Abstract 306: Alamandine but not angiotensin-(1-7) produces cardiovascular effects in the Insular Cortex

Hypertension ◽  
2014 ◽  
Vol 64 (suppl_1) ◽  
Author(s):  
Fernanda R Marins ◽  
Aline C Oliveira ◽  
Fatimunnisa Qadri ◽  
Natalia Alenina ◽  
Michael Bader ◽  
...  
Keyword(s):  
Brain Region ◽  
Insular Cortex ◽  
Cardiovascular Effects ◽  
Endogenous Ligand ◽  
Renal Nerve ◽  
Renal Sympathetic Nerve Activity ◽  
Equimolar Dose ◽  
The Brain ◽  
Renal Sympathetic ◽  
Made In

In the course of experiments aimed to evaluate the immunofluorescence distribution of MrgD receptors we observed the presence of immunoreactivity for the MrgD protein in the Insular Cortex. In order to evaluate the functional significance of this finding, we investigated the cardiovascular effects produced by the endogenous ligand of MrgD, alamandine, in this brain region. Urethane (1.4g/kg) anesthetized rats were instrumented for measurement of MAP, HR and renal sympathetic nerve activity (RSNA). Unilateral microinjection of alamandine (40 pmol/100nl), Angiotensin-(1-7) (40pmol/100nl), Mas/MrgD antagonista D-Pro7-Ang-1-7 (50pmol/100nl), Mas agonist A779 (100 pmol/100nl) or vehicle (0,9% NaCl) were made in different rats (N=4-6 per group) into posterior insular cortex (+1.5mm rostral to the bregma). Microinjection of alamandine in this region produced a long-lasting (> 18 min) increase in MAP (Δ saline= -2±1 vs. alamandine= 12±2 mmHg, p< 0.05) associated to increases in HR (Δ saline= 2±2 vs. alamandine= 35±5 bpm; p< 0.05) and in the amplitude of renal nerve discharges (Δ saline = -2±1 vs. alamandine= 35±5.5 % of the baseline; p< 0.05). Strikingly, an equimolar dose of angiotensin-(1-7) did not produce any change in MAP or HR (Δ MAP=-0.5±0.3 mmHg and +2.7±1.2 bpm, respectively; p> 0.05) and only a slight increase in RSNA (Δ =7.3±3.2 %) . In keeping with this observation the effects of alamandine were not significantly influenced by A-779 (Δ MAP=+13± 2.5 mmHg, Δ HR= +26±3.6 bpm; Δ RSNA = 25± 3.4%) but completely blocked by the Mas/MrgD antagonist D-Pro7-Ang-(1-7) (Δ MAP=+0 ± 1 mmHg Δ HR= +4±2.6 bpm; Δ RSNA = 0.5± 2.2 %). Therefore, we have identified a brain region in which alamandine/MrgD receptors but not Ang-(1-7)/Mas could be involved in the modulation of cardiovascular-related neuronal activity. This observation also suggests that alamandine might possess unique effects unrelated to Ang-(1-7) in the brain.

Alamandine but not angiotensin-(1-7) produces cardiovascular effects at the rostral insular cortex

2021 ◽  
Author(s):  
Fernanda Ribeiro Marins ◽  
Aline Cristina Oliveira ◽  
Fatimunnisa Qadri ◽  
Daisy Motta-Santos ◽  
Natalia Alenina ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Brain Region ◽  
Insular Cortex ◽  
Cardiovascular Effects ◽  
Endogenous Ligand ◽  
Renal Sympathetic Nerve Activity ◽  
G Protein Coupled ◽  
The Brain ◽  
Renal Sympathetic ◽  
Made In

Experiments aimed to evaluate the tissue distribution of Mas-related G-protein coupled receptor D (MrgD) revealed the presence of immunoreactivity for the MrgD protein in the rostral insular cortex (rIC), an important area for autonomic and cardiovascular control. In order to investigate the relevance of this finding, we evaluated the cardiovascular effects produced by the endogenous ligand of MrgD, alamandine, in this brain region. Mean arterial pressure (MAP), heart rate (HR) and renal sympathetic nerve activity (RSNA) were recorded in urethane anesthetized rats. Unilateral microinjection of equimolar doses of alamandine (40pmol/100nl), angiotensin-(1-7), angiotensin II, angiotensin A and Mas/MrgD antagonist D-Pro7-Ang-1-7 (50pmol/100nl), Mas antagonist A779 (100pmol/100nl) or vehicle (0.9% NaCl) were made in different rats (N=4-6 per group) into rIC. To verify the specificity of the region, a microinjection of alamandine was also performed into intermediate insular cortex (iIC). Microinjection of alamandine in rIC produced an increase in MAP (Δ=15±2mmHg), HR (Δ=36±4bpm) and RSNA (Δ=31±4%), but was without effects at iIC. Strikingly, an equimolar dose of angiotensin-(1-7) at rIC did not produce any change in MAP, HR and RSNA. Angiotensin II and angiotensin A produced only minor effects. Alamandine effects were not altered by A-779, a Mas antagonist, but were completely blocked by the Mas/MrgD antagonist D-Pro7-Ang-(1-7). Therefore, we have identified a brain region in which alamandine/MrgD receptor but not angiotensin-(1-7)/Mas could be involved in the modulation of cardiovascular-related neuronal activity. This observation also suggests that alamandine might possess unique effects unrelated to angiotensin-(1-7) in the brain.

Reflex effects on components of synchronized renal sympathetic nerve activity

1998 ◽  
Vol 275 (3) ◽  
pp. F441-F446 ◽  
Author(s):  
Gerald F. DiBona ◽  
Susan Y. Jones
Keyword(s):  
Sympathetic Nerve ◽  
Peak Frequency ◽  
Peak Height ◽  
Nerve Fibers ◽  
Receptor Stimulation ◽  
Renal Nerve ◽  
Renal Sympathetic Nerve Activity ◽  
Renal Sympathetic Nerve ◽  
Baroreceptor Stimulation ◽  
Renal Sympathetic

The effects of peripheral thermal receptor stimulation (tail in hot water, n = 8, anesthetized) and cardiac baroreceptor stimulation (volume loading, n = 8, conscious) on components of synchronized renal sympathetic nerve activity (RSNA) were examined in rats. The peak height and peak frequency of synchronized RSNA were determined. The renal sympathoexcitatory response to peripheral thermal receptor stimulation was associated with an increase in the peak height. The renal sympathoinhibitory response to cardiac baroreceptor stimulation was associated with a decrease in the peak height. Although heart rate was significantly increased with peripheral thermal receptor stimulation and significantly decreased with cardiac baroreceptor stimulation, peak frequency was unchanged. As peak height reflects the number of active fibers, reflex increases and decreases in synchronized RSNA are mediated by parallel increases and decreases in the number of active renal nerve fibers rather than changes in the centrally based rhythm or peak frequency. The increase in the number of active renal nerve fibers produced by peripheral thermal receptor stimulation reflects the engagement of a unique group of silent renal sympathetic nerve fibers with a characteristic response pattern to stimulation of arterial baroreceptors, peripheral and central chemoreceptors, and peripheral thermal receptors.

Renal sympathetic nerve activity modulates afferent renal nerve activity by PGE2-dependent activation of α1- and α2-adrenoceptors on renal sensory nerve fibers

2007 ◽  
Vol 293 (4) ◽  
pp. R1561-R1572 ◽  
Author(s):  
Ulla C. Kopp ◽  
Michael Z. Cicha ◽  
Lori A. Smith ◽  
Jan Mulder ◽  
Tomas Hökfelt
Keyword(s):  
Sensory Nerve ◽  
Nerve Fibers ◽  
Sensory Nerves ◽  
Nerve Activity ◽  
Renal Nerve ◽  
Renal Sympathetic Nerve Activity ◽  
Pelvic Wall ◽  
Renal Nerve Activity ◽  
Pelvic Perfusion ◽  
Renal Sympathetic

Increasing efferent renal sympathetic nerve activity (ERSNA) increases afferent renal nerve activity (ARNA). To test whether the ERSNA-induced increases in ARNA involved norepinephrine activating α-adrenoceptors on the renal sensory nerves, we examined the effects of renal pelvic administration of the α1- and α2-adrenoceptor antagonists prazosin and rauwolscine on the ARNA responses to reflex increases in ERSNA (placing the rat's tail in 49°C water) and renal pelvic perfusion with norepinephrine in anesthetized rats. Hot tail increased ERSNA and ARNA, 6,930 ± 900 and 4,870 ± 670%·s (area under the curve ARNA vs. time). Renal pelvic perfusion with norepinephrine increased ARNA 1,870 ± 210%·s. Immunohistochemical studies showed that the sympathetic and sensory nerves were closely related in the pelvic wall. Renal pelvic perfusion with prazosin blocked and rauwolscine enhanced the ARNA responses to reflex increases in ERSNA and norepinephrine. Studies in a denervated renal pelvic wall preparation showed that norepinephrine increased substance P release, from 8 ± 1 to 16 ± 1 pg/min, and PGE2 release, from 77 ± 11 to 161 ± 23 pg/min, suggesting a role for PGE2 in the norepinephrine-induced activation of renal sensory nerves. Prazosin and indomethacin reduced and rauwolscine enhanced the norepinephrine-induced increases in substance P and PGE2. PGE2 enhanced the norepinephrine-induced activation of renal sensory nerves by stimulation of EP4 receptors. Interaction between ERSNA and ARNA is modulated by norepinephrine, which increases and decreases the activation of the renal sensory nerves by stimulating α1- and α2-adrenoceptors, respectively, on the renal pelvic sensory nerve fibers. Norepinephrine-induced activation of the sensory nerves is dependent on renal pelvic synthesis/release of PGE2.

The actions of Shiga toxin-2 administration into the brain on renal sympathetic nerve activity

2011 ◽  
Vol 16 (3) ◽  
pp. 382-388 ◽  
Author(s):  
Akio Nakamura ◽  
Akira Imaizumi ◽  
Takao Kohsaka ◽  
Chunlong Huang ◽  
Chunhua Huang ◽  
...  
Keyword(s):  
Shiga Toxin ◽  
Sympathetic Nerve ◽  
Sympathetic Nerve Activity ◽  
Nerve Activity ◽  
Renal Sympathetic Nerve Activity ◽  
Renal Sympathetic Nerve ◽  
Shiga Toxin 2 ◽  
The Brain ◽  
Renal Sympathetic

Aging is not accompanied by sympathetic hyperresponsiveness to air-jet stress

1996 ◽  
Vol 271 (2) ◽  
pp. H768-H775 ◽  
Author(s):  
H. M. Stauss ◽  
D. A. Morgan ◽  
K. E. Anderson ◽  
M. P. Massett ◽  
K. C. Kregel
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Low Frequency ◽  
Nerve Activity ◽  
Renal Nerve ◽  
Renal Sympathetic Nerve Activity ◽  
Fischer 344 ◽  
Air Jet ◽  
Renal Nerve Activity ◽  
Renal Sympathetic

It has been postulated that sympathetic nervous system reactivity to acutely applied stress is increased with age. We investigated the autonomic and hemodynamic adjustments to air-jet stress in 9 mature (12-mo-old) and 11 senescent (24-mo-old) Fischer 344 rats. Rats were instrumented with arterial and venous catheters, flow probes around the renal artery, and nerve electrodes on the ipsilateral renal nerve. After the rats recovered from surgery, blood pressure, heart rate, renal blood flow, and renal sympathetic nerve activity were recorded during control conditions and during an 8-min continuous air-jet application. Renal resistance and the low (0.01-0.20 Hz)- and mid-frequency (0.20-0.50 Hz) power of blood pressure were computed off-line. The air jet induced an increase in blood pressure, heart rate, renal resistance, renal nerve activity, and blood pressure power in the low- and mid-frequency ranges in both groups. Blood pressure and low-frequency blood pressure power increased less, and the elevations in renal resistance and renal nerve activity were of shorter duration in senescent compared with mature rats. These data suggest that sympathetic responsiveness to air-jet stress is not enhanced with increasing age.

IL (Interleukin)-17A Acts in the Brain to Drive Neuroinflammation, Sympathetic Activation, and Hypertension

Hypertension ◽  
2021 ◽  
Vol 78 (5) ◽  
pp. 1450-1462
Author(s):  
Yiling Cao ◽  
Yang Yu ◽  
Baojian Xue ◽  
Ye Wang ◽  
Xiaolei Chen ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Intravenous Injection ◽  
Sympathetic Nerve ◽  
Sympathetic Nerve Activity ◽  
Nerve Activity ◽  
Renal Sympathetic Nerve Activity ◽  
Renal Sympathetic Nerve ◽  
The Brain ◽  
Renal Sympathetic

IL (Interleukin)-17A is a key inflammatory mediator contributing to chronic tissue inflammation. The present study sought to determine whether IL-17A plays a role in regulating neuroinflammation, hemodynamics, and sympathetic outflow in normal and hypertensive animals. In urethane-anesthetized rats, intravenous injection of IL-17A induced dramatic and prolonged increases in blood pressure, heart rate, and renal sympathetic nerve activity, which were significantly attenuated by an IL-17RA (IL-17 receptor A) siRNA in the hypothalamic paraventricular nucleus (PVN). Either intracerebroventricular or PVN microinjection of IL-17A also elicited a similar excitatory response in blood pressure, heart rate, and renal sympathetic nerve activity. Intravenous injection of IL-17A upregulated the mRNA level of IL-17A, IL-17F, and IL-17RA in the PVN. Additionally, intravenous injection of IL-17A activated brain-resident glial cells and elevated the gene expression of inflammatory cytokines and chemokines in the PVN, which were markedly diminished by PVN microinjection of IL-17RA siRNA. Pretreatments with microglia or astrocyte inhibitors attenuated the increase in blood pressure, heart rate, and renal sympathetic nerve activity in response to PVN IL-17A. Moreover, intracerebroventricular injection of IL-17A activated TGF (transforming growth factor)-β activated kinase 1, p44/42 mitogen-activated protein kinase, and transcriptional nuclear factor κB in the PVN. IL-17A interacted with tumor necrosis factor-α or IL-1β synergistically to exaggerate its influence on hemodynamic and sympathetic responses. Central intervention suppressing IL-17RA in the PVN significantly reduced angiotensin II–induced hypertension, neuroinflammation, and sympathetic tone in the rats. Collectively, these data indicated that IL-17A in the brain promotes neuroinflammation to advance sympathetic activation and hypertension, probably by a synergistic mechanism involving the interaction with various inflammatory mediators within the brain.

Abstract 080: Selective Knockout of the Intracellular Isoform of Renin in the Brain Contributes to Metabolic and Cardiovascular Control

Hypertension ◽  
2014 ◽  
Vol 64 (suppl_1) ◽  
Author(s):  
Keisuke Shinohara ◽  
Matthew D Folchert ◽  
Benjamin J Weidemann ◽  
Xuebo Liu ◽  
Donald A Morgan ◽  
...  
Keyword(s):  
Resting Metabolic Rate ◽  
Total Body Weight ◽  
Cardiovascular Control ◽  
Pcr Analysis ◽  
Functional Link ◽  
Renal Sympathetic Nerve Activity ◽  
Renin Gene ◽  
Total Body ◽  
The Brain ◽  
Renal Sympathetic

Renin gene expression is regulated by two distinct promoter-first exon combinations that target renin for either secretion (exon 1a initiating secreted renin, sREN) or for cytoplasmic retention (exon 1b initiating intracellular renin, icREN). The icREN isoform is expressed predominantly in the brain and its expression is downregulated whereas sREN expression is upregulated by deoxycorticosterone (DOCA)-salt suggesting each isoform may be differentially regulated. We generated mice that lack icREN, but preserve sREN, by flanking exon-1b and its surrounding sequences (including the promoter) with loxP sites and breeding successively with mice expressing flipase and cre-recombinase. Real time quantitative RT-PCR analysis revealed a loss of icREN mRNA in the brain, but a preservation of sREN mRNA in the kidney. Total body weight was normal in male icREN-KO mice (26.3±0.7 g, n=8, 12 wk) compared to controls (25.3±0.7 g, n=12, 12 wk), but total (2.14±0.09 g vs 2.46±0.11 g) and relative (9.0±0.5 % vs 10.7±0.6%) fat mass as measured by NMR were reduced in 8-week icREN-KO mice (n=14-16, P<0.05). Whereas food intake was normal, there was an increase in resting metabolic rate as measured by respirometry in icREN-KO (0.1484±0.0036 kcal/hr, n=41, P=0.02 by ANCOVA) vs controls (0.1389±0.0038 kcal/hr, n=38). There was also a trend toward decreased digestive efficiency (81.1±1.0%, n=6, P=0.06) vs controls (84.9±1.2%, n=3) at 22 wk of age. Systolic blood pressure was decreased in icREN-KO mice (113±1 mmHg, n=12, 17.0±1.2 wk vs 120±3 mmHg, n=5, 15.9±1.9 wk, P<0.05). We previously reported a functional link between the synthesis and action of angiotensin-II and the action of leptin. We tested if this was impaired in icREN-KO mice by measuring the renal sympathetic nerve activity (RSNA) response to acute intracerebroventricular (ICV) administration of leptin. The decrease in arterial pressure was confirmed in this cohort of icREN-KO mice. Surprisingly, the RSNA response to leptin was greater in icREN-KO mice compared to controls (257.9±16.0%, n=3 vs 157.0±13.9%, n=4, 4 hr after leptin, P=0.01). Captopril attenuated the sympathetic response to ICV leptin. Together these data suggest that this novel icREN isoform contributes to metabolic and cardiovascular control.

Partial renal ischemia elicits heterogeneous control of renal sympathetic nerve activity to ischemic and nonischemic regions of the kidney

2006 ◽  
Vol 290 (2) ◽  
pp. R322-R330 ◽  
Author(s):  
Kiyoshi Shimizu ◽  
Kanji Matsukawa ◽  
Jun Murata ◽  
Hirotsugu Tsuchimochi ◽  
Ishio Ninomiya
Keyword(s):  
Sympathetic Nerve ◽  
Sympathetic Nerve Activity ◽  
Renal Ischemia ◽  
Nerve Activity ◽  
Renal Nerve ◽  
Renal Sympathetic Nerve Activity ◽  
Renal Sympathetic Nerve ◽  
Ischemic Region ◽  
Nerve Bundles ◽  
Renal Sympathetic

We tested the hypothesis that renal sympathetic nerve activity (RSNA) to the ischemic and nonischemic regions responded differently during partial ischemia of the kidney in pentobarbital-anesthetized cats. The renal artery divides into two branches at the front of the renal hilus: one branch perfuses predominantly the dorsal half of the kidney, and the other perfuses its ventral half. We identified the innervated area of a renal nerve bundle by supramaximal electrical stimulation and subsequently determined the changes in RSNA in response to occlusion of either renal arterial branch for 3 min. RSNA to the nonischemic region of the kidney gradually decreased by 23 ± 4% during partial renal ischemia, whereas RSNA to the ischemic region of the same kidney showed no significant change. Crushing either all renal nerve bundles or only the renal nerve bundles terminated to the ischemic region abolished the decrease in RSNA to the nonischemic region. Furthermore, intra-arterial administration of a prostaglandin synthesis inhibitor (meclofenamate, 4 mg/kg) abolished the decrease in RSNA to the nonischemic region of the kidney. Following spinal transection at the level of T7, the inhibitory response in RSNA to the nonischemic region disappeared, whereas the RSNA to the ischemic region was markedly augmented by 47 ± 17%. Thus it is likely that renal chemoreceptors activated during renal partial ischemia elicit heterogeneous control of renal sympathetic outflows to the ischemic and nonischemic regions of the same kidney, which may be determined by a net output between the supraspinal inhibitory and spinal excitatory reflexes.

scholarly journals EP3 receptors mediate PGE2-induced hypothalamic paraventricular nucleus excitation and sympathetic activation

2011 ◽  
Vol 301 (4) ◽  
pp. H1559-H1569 ◽  
Author(s):  
Zhi-Hua Zhang ◽  
Yang Yu ◽  
Shun-Guang Wei ◽  
Yoshiko Nakamura ◽  
Kazuhiro Nakamura ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Paraventricular Nucleus ◽  
Hypothalamic Paraventricular Nucleus ◽  
Prostaglandin E ◽  
Renal Sympathetic Nerve Activity ◽  
Ep Receptors ◽  
Ep Receptor ◽  
Immunohistochemical Studies ◽  
The Brain ◽  
Renal Sympathetic

Prostaglandin E2 (PGE2), an important mediator of the inflammatory response, acts centrally to elicit sympathetic excitation. PGE2 acts on at least four E-class prostanoid (EP) receptors known as EP1, EP2, EP3, and EP4. Since PGE2 production within the brain is ubiquitous, the different functions of PGE2 depend on the expression of these prostanoid receptors in specific brain areas. The type(s) and location(s) of the EP receptors that mediate sympathetic responses to central PGE2 remain unknown. We examined this question using PGE2, the relatively selective EP receptor agonists misoprostol and sulprostone, and the available selective antagonists for EP1, EP3, and EP4. In urethane-anesthetized rats, intracerebroventricular (ICV) administration of PGE2, sulprostone or misoprostol increased renal sympathetic nerve activity, blood pressure, and heart rate. These responses were significantly reduced by ICV pretreatment with the EP3 receptor antagonist; the EP1 and EP4 receptor antagonists had little or no effect. ICV PGE2 or misoprostol increased the discharge of neurons in the hypothalamic paraventricular nucleus (PVN). ICV misoprostol increased the c-Fos immunoreactivity of PVN neurons, an effect that was substantially reduced by the EP3 receptor antagonist. Real-time PCR detected EP3 receptor mRNA in PVN, and immunohistochemical studies revealed sparsely distributed EP3 receptors localized in GABAergic terminals and on a few PVN neurons. Direct bilateral PVN microinjections of PGE2 or sulprostone elicited sympathoexcitatory responses that were significantly reduced by the EP3 receptor antagonist. These data suggest that EP3 receptors mediate the central excitatory effects of PGE2 on PVN neurons and sympathetic discharge.

Glutamatergic input in the PVN is important in renal nerve response to elevations in osmolality

2003 ◽  
Vol 285 (4) ◽  
pp. F640-F650 ◽  
Author(s):  
Emilio Badoer ◽  
Chi-Wai Ng ◽  
Robert De Matteo
Keyword(s):  
Hypertonic Saline ◽  
Sympathetic Nerve Activity ◽  
Plasma Osmolality ◽  
Neural Responses ◽  
Neuronal Function ◽  
Renal Nerve ◽  
Renal Sympathetic Nerve Activity ◽  
Nerve Response ◽  
Humoral Responses ◽  
Renal Sympathetic

Elevations in plasma osmolality elicit reflex humoral and neural responses. The hypothalamic paraventricular nucleus (PVN) is important in humoral responses. We have investigated whether the PVN contributed to the renal nerve reduction that is normally elicited by increased plasma osmolality in the conscious rabbit. Renal sympathetic nerve activity (RSNA) was monitored after an intravenous infusion of hypertonic saline (1.7 M NaCl, 2 ml/min for 7 min). The responses were examined in animals microinjected with muscimol (10 nmol) into, and outside, the PVN to acutely inhibit neuronal function or with kynurenate (25 nmol) to block glutamate receptors. Compared with vehicle, the maximum reduction in RSNA elicited by hypertonic saline was significantly less with muscimol or kynurenate pretreatment into the PVN. A similar study with kynurenate was also performed in sinoaortically denervated rabbits, and similar effects were observed. The effect was specific to the PVN because microinjections of the drugs outside the PVN had no effect on the response. The findings suggest that excitatory inputs into the PVN may be important in the neural responses elicited by elevations in plasma osmolality.

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