Mechanism of pressor effects by angiotensin in the nucleus tractus solitarius of rats

1984 ◽  
Vol 247 (3) ◽  
pp. R575-R581 ◽  
Author(s):  
R. Casto ◽  
M. I. Phillips
Keyword(s):  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Nucleus Tractus Solitarius ◽  
Pressor Response ◽  
Dose Range ◽  
Ang Ii ◽  
Sympathetic Activation ◽  
Vasopressin Antagonist ◽  
Hypophysectomized Rats ◽  
Intact Rats

We recently reported that microinjection of angiotensin II (ANG II) into the nucleus tractus solitarius (NTS) results in an increase in mean arterial pressure (MAP) in urethan-anesthetized rats in a dose range of 50-500 ng. To investigate the mechanism of this response, hexamethonium (20 mg/kg iv) was used to inhibit sympathetic activation. There was a highly significant (P less than 0.001) reduction in the magnitude of the pressor response (4.7 +/- 1.1 mmHg) compared with preblockade ANG II (500 ng) responses (15.5 +/- 1.6 mmHg). A vasopressin antagonist and hypophysectomized rats were used to study the contribution of pituitary vasopressin. Injection of 500 ng ANG II in hypophysectomized rats produced a pressor response (14.8 +/- 3.2 mmHg) indistinguishable from that in intact controls (15.5 +/- 1.6 mmHg). Pretreatment with the vasopressin antagonist d(CH2)5Tyr(Me)AVP (1 microgram iv) in intact rats also had no effect on the magnitude of the pressor response (15.7 +/- 1.7 mmHg). Microinjection of ANG I and II produces an increase in arterial pressure. It is concluded that the angiotensin pressor response in the NTS is mediated by activation of descending sympathetic fibers and is not dependent on release of blood-borne pressor agents from the pituitary.

Central vasopressin in the modulation of catecholamine release in conscious rats

1985 ◽  
Vol 63 (12) ◽  
pp. 1501-1505 ◽  
Author(s):  
Kathryn A. King ◽  
Gordon Mackie ◽  
Catherine C. Y. Pang ◽  
Richard A. Wall
Keyword(s):  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Paraventricular Nucleus ◽  
Fourth Ventricle ◽  
Nucleus Tractus Solitarius ◽  
Pressor Response ◽  
Plasma Concentrations ◽  
Cardiovascular Reflex ◽  
Baroreceptor Reflexes ◽  
Reflex System

Neurons containing arginine vasopressin (AVP) have been shown to project from the paraventricular nucleus of the hypothalamus to the nucleus tractus solitarius (NTS) in the medulla. We investigated whether AVP acts in brain stem regions to influence sympathoadrenal outflow. Cannulae were implanted into the fourth ventricle of rats 7 days prior to the experiment. The effects of intracerebroventricular (icv) injections of AVP, the vehicle, and AVP antagonist, d(CH2)5Tyr(Me)AVP, on mean arterial pressure (MAP) and plasma noradrenaline (NA) and adrenaline (A) levels were determined in conscious unrestrained rats. Injections of AVP (icv, 23 and 73 ng/kg) but not the vehicle increased MAP and plasma NA and A levels. In contrast, iv injection of AVP increased MAP but decreased plasma concentrations of A and NA. The pressor response to icv injection of AVP was abolished by prior icv injection of AVP antagonist. Injection of AVP antagonist (icv, 0.5 and 1.5 μg/kg) had no effect on MAP or plasma NA or A levels. These results show that centrally injected AVP activates sympathoadrenal outflow, possibly via an inhibition of baroreceptor reflexes. Since centrally administered AVP antagonist did not influence MAP or plasma NA or A levels, it appears that endogenously released AVP does not have a tonic influence on central cardiovascular reflex system in conscious, unrestrained rats.

Activation of GABAA but not GABAB receptors in the NTSblocked bradycardia of chemoreflex in awake rats

1999 ◽  
Vol 276 (6) ◽  
pp. H1902-H1910 ◽  
Author(s):  
João Carlos Callera ◽  
Leni G. H. Bonagamba ◽  
Anne Nosjean ◽  
Raul Laguzzi ◽  
Benedito H. Machado
Keyword(s):  
Heart Rate ◽  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Nucleus Tractus Solitarius ◽  
Pressor Response ◽  
Potassium Cyanide ◽  
Gabab Receptors ◽  
Basal Heart Rate ◽  
Pressor Responses ◽  
Awake Rats

In the present study we analyzed effects of bilateral microinjections of muscimol (a GABAA agonist) and baclofen (a GABAB agonist) into the nucleus tractus solitarius (NTS) on bradycardic and pressor responses to chemoreflex activation (potassium cyanide, 40 μg/rat iv) in awake rats. Bilateral microinjections of muscimol (25 and 50 pmol/50 nl) into the NTS increased baseline mean arterial pressure (MAP): 119 ± 8 vs. 107 ± 2 mmHg ( n = 6) and 121 ± 8 vs. 103 ± 3 mmHg ( n= 6), respectively. Muscimol at 25 pmol/50 nl reduced the bradycardic response to chemoreflex activation 5 min after microinjection; with 50 pmol/50 nl the bradycardic response to chemoreflex activation was reduced 5, 15, 30, and 60 min after microinjection. Neither muscimol dose produced an effect on the pressor response of the chemoreflex. Effects of muscimol (50 pmol/50 nl) on basal MAP and on the bradycardic response of the chemoreflex were prevented by prior microinjection of bicuculline (a GABAA antagonist, 40 pmol/50 nl) into the NTS. Bilateral microinjections of baclofen (12.5 and 25 pmol/50 nl) into the NTS produced an increase in baseline MAP [137 ± 9 vs. 108 ± 4 ( n= 7) and 145 ± 5 vs. 105 ± 2 mmHg ( n = 7), respectively], no changes in basal heart rate, and no effects on the bradycardic response; 25 pmol/50 nl only attenuated the pressor response to chemoreflex activation. The data show that activation of GABAA receptors in the NTS produces a significant reduction in the bradycardic response, whereas activation of GABAB receptors produces a significant reduction in the pressor response of the chemoreflex. We conclude that 1) GABAA but not GABAB plays an inhibitory role in neurons of the lateral commissural NTS involved in the parasympathetic component of the chemoreflex and 2) attenuation of the pressor response of the chemoreflex by activation of GABAB receptors may be due to inhibition of sympathoexcitatory neurons in the NTS or may be secondary to the large increase in baseline MAP produced by baclofen.

scholarly journals Comparison of arterial pressure and plasma ANG II responses to three methods of subcutaneous ANG II administration

2014 ◽  
Vol 307 (5) ◽  
pp. H670-H679 ◽  
Author(s):  
Marcos T. Kuroki ◽  
Gregory D. Fink ◽  
John W. Osborn
Keyword(s):  
Angiotensin Ii ◽  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Pressor Response ◽  
Infusion Pump ◽  
Pressure Profile ◽  
Experimental Hypertension ◽  
Ang Ii ◽  
Gradual Decline ◽  
Induced Hypertension

Angiotensin II (ANG II)-induced hypertension is a commonly studied model of experimental hypertension, particularly in rodents, and is often generated by subcutaneous delivery of ANG II using Alzet osmotic minipumps chronically implanted under the skin. We have observed that, in a subset of animals subjected to this protocol, mean arterial pressure (MAP) begins to decline gradually starting the second week of ANG II infusion, resulting in a blunting of the slow pressor response and reduced final MAP. We hypothesized that this variability in the slow pressor response to ANG II was mainly due to factors unique to Alzet pumps. To test this, we compared the pressure profile and changes in plasma ANG II levels during subcutaneous ANG II administration (150 ng·kg−1·min−1) using either Alzet minipumps, iPrecio implantable pumps, or a Harvard external infusion pump. At the end of 14 days of ANG II, MAP was highest in the iPrecio group (156 ± 3 mmHg) followed by Harvard (140 ± 3 mmHg) and Alzet (122 ± 3 mmHg) groups. The rate of the slow pressor response, measured as daily increases in pressure averaged over days 2–14 of ANG II, was similar between iPrecio and Harvard groups (2.7 ± 0.4 and 2.2 ± 0.4 mmHg/day) but was significantly blunted in the Alzet group (0.4 ± 0.4 mmHg/day) due to a gradual decline in MAP in a subset of rats. We also found differences in the temporal profile of plasma ANG II between infusion groups. We conclude that the gradual decline in MAP observed in a subset of rats during ANG II infusion using Alzet pumps is mainly due to pump-dependent factors when applied in this particular context.

scholarly journals Developmental Changes in Hemodynamic Responses and Cardiovagal Modulation during Isometric Handgrip Exercise

2010 ◽  
Vol 2010 ◽  
pp. 1-11 ◽  
Author(s):  
Styliani Goulopoulou ◽  
Bo Fernhall ◽  
Jill A. Kanaley
Keyword(s):  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Isometric Contraction ◽  
Pressor Response ◽  
Reflex Response ◽  
Group Differences ◽  
Handgrip Exercise ◽  
Isometric Handgrip ◽  
Isometric Handgrip Exercise ◽  
Pressor Reflex

The purpose of this study was to examine differences in pressor response and cardiovagal modulation during isometric handgrip exercise (IHG) between children and adults. Beat-to-beat heart rate (HR) and blood pressure were measured in 23 prepubertal children and 23 adults at baseline and during IHG. Cardiovagal modulation was quantified by analysis of HR variability. Mean arterial pressure responses to IHG were greater in adults compared to children (P<.05) whereas there were no group differences in HR responses (P>.05). Children had a greater reduction in cardiovagal modulation in response to IHG compared to adults (P<.05). Changes in mean arterial pressure during IHG were correlated with baseline cardiovagal modulation and force produced during isometric contraction (P<.05). In conclusion, differences in pressor reflex response between children and adults cannot be solely explained by differences in autonomic modulation and appear to be associated with factors contributing to the force produced during isometric contraction.

Abstract 477: Diverse Actions of the EP4 Prostaglandin E2 Receptor in Blood Pressure Control

Hypertension ◽  
2013 ◽  
Vol 62 (suppl_1) ◽  
Author(s):  
Marcela Herrera ◽  
Matthew A Sparks ◽  
Beverky H Koller ◽  
Thomas M Coffman
Keyword(s):  
Smooth Muscle ◽  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Smooth Muscle Cells ◽  
Prostaglandin E2 ◽  
Ductus Arteriosus ◽  
Muscle Cells ◽  
High Salt ◽  
Ang Ii ◽  
The Impact

Prostaglandin E2 (PGE2) is a major prostanoid produced by the kidney having the potential to influence renal blood flow, Na excretion, and thus mean arterial pressure (BP). PGE2 actions are mediated by four distinct E-prostanoid (EP) receptor isoforms: EP1-EP4. The EP4 receptor (EP4R) triggers macula densa stimulation of renin, induces vasodilation, and may inhibit epithelial sodium transport. Thus, the impact of EP4Rs on BP may differ with the sites of PGE2 synthesis and pattern of EP4R activation within the kidney. To examine the role of EP4R on BP regulation we generated EP4R-deficient mice. Because deletion of EP4R in utero causes peri-natal mortality due to persistent patent ductus arteriosus, we carried out conditional deletion by crossing EP4flox/flox with a transgenic line with tamoxifen-inducible Cre expression in all tissues. Resting mean arterial pressure (MAP) measured by radiotelemetry was increased by 5±1mm Hg (p<0.05) in mice with total-body EP4R-deficiency (EP4R-TBKO) vs. controls. In addition, EP4R-TBKOs had an exaggerated increase in MAP with high-salt (6% NaCl) feeding (MAP increase: 5±1 vs. 2±1mmHg for controls; p<0.05) and during angiotensin II (Ang II)-dependent hypertension (MAP increase: 37±2 vs. 24±3mmHg for controls; p<0.05). We next hypothesized that exaggerated hypertension in the EP4R-TBKOs was due to elimination of compensatory EP4R-depedent vasodilation mediated by direct actions in vascular smooth muscle cells (VSMCs). Accordingly, we generated mice lacking EP4R in VSMCs (EP4R-SMKOs) using EP4flox/flox and transgenic mice with tamoxifen-inducible expression of Cre limited to smooth muscle cells. In contrast to the EP4R-TBKOs, elimination of EP4R only from VSMC reduced resting MAP by 5±1mm Hg (p<0.04) but did not affect the BP response to high salt feeding (MAP change: 2±1 vs. 2±1 mm Hg; ns) or chronic Ang II infusion (MAP increase: 29±3 vs. 34±4 mm Hg; ns). Thus, the EP4R modulates resting MAP but its specific impact may vary between EP4R populations in different cell lineages. EP4Rs resist the development of salt- and Ang II-dependent hypertension. These anti-hypertensive actions are not mediated by direct effects of EP4R in VSMCs, but may involve EP4R in endothelium, brain, or kidney epithelia.

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.

scholarly journals Brain Prostaglandin D2 Increases Neurogenic Pressor Activity and Mean Arterial Pressure in Angiotensin II-Salt Hypertensive Rats

Hypertension ◽  
2019 ◽  
Vol 74 (6) ◽  
pp. 1499-1506 ◽  
Author(s):  
Ninitha Asirvatham-Jeyaraj ◽  
A. Daniel Jones ◽  
Robert Burnett ◽  
Gregory D. Fink
Keyword(s):  
Cerebrospinal Fluid ◽  
Angiotensin Ii ◽  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Developmental Stage ◽  
Rostral Ventrolateral Medulla ◽  
Ventrolateral Medulla ◽  
Ang Ii ◽  
Salt Hypertension ◽  
Pressor Activity

This study tested whether brain L-PGDS (lipocalin-type prostaglandin [PG] D synthase), through prostanoid signaling, might increase neurogenic pressor activity and thereby cause hypertension. Sprague Dawley rats on high-salt diet received either vehicle or Ang II (angiotensin II) infusion. On day 4, the developmental stage of hypertension, brains from different sets of control and Ang II–treated rats were collected for measuring L-PGDS expression, PGD2 levels, and DP1R (type 1 PGD2 receptor) expression. In a different set of 14-day Ang II-salt–treated rats, mini-osmotic pumps were used to infuse either a nonselective COX (cyclooxygenase) inhibitor ketorolac, L-PGDS inhibitor AT56, or DP1R inhibitor BWA868C to test the role of brain COX-PGD2-DP1R signaling in Ang II-salt hypertension. The acute depressor response to ganglion blockade with hexamethonium was used to quantify neurogenic pressor activity. During the developmental stage of Ang II-salt hypertension, L-PGDS expression was higher in cerebrospinal fluid, and PGD2 levels were increased in the choroid plexus, cerebrospinal fluid, and the cardioregulatory brain region rostral ventrolateral medulla. DP1R expression was decreased in rostral ventrolateral medulla. Both brain COX inhibition with ketorolac and L-PGDS inhibition with AT56 lowered mean arterial pressure by altering neurogenic pressor activity compared with vehicle controls. Blockade of DP1R with BWA868C, however, increased the magnitude of Ang II-salt hypertension and significantly increased neurogenic pressor activity. In summary, we establish that the development of Ang II-salt hypertension requires increased COX- and L-PGDS–derived PGD2 production in the brain, making L-PGDS a possible target for treating neurogenic hypertension.

Vasodepressor action of angiotensin in conscious chickens

1982 ◽  
Vol 243 (3) ◽  
pp. H456-H462 ◽  
Author(s):  
Y. Nakamura ◽  
H. Nishimura ◽  
M. C. Khosla
Keyword(s):  
Blood Pressure ◽  
Pressor Response ◽  
Direct Action ◽  
Angiotensin Receptors ◽  
Ang Ii ◽  
Prostaglandin Synthetase ◽  
Vasopressin Antagonist ◽  
Native Chicken ◽  
Blood Pressure Responses ◽  
Depressor Action

In chronically cannulated conscious chickens, Gallus gallus, native chicken angiotensin II ([Asp1,Val5]ANG II) caused biphasic blood pressure responses, a depressor followed by a pressor response. The pressor response appears to be mediated primarily by catecholamines. The depressor responses increased with increasing doses and were accompanied by tachycardia. The onset of the depressor action of [Asp1,Val5]ANG II (2.49 +/- 0.22 s) was nearly as quick as that of acetylcholine or histamine. Replacement of aspartic acid in position 1 with sarcosine or asparagine reduced both depressor and pressor potencies, whereas there was no difference either in depressor or pressor potencies between [Asp1,Val5] and [Asp1,Ile5]ANG II. The depressor response to [Asp1,Val5]ANG II was not inhibited by atropine, a vasopressin antagonist, prostaglandin synthetase inhibitors, methysergide, or propranolol but was blocked markedly by [Sar1, Ile8]ANG II and partially by [Sar1,Thr8]ANG II. The results suggest that the vasodepressor action of ANG II is mediated by angiotensin receptors and may possibly be a direct action on the vascular smooth muscle.

Median preoptic nucleus ablation does not affect angiotensin II-induced hypertension

1986 ◽  
Vol 251 (1) ◽  
pp. H148-H152
Author(s):  
G. D. Fink ◽  
C. A. Bruner ◽  
M. L. Mangiapane
Keyword(s):  
Angiotensin Ii ◽  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Cardiovascular Responses ◽  
Base Line ◽  
Ang Ii ◽  
Preoptic Nucleus ◽  
Water Excretion ◽  
Median Preoptic Nucleus ◽  
Induced Hypertension

Previous studies implicated the ventral median preoptic nucleus (MNPOv) in cardiovascular responses to circulating and intracerebroventricular angiotensin II (ANG II) and in normal cardiovascular and fluid homoeostasis. In the present experiments, chronically catheterized rats received continuous (24 h/day) intravenous infusions of ANG II (10 ng/min) for 5 days, and changes in mean arterial pressure, heart rate, water intake and urinary electrolyte and water excretion were determined daily. Three groups of rats were compared as follows: 1) sham-operated control rats (n = 12), 2) rats with 20-70% of the MNPOv ablated electrolytically (n = 6), and 3) rats with over 90% of the MNPOv ablated (n = 5). The organum vasculosum of the lamina terminalis was intact in all three groups. Base-line values of all measured variables were identical in the three groups on two control days preceding ANG II infusion and on two recovery days after infusion. During the administration of ANG II for 5 days, mean arterial pressure rose significantly (and similarly) in all three groups of rats; no other variable was significantly affected by ANG II infusion. These results suggest that neural pathways originating in, or passing through, the MNPOv region are not critical in the pathogenesis of ANG II-induced hypertension in the rat.

Central losartan blocks natriuretic, vasopressin, and pressor responses to central hypertonic NaCl in sheep

1998 ◽  
Vol 275 (2) ◽  
pp. R548-R554 ◽  
Author(s):  
Michael L. Mathai ◽  
Mark D. Evered ◽  
Michael J. McKinley
Keyword(s):  
Arterial Pressure ◽  
Hypertonic Saline ◽  
Pressor Response ◽  
Electrolyte Balance ◽  
Neural Pathways ◽  
Intracerebroventricular Administration ◽  
Ang Ii ◽  
Intracerebroventricular Infusion ◽  
The Central Nervous System ◽  
Vasopressin Secretion

This study investigated the effect of intracerebroventricular administration of the angiotensin AT1 receptor antagonist losartan on the natriuresis, pressor effect, and arginine vasopressin (AVP) secretion caused by intracerebroventricular infusion of either ANG II, hypertonic saline, or carbachol. Losartan (1 mg/h) or artificial cerebrospinal fluid (CSF) was infused into the lateral ventricle before, during, and after infusions of either ANG II at 10 μg/h for 1 h, 0.75 mol/l NaCl at 50 μl/min for 20 min, or carbachol at 1.66 μg/min for 15 min. Intracerebroventricular infusions of ANG II, 0.75 mol/l NaCl, or carbachol caused increases in renal Na+ and K+ excretion, arterial pressure, and plasma AVP levels. Increases in arterial pressure, Na+ excretion, and plasma AVP concentration ([AVP]) in response to intracerebroventricular ANG II or intracerebroventricular 0.75 mol/l NaCl were either abolished or attenuated by intracerebroventricular infusion of losartan but not by intracerebroventricular infusion of artificial CSF or intravenous losartan. Intracerebroventricular losartan did not reduce the increase in plasma [AVP] or arterial pressure in response to intracerebroventricular carbachol, but it did attenuate the natriuretic response to intracerebroventricular carbachol. We conclude that an intracerebroventricular dose of losartan (1 mg/h) that inhibits responses to intracerebroventricular ANG II also inhibits vasopressin secretion, natriuresis, and the pressor response to intracerebroventricular hypertonic saline. These results suggest that common neural pathways are involved in the responses induced by intracerebroventricular administration of ANG II and intracerebroventricular hypertonic NaCl. We propose that intracerebroventricular infusion of hypertonic saline activates angiotensinergic pathways in the central nervous system subserving the regulation of fluid and electrolyte balance and arterial pressure in sheep.

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