◽  
The Brain ◽  
Peptide Interaction

Two neuropeptides, bradykinin (BK) and angiotensin II (ANG II), produce an increase in blood pressure when injected into the brain ventricles. This study is an example of central peptide-peptide interaction and was carried out to determine if BK and ANG II share a common mechanism in the brain to control blood pressure and drinking in rats. Prior injection of saralasin [10 micrograms intraventricularly (ivt)] was found to enhance the pressor response to ivt BK (5 micrograms) by 44%. The same dose of saralasin attenuated the pressor response to ivt ANG II (200 ng) by 55%. 50 ng ANG II and 5 micrograms BK given together ivt did not significantly alter blood pressure or urine conductance compared to 50 ng ANG II alone. Drinking to ivt infusions of ANG II (14 ng/min) was significantly attenuated when combined with BK (0.7 micrograms or 2.8 micrograms/min). Pretreatment with 10 micrograms indomethacin ivt diminished the pressor response to 5 micrograms ivt BK. Prostaglandin E2 (1.4 micrograms/min), but not prostaglandin A2, inhibited drinking to 14 ng/min ivt infusions of ANG II. The results suggest that ANG II and BK share an interrelationship with respect to their central actions: ANG II inhibits the BK pressor response and BK acts to inhibit drinking induced by ANG II. Prostaglandins of the E series may mediate these central actions of bradykinins.

Cardiovascular actions of microinjections of angiotensin II in the brain stem of rats

1984 ◽  
Vol 246 (5) ◽  
pp. R811-R816 ◽  
Author(s):  
R. Casto ◽  
M. I. Phillips
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Angiotensin Ii ◽  
Brain Stem ◽  
Nucleus Tractus Solitarius ◽  
Area Postrema ◽  
Cardiovascular Response ◽  
Pressor Response ◽  
Ang Ii ◽  
The Brain

The blood pressure and heart rate responses to microinjection of angiotensin II (ANG II) into the brain stem of urethan-anesthetized rats were studied. Microinjection of ANG II into the area postrema (AP) resulted in significant elevation of blood pressure and significant reduction of heart rate. Microinjection into the region of the nucleus tractus solitarius (NTS) yielded a significant dose-dependent elevation in blood pressure and consistent increases in heart rate. The response to microinjection of ANG II into the region of the NTS was not due to leakage into the peripheral circulation, since intravenous administration of the ANG II antagonist, saralasin, did not attenuate the response. In fact, the cardiovascular response was increased after peripheral ANG II blockade, and the heart rate, which was consistently but not significantly elevated by NTS injection alone, was significantly elevated after saralasin pretreatment. Thermal ablation of the AP did not change the heart rate or the pressor response to microinjection of ANG II into the region of the NTS, indicating that the response was not mediated through the AP.

Central angiotensin II and PGE2 act independently to increase blood pressure in conscious sheep

1987 ◽  
Vol 252 (1) ◽  
pp. R73-R77
Author(s):  
B. A. Breuhaus ◽  
J. E. Chimoskey
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Arterial Pressure ◽  
Pressor Response ◽  
Renin Angiotensin System ◽  
Cyclooxygenase Inhibitors ◽  
Ang Ii ◽  
Intracerebroventricular Infusion ◽  
Flunixin Meglumine ◽  
The Brain

Conscious adult female sheep chronically prepared with nonocclusive indwelling vascular and cerebroventricular catheters were used to determine whether centrally administered prostaglandin E2 (PGE2) increases blood pressure by activation of the brain renin angiotensin system or whether centrally administered angiotensin II (ANG II) increases blood pressure by stimulating prostaglandin synthesis in the brain. Intracerebroventricular (ivt) ANG II, 50 ng X kg-1 X min-1, increased arterial pressure 23 mmHg (P less than 0.01) 30 min after the start of infusion. Infusion of the ANG II antagonist [Sar1-Thr8]ANG II (sarthran), 1,000 ng X kg-1 X min-1 ivt, had no effect on arterial pressure when given by itself but reduced the ivt ANG II-induced pressor response to 5 mmHg (P less than 0.05) when the two peptides were infused at the same time. Intracerebroventricular infusion of sarthran did not alter the pressor responses to intracarotid (ic) PGE2 or to ivt PGE2. Blood pressure increased 21 mmHg (P less than 0.01) 30 min after the start of PGE2 infusion when PGE2 was given ic by itself, compared with 17 mmHg (P less than 0.01) when PGE2 was given ic at the same time as sarthran was given ivt. Blood pressure increased 14 mmHg (P less than 0.01) 30 min after the start of PGE2 infusion when PGE2 was given ivt by itself, compared with 16 mmHg (P less than 0.01) when PGE2 was given ivt at the same time as sarthran was given ivt. Pretreatment with the cyclooxygenase inhibitors indomethacin, 4 mg/kg sc, or flunixin meglumine, 3 mg/kg iv, did not alter the ivt ANG II-induced pressor response.(ABSTRACT TRUNCATED AT 250 WORDS)

Mechanisms of the central pressor action of angiotensin II in conscious rats

1984 ◽  
Vol 246 (1) ◽  
pp. R56-R62 ◽  
Author(s):  
R. W. Lappe ◽  
M. J. Brody
Keyword(s):  
Angiotensin Ii ◽  
Pressor Response ◽  
Ang Ii ◽  
Blood Flows ◽  
Abdominal Aortic ◽  
Regional Blood Flows ◽  
Regional Vascular Resistance ◽  
Central Actions ◽  
Vascular Beds ◽  
The Brain

Previous studies have demonstrated that, due to a central action, angiotensin II (ANG II) infused via the carotid artery of the rat elicited a greater pressor response than ANG II infused via the abdominal aorta. In the present study, regional vascular resistance responses to carotid and abdominal aortic infusions of ANG II and angiotensin I (ANG I) were compared in conscious unrestrained rats. Miniaturized pulsed Doppler flow probes were used to record regional blood flows. Carotid and aortic infusions caused vasoconstriction in the hindquarters, renal, and mesenteric vascular beds; the carotid route resulted in greater increases in arterial pressure and regional vascular resistances. The enhanced vasoconstrictor responses to carotid infusions of ANG II were significantly attenuated by systemic hexamethonium or central saralasin. Unlike ANG II, carotid and aortic infusions of ANG I produced equivalent regional vasoconstrictor responses not affected by central saralasin. It is concluded that in addition to its peripheral effects, central actions of ANG II induce neurally mediated vasoconstriction of the hindquarters, renal, and mesenteric vascular beds. Central effects of ANG II do not appear to result from conversion in the brain of blood-borne ANG I.

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 P152: Aminopeptidase A in the Brain Exerts Cardiovascular Action via Degradation of Kallidin to Bradykinin

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Takuto Nakamura ◽  
Masanobu Yamazato ◽  
Yusuke Ohya
Keyword(s):  
Blood Pressure ◽  
Pressor Response ◽  
Cardiovascular Regulation ◽  
Receptor Blocker ◽  
Ang Ii ◽  
Aminopeptidase A ◽  
Hoe 140 ◽  
Wistar Kyoto ◽  
The Brain

Objective: Aminopeptidase A (APA) degrades of various sympathomodulatory peptides such as angiotensin (Ang) II, cholecystkinin-8, neurokinin B and kallidin. APA activity is increased in the brain of hypertensive rats. A centrally acting APA inhibitor prodrug is currently under investigation in clinical trial for treatment of hypertension. In previous reports, a role of APA in the brain on cardiovascular regulation was researched focus on only renin-angiotensin system. We previously reported that intracerebroventricular(icv) administration of APA increased blood pressure and that this pressor response was partially blocked by angiotensin receptor blocker. In this study, we evaluated a role of APA on cardiovascular regulation focusing on peptides other than Ang II. Method: Eleven weeks old Wistar Kyoto rats were used. We icv administrated 800 ng/8 μL of APA after pretreatment of following drugs, i) 8μL of artificial cerebrospinal fluid (aCSF) as a control, ii) 80 nmol/8 μL of amastatin which is a non-specific aminopeptidase inhibitor, iii) 1 nmol/8 μL of HOE-140 which is a bradykinin receptor blocker to evaluate the involvement of degradation of kallidin to bradykinin by APA. Result: i) Icv administration of APA after pretreatment of aCSF increased blood pressure rapidly. Blood pressure reached a peak within 1 minute. The elevated blood pressure decreased gradually and reached baseline blood pressure in 10 minutes. A peak pressor response is 25.5±1.4 mmHg (n=5). ii) Icv pretreatment of amastatin or HOE-140 did not change the blood pressure. A peak pressor response induced by APA is 13.1±4.1 mmHg (n=6, p<0.05 vs aCSF). iii) Icv pretreatment of HOE-140 did not change the blood pressure. A peak pressor response induced by APA is 21.2±1.8 mmHg (n=4, p<0.05 vs aCSF). Conclusion: 1) Icv administration of APA increased blood pressure by APA enzymatic activity. 2) Cardiovascular regulation of APA in the brain is due to not only degradation of Ang II to Ang III but also degradation of kallidin to bradykinin. Clinical implication: We think inhibition of APA in the brain may be a unique therapeutic target which affects several cardiovascular peptides in the brain.

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.

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.

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.

Angiotensin II attenuates baroreflexes at nucleus tractus solitarius of rats

1986 ◽  
Vol 250 (2) ◽  
pp. R193-R198 ◽  
Author(s):  
R. Casto ◽  
M. I. Phillips
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Baroreflex Sensitivity ◽  
Nucleus Tractus Solitarius ◽  
Ang Ii ◽  
Spontaneously Hypertensive ◽  
Baroreceptor Reflexes ◽  
Dose Dependent Increase ◽  
Dose Dependent ◽  
The Brain

Microinjection of angiotensin II (ANG II) into the nucleus tractus solitarius (NTS) has been shown to produce a dose-dependent increase in blood pressure and heart rate. We have tested the effect of subpressor infusions of ANG II (10 ng . kg-1 . min-1) in the NTS on reflex bradycardia after intravenous administration of the vasoconstrictor phenylephrine (1-12 micrograms) in normotensive urethan-anesthetized rats. ANG II within the brain is thought to contribute to the decreased baroreflex sensitivity in spontaneously hypertensive rats (SHR). The sensitivity of the baroreflex was significantly decreased by the infusion of ANG II (1.01 +/- 0.08) compared with control (2.41 +/- 0.51) in the normotensive animals. Baroreflex sensitivity was significantly decreased in SHR (0.40 +/- 0.21) compared with normotensive animals. We conclude that ANG II within the NTS can inhibit the function of baroreceptor reflexes in normotensive animals, suggesting that the endogenous peptide may perform an inhibitory role in the baroreflex arc, and this is further evidence that central ANG II is involved in blood pressure of SHR.

scholarly journals Excess of Aminopeptidase A in the Brain Elevates Blood Pressure via the Angiotensin II Type 1 and Bradykinin B2 Receptors without Dipsogenic Effect

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Takuto Nakamura ◽  
Masanobu Yamazato ◽  
Akio Ishida ◽  
Yusuke Ohya
Keyword(s):  
Blood Pressure ◽  
Pressor Response ◽  
Drinking Behavior ◽  
Receptor Blocker ◽  
Ang Ii ◽  
Aminopeptidase A ◽  
Hoe 140 ◽  
B2 Receptors ◽  
The Brain

Aminopeptidase A (APA) cleaves angiotensin (Ang) II, kallidin, and other related peptides. In the brain, it activates the renin angiotensin system and causes hypertension. Limited data are available on the dipsogenic effect of APA and pressor effect of degraded peptides of APA such as bradykinin. Wistar-Kyoto rats received intracerebroventricular (icv) APA in a conscious, unrestrained state after pretreatment with (i) vehicle, (ii) 80 μg of telmisartan, an Ang II type-1 (AT1) receptor blocker, (iii) 800 nmol of amastatin, an aminopeptidase inhibitor, and (iv) 1 nmol of HOE-140, a bradykinin B2 receptor blocker. Icv administration of 400 and 800 ng of APA increased blood pressure by 12.6 ± 3.0 and 19.0 ± 3.1 mmHg, respectively. APA did not evoke drinking behavior. Pressor response to APA was attenuated on pretreatment with telmisartan (vehicle: 22.1 ± 2.2 mmHg versus telmisartan: 10.4 ± 3.2 mmHg). Pressor response to APA was also attenuated with amastatin and HOE-140 (vehicle: 26.5 ± 1.1 mmHg, amastatin: 14.4 ± 4.2 mmHg, HOE-140: 16.4 ± 2.2 mmHg). In conclusion, APA increase in the brain evokes a pressor response via enzymatic activity without dipsogenic effect. AT1 receptors and B2 receptors in the brain may contribute to the APA-induced pressor response.

Sign in / Sign up

Export Citation Format

Share Document