Role of periaqueductal gray in the pressor response produced by central injections of angiotensin II

1993 ◽  
Vol 265 (5) ◽  
pp. R1052-R1059
Author(s):  
L. R. Portis ◽  
S. J. Lewis ◽  
M. J. Brody
Keyword(s):  
Electrical Stimulation ◽  
Angiotensin Ii ◽  
Fluorescent Dyes ◽  
Pressor Response ◽  
Periaqueductal Gray ◽  
Ang Ii ◽  
Hemodynamic Responses ◽  
Anesthetized Rats ◽  
Stimulation Of

The present studies were undertaken to determine the role of rostral periaqueductal gray (PAG) in mediating the pressor effect produced by intracerebroventricular (icv) injection of angiotensin II (ANG II, 200 ng). Two functionally and anatomically distinct sites were identified in rostral PAG: a dorsomedial site involved in the hemodynamic responses produced by electrical stimulation of the anteroventral third ventricle (AV3V) region and a ventromedial site required for the pressor response elicited by icv administration of ANG II. In Saffan-anesthetized rats, injection of lidocaine (LIDO, 4%) in dorsomedial PAG, but not in ventromedial PAG, significantly attenuated the decrease in hindquarter resistance (HQR) produced by electrical stimulation of the AV3V region, and the poststimulatory increase in mean arterial pressure (MAP) and HQR. The injection of LIDO in ventromedial PAG had no effect on the hemodynamic responses produced by electrical stimulation of the AV3V region in anesthetized rats but significantly attenuated the pressor response produced by icv administration of ANG II in conscious rats. The hypothesis that these two sites receive separate projections was addressed by microinjecting two retrogradely transported fluorescent dyes, Fluoro-Gold and Fast Blue. The anatomic findings suggest that separation of the pathways activated by electrical and chemical stimulation of the AV3V region occurs at the level of rostral PAG.

Reactive Oxygen Species-Mediated Homologous Downregulation of Angiotensin II Type 1 Receptor Mrna by Angiotensin II

Hypertension ◽  
2000 ◽  
Vol 36 (suppl_1) ◽  
pp. 688-688
Author(s):  
Toshihiro Ichiki ◽  
Kotaro Takeda ◽  
Akira Takeshita
Keyword(s):  
Reactive Oxygen Species ◽  
Angiotensin Ii ◽  
Nadph Oxidase ◽  
Mrna Expression ◽  
Crucial Role ◽  
Oxygen Species ◽  
Ang Ii ◽  
Stimulation Of

58 Recent studies suggest a crucial role of reactive oxygen species (ROS) for the signaling of Angiotensin II (Ang II) through type 1 Ang II receptor (AT1-R). However, the role of ROS in the regulation of AT1-R expression has not been explored. In this study, we examined the effect of an antioxidant on the homologous downregulation of AT1-R by Ang II. Ang II (10 -6 mol/L) decreased AT1-R mRNA with a peak suppression at 6 hours of stimulation in rat aortic vascular smooth muscle cells (VSMC). Ang II dose-dependently (10 -8 -10 -6 ) suppressed AT1-R mRNA at 6 hours of stimulation. Preincubation of VSMC with N-acetylcysteine (NAC), a potent antioxidant, almost completely inhibited the Ang II-induced downregulation of AT1-R mRNA. The effect of NAC was due to stabilization of the AT1-R mRNA that was destabilized by Ang II. Ang II did not affect the promoter activity of AT1-R gene. Diphenylene iodonium (DPI), an inhibitor of NADH/NADPH oxidase failed to inhibit the Ang II-induced AT1-R mRNA downregulation. The Ang II-induced AT1-R mRNA downregulation was also blocked by PD98059, an extracellular signal-regulated protein kinase (ERK) kinase inhibitor. Ang II-induced ERK activation was inhibited by NAC as well as PD98059 whereas DPI did not inhibit it. To confirm the role of ROS in the regulation of AT1-R mRNA expression, VSMC were stimulated with H 2 O 2 . H 2 O 2 suppressed the AT1-R mRNA expression and activated ERK. These results suggest that production of ROS and activation of ERK are critical for downregulation of AT1-R mRNA. The differential effect of NAC and DPI on the downregulation of AT1-R mRNA may suggest the presence of other sources than NADH/NADPH oxidase pathway for ROS in Ang II signaling. Generation of ROS through stimulation of AT1-R not only mediates signaling of Ang II but may play a crucial role in the adaptation process of AT1-R to the sustained stimulation of Ang II.

scholarly journals Mechanisms of angiotensin II stimulation of NCC are time-dependent in mDCT15 cells

2015 ◽  
Vol 308 (7) ◽  
pp. F720-F727 ◽  
Author(s):  
Benjamin Ko ◽  
Abinash Mistry ◽  
Lauren Hanson ◽  
Rickta Mallick ◽  
Robert S. Hoover
Keyword(s):  
Angiotensin Ii ◽  
Cell Model ◽  
Surface Protein ◽  
Early Time ◽  
Dependent Manner ◽  
Ang Ii ◽  
Biphasic Effect ◽  
Surface Protein Expression ◽  
Stimulation Of

Angiotensin II (ANG II) increases thiazide-sensitive sodium-chloride cotransporter (NCC) activity both acutely and chronically. ANG II has been implicated as a switch that turns WNK4 from an inhibitor of NCC into an activator of NCC, and ANG II's effect on NCC appears to require WNK4. Chronically, ANG II stimulation of NCC results in an increase in total and phosphorylated NCC, but the role of NCC phosphorylation in acute ANG II actions is unclear. Here, using a mammalian cell model with robust native NCC activity, we corroborate the role that ANG II plays in WNK4 regulation and clarify the role of Ste20-related proline alanine-rich kinase (SPAK)-induced NCC phosphorylation in ANG II action. ANG II was noted to have a biphasic effect on NCC, with a peak increase in NCC activity in the physiologic range of 10−11 M ANG II. This effect was apparent as early as 15 min and remained sustained through 120 min. These changes correlated with significant increases in NCC surface protein expression. Knockdown of WNK4 expression sharply attenuated the effect of ANG II. SPAK knockdown did not affect ANG II action at early time points (15 and 30 min), but it did attenuate the response at 60 min. Correspondingly, NCC phosphorylation did not increase at 15 or 30 min, but increased significantly at 60 min. We therefore conclude that within minutes of an increase in ANG II, NCC is rapidly trafficked to the cell surface in a phosphorylation-independent but WNK4-dependent manner. Then, after 60 min, ANG II induces SPAK-dependent phosphorylation of NCC.

Role of calcium in osmotic and nonosmotic release of vasopressin from rat organ culture

1983 ◽  
Vol 244 (5) ◽  
pp. R703-R708
Author(s):  
S. Ishikawa ◽  
R. W. Schrier
Keyword(s):  
Angiotensin Ii ◽  
Organ Culture ◽  
Arginine Vasopressin ◽  
Ionophore A23187 ◽  
Ang Ii ◽  
Ca Uptake ◽  
High Concentrations ◽  
Cellular Ca ◽  
Stimulation Of

In the present study the role of calcium (Ca) in the stimulation of arginine vasopressin (AVP) release from the cultured rat hypothalamoneurohypophyseal complex (HNC) was examined in response to three different stimuli, 56 mM potassium chloride, an increase in medium osmolality from 290 to 310 mosmol/kg H2O, or 1 X 10(-6) M angiotensin II (ANG II). With all three stimuli AVP release from rat HNC explants was enhanced by increasing Ca concentration in the medium from 0 to 1.8 mM Ca. However, high concentrations of Ca (8 mM) inhibited the response of AVP release to either hyperosmolality or angiotensin II. Chemically dissimilar blockers of cellular Ca uptake, verapamil (5.2 X 10(-6) or 5.2 X 10(-5) M) or nifedipine (5.8 X 10(-6) or 5.8 X 10(-5) M), completely abolished AVP release from rat HNC explants in response to the three different stimuli in 1.8 mM Ca. In a normal concentration of medium Ca (1.8 mM) a Ca ionophore, A23187 (3.8 X 10(-5) M), significantly enhanced the osmotic and nonosmotic (ANG II-stimulated) release of AVP from rat HNC explants compared with controls without Ca ionophore. This effect of Ca ionophore to enhance AVP release was more evident in a lower Ca medium (0.9 mM Ca in the hyperosmolality study and 0.3 mM Ca in the ANG II study). These results therefore indicate that cellular Ca uptake is an important modulator of osmotic and nonosmotic AVP release from the intact rat hypothalamoneurohypophyseal system. The influence of extracellular Ca on the osmotic and nonosmotic release of AVP is also demonstrated.

Role of endogenous angiotensin II on sympathetic reflexes in conscious rabbits

1997 ◽  
Vol 272 (6) ◽  
pp. R1816-R1825 ◽  
Author(s):  
R. D. Bendle ◽  
S. C. Malpas ◽  
G. A. Head
Keyword(s):  
Angiotensin Ii ◽  
Pressor Response ◽  
Ang Ii ◽  
At1 Antagonist ◽  
Before And After ◽  
Sympathetic Reflexes ◽  
Conscious Rabbits ◽  
Dose Dependent ◽  
Renal Sympathetic

In the present study we sought to determine the contribution of endogenous brain stem angiotensin to renal sympathetic reflexes in conscious rabbits. Initial studies determined the subtype of receptor involved in the pressor response to angiotensin II (ANG II) administration into the fourth ventricle (4V). The AT1 antagonist losartan (0.001-10 micrograms 4V) had no effect on blood pressure alone but caused a dose-dependent blockade of the pressor effect of ANG II, with complete blockade produced by 10 micrograms, an effect that lasted for at least 3 h. The AT2 antagonist PD-123319 (0.1-1,000 micrograms) and vehicle had no effect on the ANG II pressor response. The effect of losartan (10 micrograms) on the baroreceptor, chemoreceptor, and trigeminal reflexes was examined in eight rabbits that had been implanted with 4V catheters and an electrode for recording renal sympathetic nerve activity (RSNA) 1 wk earlier. Baroreflex assessments were made during normoxia and two conditions of hypoxia (10% O2 and 10% O2 + 3% CO2) before and after 10 micrograms losartan or vehicle, on separate experimental days. During normoxia and hypoxia+CO2 losartan increased resting RSNA, the range, and upper plateau of the RSNA-MAP baroreflex curves. By contrast the marked increase in RSNA due to activation of trigeminal afferents was not affected by losartan. In conclusion the effect of losartan to increase RSNA activity in conscious rabbits, particularly during hypoxia and baroreceptor unloading, suggests that endogenous ANG II via AT1 receptors normally inhibits renal sympathetic baroreceptor and chemoreceptor reflexes.

Abstract 610: Context-Dependent Effects of Suppressor of Cytokine Signaling 3 (SOCS3) in Angiotensin II-Induced Vascular Dysfunction: Mechanisms and Role of Bone Marrow-Derived Cells

Hypertension ◽  
2014 ◽  
Vol 64 (suppl_1) ◽  
Author(s):  
Ying Li ◽  
Dale Kinzenbaw ◽  
Mary Modrick ◽  
Lecia Epping ◽  
John T Harty ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Angiotensin Ii ◽  
Endothelial Dysfunction ◽  
Vascular Disease ◽  
Vascular Dysfunction ◽  
Pressor Response ◽  
Ang Ii ◽  
Bone Marrow Derived Cells ◽  
The Impact

Angiotensin II (Ang II) promotes vascular disease and hypertension, in part, by activating the interleukin-6 (IL-6)/signal transducer and activator of transcription 3 (STAT3) pathway. Although SOCS3 regulates this pathway in the immune system, its role in vascular disease and hypertension is unknown. In this study, we investigated the role of SOCS3 in a model of Ang II-induced vascular disease. To exam direct effects, carotid arteries from wild-type (WT) and SOCS3 haplodeficient (SOCS3 +/- ) mice were incubated with Ang II for 22 hrs, followed by examination of endothelial function using acetylcholine (Ach). Relaxation to Ach was similar in all arteries incubated with vehicle. A low concentration of Ang II (1 nmol/L) did not affect Ach-induced vasodilation in WT mice, but reduced that of SOCS3 +/- mice by ~50% (P<0.05). Ang II-induced impairment was prevented by inhibitors of STAT3, IL-6, NF-κB, or a scavenger of superoxide. Responses to nitroprusside were similar in all groups. We also tested the impact of SOCS3 in vivo by systemically infusing Ang II (1.4 mg/kg per day) for 14 days via osmotic mini-pumps. Ach-induced vasodilation in carotid and resistance arteries in brain from WT mice was reduced by ~60% (P<0.05). Surprisingly, deficiency in SOCS3 prevented the majority of Ang II-induced endothelial dysfunction without affecting the pressor response to Ang II. Lethally irradiated WT mice reconstituted with SOCS3 +/- bone marrow were protected from Ang II-induced endothelial dysfunction (P<0.05), while reconstitution of irradiated SOCS3 +/- mice with WT bone marrow exacerbated Ang II-induced vascular dysfunction (P<0.05). WT into WT and SOCS3 +/- into SOCS3 +/- bone marrow chimeras exhibited vascular function consistent with non-irradiated controls. The pressor response to Ang II was reduced by ~50% in WT mice reconstituted with bone marrow from SOCS3 +/- mice (P<0.05). These data suggest SOCS3 exerts divergent local versus systemic effects on Ang II-induced vascular dysfunction. In the face of SOCS3 deficiency, bone marrow-derived cells protect against Ang II-induced vascular dysfunction and hypertension.

scholarly journals Evidence for a role of nitric oxide in hindlimb vasodilation induced by hypothalamic stimulation in anesthetized rats

2005 ◽  
Vol 77 (2) ◽  
pp. 245-257 ◽  
Author(s):  
Marcos L. Ferreira-Neto ◽  
Olga S. Possas ◽  
Oswaldo U. Lopes ◽  
Sérgio L. Cravo
Keyword(s):  
Nitric Oxide ◽  
Electrical Stimulation ◽  
Adrenergic Receptors ◽  
Hypothalamic Stimulation ◽  
Bilateral Adrenalectomy ◽  
Alpha Adrenoceptor ◽  
Anesthetized Rats ◽  
Nos Inhibitor ◽  
Stimulation Of

Electrical stimulation of the hypothalamus produces cardiovascular adjustments consisting of hypertension, tachycardia, visceral vasoconstriction and hindlimb vasodilation. Previous studies have demonstrated that hindlimb vasodilation is due a reduction of sympathetic vasoconstrictor tone and to activation of beta2-adrenergic receptors by catecholamine release. However, the existence of a yet unidentified vasodilator mechanism has also been proposed. Recent studies have suggested that nitric oxide (NO) may be involved. The aim of the present study was to investigate the role of NO in the hindquarter vasodilation in response to hypothalamic stimulation. In pentobarbital-anesthetized rats hypothalamic stimulation (100 Hz, 150µA, 6 s) produced hypertension, tachycardia, hindquarter vasodilation and mesenteric vasoconstriction. Alpha-adrenoceptor blockade with phentolamine (1.5 mg/kg, iv) plus bilateral adrenalectomy did not modify hypertension, tachycardia or mesenteric vasoconstriction induced by hypothalamic stimulation. Hindquarter vasodilation was strongly reduced but not abolished. The remaining vasodilation was completely abolished after iv injection of the NOS inhibitor L-NAME (20 mg/kg, iv). To properly evaluate the role of the mechanism of NO in hindquarter vasodilation, in a second group of animals L-NAME was administered before alpha-adrenoceptor blockade plus adrenalectomy. L-NAME treatment strongly reduced hindquarter vasodilation in magnitude and duration. These results suggest that NO is involved in the hindquarter vasodilation produced by hypothalamic stimulation.

Role of vasopressin in stimulation of ACTH secretion by angiotensin II in conscious dogs

1986 ◽  
Vol 251 (1) ◽  
pp. E52-E57
Author(s):  
C. K. Klingbeil ◽  
L. C. Keil ◽  
D. Chang ◽  
I. A. Reid
Keyword(s):  
Angiotensin Ii ◽  
Arginine Vasopressin ◽  
Water Deprivation ◽  
Conscious Dogs ◽  
Ang Ii ◽  
Acth Secretion ◽  
Series Of Experiments ◽  
Stimulation Of ◽  
Acth Release

Three series of experiments were performed in conscious dogs to test the possibility that the stimulation of adrenocorticotropin (ACTH) release by angiotensin II (ANG II) is mediated by arginine vasopressin (AVP). In the first protocol, the effect of ANG II on ACTH release was studied in dogs in which endogenous AVP levels had been increased by water deprivation. Water deprivation for 24 h increased plasma AVP concentration from 3.0 +/- 0.5 to 7.7 +/- 0.5 pg/ml (P less than 0.01) and increased the AVP response to the highest dose of ANG II (20 ng X kg-1 X min-1). Despite these changes, water deprivation failed to increase the ACTH response to ANG II. Next, the contribution of endogenous AVP to the stimulation of ACTH release by ANG II was examined using the V1-receptor antagonist, d(CH2)5Tyr[Met]-AVP (10 micrograms/kg iv). The ACTH response to ANG II in the presence of the AVP antagonist (66.4 +/- 3.1 to 100.1 +/- 15.9 pg/ml) was not significantly less than that in its absence (53.0 +/- 4.8 to 72.2 +/- 11.1 pg/ml). Finally, ANG II and AVP were infused in combination to determine whether there is a synergism between these two peptides in the release of ACTH. In one protocol, AVP and ANG II were infused separately and in combination. The ACTH response to ANG II and AVP in combination (48.7 +/- 6.5 to 61.5 +/- 8.5 pg/ml) was not enhanced compared with the responses to ANG II (59.8 +/- 7.3 to 71.0 +/- 10.1 pg/ml) or AVP (48.8 +/- 5.7 to 55.6 +/- 6.5 pg/ml) alone.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Role of Chemoreceptor Activation in Hemodynamic Responses to Electrical Stimulation of the Carotid Sinus in Conscious Rats

Hypertension ◽  
2015 ◽  
Vol 66 (3) ◽  
pp. 598-603 ◽  
Author(s):  
Pedro L. Katayama ◽  
Jaci A. Castania ◽  
Daniel P.M. Dias ◽  
Kaushik P. Patel ◽  
Rubens Fazan ◽  
...  
Keyword(s):  
Electrical Stimulation ◽  
Carotid Sinus ◽  
Hemodynamic Responses ◽  
Conscious Rats ◽  
Stimulation Of
Sign in / Sign up

Export Citation Format

Share Document