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.

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.

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.

Fastigial nucleus cardiovascular response and brain stem lesions in the beagle

1986 ◽  
Vol 250 (2) ◽  
pp. H231-H239 ◽  
Author(s):  
K. J. Dormer ◽  
J. A. Andrezik ◽  
R. J. Person ◽  
J. T. Braggio ◽  
R. D. Foreman
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Electrical Stimulation ◽  
Brain Stem ◽  
Kainic Acid ◽  
Cardiovascular Response ◽  
Pressor Response ◽  
Fastigial Nucleus ◽  
Reticular Nucleus ◽  
A5 Area

Changes in the excitatory cardiovascular response (heart rate, arterial blood pressure, left ventricular pressure, and LV dP/dt as an index of myocardial contractility) resulting from electrical stimulation of the cerebellar fastigial nucleus (FN) were recorded after placement of DC or radio-frequency lesions or after microinjections of kainic acid into brain stem areas that receive FN projections and have been shown to be involved in central cardiovascular control. FN-induced increases in heart rate, blood pressure, and contractility were reduced or abolished by lesions made in the restiform body or the A5 area, which is homologous to the catecholamine-containing region in cats and rats. Lesions in the paramedian reticular nucleus, rostral and caudal to obex, failed to reduce the FN cardiovascular response. Nucleus of the solitary tract lesions augmented the FN pressor response and tachycardia. Kainic acid (1 microliter of 100 mM solution) caused profound depression of heart rate, blood pressure, and contractility and reduced or eliminated the FN-induced cardiovascular response when injected into the A5 area, previously identified by the pressor response following electrical stimulation. We concluded from these observations that a descending fastigiobulbar sympathoexcitatory pathway courses through a previously identified A5 pressor area that is also capable of a depressor response when the cell bodies alone are activated.

Cardiovascular consequences of microinjection of vasopressin and angiotensin II in the area postrema

1993 ◽  
Vol 265 (3) ◽  
pp. R625-R631 ◽  
Author(s):  
V. L. Lowes ◽  
L. E. McLean ◽  
N. W. Kasting ◽  
A. V. Ferguson
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Angiotensin Ii ◽  
Area Postrema ◽  
Blood Pressure Response ◽  
Pressor Response ◽  
Systemic Administration ◽  
Pressure Response ◽  
Arterial Blood ◽  
At1 Antagonist

Microinjection of angiotensin II (ANG II) into the area postrema (AP) of urethan-anesthetized male Sprague-Dawley rats elicited statistically significant increases in mean arterial blood pressure at doses ranging from 10 pg to 500 ng (10 pg, mean +/- SE, 10.8 +/- 1.1 mmHg, P < 0.001; 250 ng, 15.2 +/- 2.6 mmHg, P < 0.001). Heart rate was also significantly increased at doses > 10 pg, although these increases were not dose dependent. Systemic administration of losartan (Dup-753), an AT1 antagonist, was able to significantly reduce the pressor response to 250 ng ANG (post-losartan: 81.9 +/- 9.5% reduction in blood pressure response, P < 0.0001), whereas PD123319, an AT2 antagonist, was without significant effect (P > 0.1). Microinjection of vasopressin (VP) (10 pg-500 ng) into the AP also resulted in statistically significant increases in blood pressure at doses ranging from 10 to 100 pg (10 pg, 7.0 +/- 1.5 mmHg, P < 0.05) and 100-500 ng (250 ng, 12.2 +/- 1.8 mmHg, P < 0.0001). Small but significant changes in heart rate were observed only at 100 pg and 100 ng. Systemic administration of a V1 antagonist significantly attenuated the increases in blood pressure in response to 50, 100, and 250 ng VP (250 ng, post-V1 antagonist: 66.4 +/- 8.6% reduction in blood pressure response, P < 0.001), whereas [desamino,D-Arg8]vasopressin (DDAVP), a V2 agonist, had a depressor effect when microinjected directly into the AP (250 ng, -9.9 +/- 1.6 mmHg, P < 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

Role of the area postrema in angiotensin II modulation of baroreflex control of heart rate in conscious mice

2003 ◽  
Vol 284 (3) ◽  
pp. H1003-H1007 ◽  
Author(s):  
Baojian Xue ◽  
Hope Gole ◽  
Jaya Pamidimukkala ◽  
Meredith Hay
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Angiotensin Ii ◽  
Arterial Pressure ◽  
Area Postrema ◽  
Ang Ii ◽  
Baroreflex Control ◽  
Arterial Blood ◽  
Intravenous Infusions

This study reports the effects of angiotensin II (ANG II), arginine vasopression (AVP), phenylephrine (PE), and sodium nitroprusside (SNP) on baroreflex control of heart rate in the presence and absence of the area postrema (AP) in conscious mice. In intact, sham-lesioned mice, baroreflex-induced decreases in heart rate due to increases in arterial pressure with intravenous infusions of ANG II were significantly less than those observed with similar increases in arterial pressure with PE (slope: −3.0 ± 0.9 vs. −8.1 ± 1.5 beats · min−1 · mmHg−1). Baroreflex-induced decreases in heart rate due to increases in arterial pressure with intravenous infusions of AVP were the same as those observed with PE in sham animals (slope: −5.8 ± 0.7 vs. −8.1 ± 1.5 beats · min−1 · mmHg−1). After the AP was lesioned, the slope of baroreflex inhibition of heart rate was the same whether pressure was increased with ANG II, AVP, or PE. The slope of the baroreflex-induced increases in heart rate due to decreases in arterial blood pressure with SNP were the same in sham- and AP-lesioned animals. These results indicate that, similar to other species, in mice the ability of ANG II to acutely reset baroreflex control of heart rate is dependent on an intact AP.

Effects of angiotensin II on autonomic components of nasopharyngeal stimulation in male conscious rabbits

2005 ◽  
Vol 98 (5) ◽  
pp. 1607-1611 ◽  
Author(s):  
Tarek M. Mousa ◽  
Lie Gao ◽  
Kurtis G. Cornish ◽  
Irving H. Zucker
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Angiotensin Ii ◽  
Cigarette Smoke ◽  
Pressor Response ◽  
Sympathetic Neurons ◽  
Cardiovascular Responses ◽  
Ang Ii ◽  
Before And After ◽  
Conscious Rabbits

Angiotensin II (ANG II) is known to activate central sympathetic neurons. In this study we determined the effects of ANG II on the autonomic components of the cardiovascular responses to stimulation of nasopharyngeal receptors with cigarette smoke. Experiments were carried out in conscious New Zealand White rabbits instrumented to record arterial pressure and heart rate. Rabbits were exposed to 50 ml of cigarette smoke before and after subcutaneous osmotic minipump delivery of ANG II at a dose of 50 ng·kg−1·min−1 for 1 wk in one group and intracerebroventricular (icv) infusion at a dose of 100 pmol/min for 1 h in a second group. The responses were compared before and after heart rate was controlled by pacing. Autonomic components were evaluated by intravenous administration of atropine methyl bromide (0.2 mg/kg) and prazosin (0.5 mg/kg). ANG II given either systemically or icv significantly blunted the pressor response to smoke ( P < 0.05) when the bradycardic response was prevented. This blunted response was not due to an absolute increase in baseline blood pressure after ANG II infusion (71.64 ± 11.6 vs. 92.1 ± 19.8 mmHg; P < 0.05) because normalization of blood pressure with sodium nitroprusside to pre-ANG II levels also resulted in a significantly blunted pressor response to smoke. The effect of smoke was α1-adrenergic receptor-mediated because it was essentially abolished by prazosin in both the pre- and the post-ANG II states ( P < 0.05). These results suggest that elevations in central ANG II reduce the sympathetic response to smoke in conscious rabbits. This effect may be due to an augmentation of baseline sympathetic outflow and a reduction in reflex sensitivity similar to the effect of ANG II on baroreflex function.

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)

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.

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