scholarly journals Inhibitory effects of angiotensin-(1–7) on the nerve stimulation-induced release of norepinephrine and neuropeptide Y from the mesenteric arterial bed

2010 ◽  
Vol 298 (2) ◽  
pp. H457-H465 ◽  
Author(s):  
Mirnela Byku ◽  
Heather Macarthur ◽  
Thomas C. Westfall
Keyword(s):  
Neuropeptide Y ◽  
Receptor Antagonist ◽  
Renin Angiotensin System ◽  
Sympathetic Nerves ◽  
Ang Ii ◽  
Spontaneously Hypertensive ◽  
Angiotensin Type 2 Receptor ◽  
Mesenteric Arterial Bed ◽  
Wistar Kyoto

Neuropeptide Y (NPY) is a cotransmitter with norepinephrine (NE) and ATP in sympathetic nerves. There is evidence for increased activity of the sympathetic nervous system and the renin-angiotensin system (RAS), as well as a role for NPY in the development of hypertension in experimental animal models and in humans. Angiotensin II (ANG II) is known to facilitate sympathetic neurotransmission, an effect greater in spontaneously hypertensive rats (SHR) than normotensive Wistar-Kyoto (WKY) rats. A newly discovered product of the RAS is angiotensin-(1–7) [ANG-(1–7)]. There is evidence suggesting that ANG-(1–7) opposes the actions of ANG II, resulting in hypotensive effects. The objective of this study was to investigate the role of ANG-(1–7) on the nerve-stimulated overflow of NE and NPY from the mesenteric arterial bed of SHR and the mechanisms involved in mediating any effects produced. ANG-(1–7) (0.001, 0.01, 0.1 μM) decreased nerve-stimulated NE and NPY overflow, as well as perfusion pressure in preparations obtained from SHR. This effect was greater in preparations of SHR than WKY controls. In addition, ANG-(1–7) decreased NE overflow to a greater extent than NPY overflow. Administration of the Mas receptor antagonist, d-Ala7 ANG-(1–7), attenuated the decrease in both NE and NPY overflow due to ANG-(1–7) administration. However, the angiotensin type 2 receptor antagonist, PD-123391, attenuated the effect of ANG-(1–7) on NE overflow without affecting the decrease in NPY overflow. Moreover, in the presence of NG-nitro-l-arginine methyl ester, ANG-(1–7) decreased NPY overflow, but not NE overflow. ANG-(1–7) decreases the nerve-stimulated overflow of NE and NPY in preparations of SHR, whereas ANG II enhances it. Therefore, ANG-(1–7) may counteract the effects of ANG II by acting on ANG type 2 and Mas receptors.

scholarly journals Nerve stimulation induced overflow of neuropeptide Y and modulation by angiotensin II in spontaneously hypertensive rats

2008 ◽  
Vol 295 (5) ◽  
pp. H2188-H2197 ◽  
Author(s):  
Mirnela Byku ◽  
Heather Macarthur ◽  
Thomas C. Westfall
Keyword(s):  
Neuropeptide Y ◽  
Receptor Antagonist ◽  
Nerve Stimulation ◽  
Renin Angiotensin System ◽  
Ang Ii ◽  
Angiotensin System ◽  
Spontaneously Hypertensive ◽  
Renin Angiotensin ◽  
Wky Rats ◽  
Angiotensin Type 2 Receptor

The sympathetic nervous system and renin-angiotensin system are both thought to contribute to the development and maintenance of hypertension in experimental models such as the spontaneously hypertensive rat (SHR). We demonstrated that periarterial nerve stimulation (NS) increased the perfusion pressure (PP) and neuropeptide Y (NPY) overflow from perfused mesenteric arterial beds of SHRs at 4–6, 10–12, and 18–20 wk of age, which correspond to prehypertensive, developing hypertensive, and maintained hypertensive stages, respectively, in the SHR. NS also increased PP and NPY overflow from mesenteric beds of Wistar-Kyoto (WKY) normotensive rats. NS-induced increases in PP and NPY were greater in vessels obtained from SHRs of all three ages compared with WKY rats. ANG II produced a greater increase in PP in preparations taken from SHRs than WKY rats. ANG II also resulted in a greater increase in basal NPY overflow from 10- to 12-wk-old and 18- to 20-wk-old SHRs than age-matched WKY rats. ANG II enhanced the NS-induced overflow of NPY from SHR preparations more than WKY controls at all ages studied. The enhancement of NS-induced NPY overflow by ANG II was blocked by the AT1 receptor antagonist EMD-66684 and the angiotensin type 2 receptor antagonist PD-123319. In contrast, ANG II greatly enhanced norepinephrine overflow in the presence of PD-123319. Both captopril and EMD-66684 decreased neurotransmitter overflow from SHR mesenteric beds; therefore, we conclude that an endogenous renin-angiotensin system is active in this preparation. It is concluded that the ANG II-induced enhancement of sympathetic nerve stimulation may contribute to the development and maintenance of hypertension in the SHR.

scholarly journals NPY1–36 and PYY1–36 activate cardiac fibroblasts: an effect enhanced by genetic hypertension and inhibition of dipeptidyl peptidase 4

2015 ◽  
Vol 309 (9) ◽  
pp. H1528-H1542 ◽  
Author(s):  
Xiao Zhu ◽  
Delbert G. Gillespie ◽  
Edwin K. Jackson
Keyword(s):  
Peptide Yy ◽  
Cardiac Fibroblasts ◽  
Sympathetic Nerves ◽  
Dipeptidyl Peptidase ◽  
Ang Ii ◽  
Collagen Production ◽  
Spontaneously Hypertensive ◽  
Dipeptidyl Peptidase 4 ◽  
Genetic Hypertension ◽  
Wistar Kyoto

Cardiac sympathetic nerves release neuropeptide Y (NPY)1–36, and peptide YY (PYY)1–36 is a circulating peptide; therefore, these PP-fold peptides could affect cardiac fibroblasts (CFs). We examined the effects of NPY1–36 and PYY1–36 on the proliferation of and collagen production ([3H]proline incorporation) by CFs isolated from Wistar-Kyoto (WKY) normotensive rats and spontaneously hypertensive rats (SHRs). Experiments were performed with and without sitagliptin, an inhibitor of dipeptidyl peptidase 4 [DPP4; an ectoenzyme that metabolizes NPY1–36 and PYY1–36 (Y1 receptor agonists) to NPY3–36 and PYY3–36 (inactive at Y1 receptors), respectively]. NPY1–36 and PYY1–36, but not NPY3–36 or PYY3–36, stimulated proliferation of CFs, and these effects were more potent than ANG II, enhanced by sitagliptin, blocked by BIBP3226 (Y1 receptor antagonist), and greater in SHR CFs. SHR CF membranes expressed more receptor for activated C kinase (RACK)1 [which scaffolds the Gi/phospholipase C (PLC)/PKC pathway] compared with WKY CF membranes. RACK1 knockdown (short hairpin RNA) and inhibition of Gi (pertussis toxin), PLC (U73122), and PKC (GF109203X) blocked the proliferative effects of NPY1–36. NPY1–36 and PYY1–36 stimulated collagen production more potently than did ANG II, and this was enhanced by sitagliptin and greater in SHR CFs. In conclusion, 1) NPY1–36 and PYY1–36, via the Y1 receptor/Gi/PLC/PKC pathway, activate CFs, and this pathway is enhanced in SHR CFs due to increased localization of RACK1 in membranes; and 2) DPP4 inhibition enhances the effects of NPY1–36 and PYY1–36 on CFs, likely by inhibiting the metabolism of NPY1–36 and PYY1–36. The implications are that endogenous NPY1–36 and PYY1–36 could adversely affect cardiac structure/function by activating CFs, and this may be exacerbated in genetic hypertension and by DPP4 inhibitors.

Angiotensin II acts at AT1receptors in the nucleus of the solitary tract to attenuate the baroreceptor reflex

1998 ◽  
Vol 275 (5) ◽  
pp. R1611-R1619 ◽  
Author(s):  
Kiyoshi Matsumura ◽  
David B. Averill ◽  
Carlos M. Ferrario
Keyword(s):  
Arterial Pressure ◽  
Receptor Antagonist ◽  
Baroreceptor Reflex ◽  
Ang Ii ◽  
Solitary Tract ◽  
Spontaneously Hypertensive ◽  
Wky Rats ◽  
Reflex Control ◽  
Wistar Kyoto ◽  
Baroreceptor Reflex Control

The object of the current study was to determine if ANG II acts at type 1 (AT1) or type 2 (AT2) receptors in the nucleus of the solitary tract (NTS) to reduce baroreceptor reflex control of renal sympathetic nerve activity (RSNA) and heart rate (HR). Experiments were carried out in urethan-anesthetized Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). Reflex changes in RSNA and HR were elicited by intravenous infusion of either phenylephrine or sodium nitroprusside before and after bilateral microinjection of CV-11974 (AT1 receptor antagonist, 10 pmol), PD-123319 (AT2 receptor antagonist, 100 pmol), or artificial cerebrospinal fluid (aCSF, 50 nl) in the NTS. Mean arterial pressure (MAP)-RSNA and MAP-HR data were fit to logistic functions to analyze the baroreceptor reflex. Baroreceptor reflex sensitivities for RSNA and HR were attenuated in SHR compared with those in WKY rats. Bilateral injection of CV-11974, PD-123319, or aCSF in the NTS of either strain had no effect on baseline arterial pressure, HR, or RSNA. However, CV-11974 injected in the NTS increased significantly ( P < 0.01) the sensitivities for baroreceptor reflex control of RSNA and HR in SHR and WKY rats. Neither PD-123319 nor aCSF altered baroreceptor reflex control of RSNA and HR in either SHR or WKY rats. These results demonstrate that endogenous ANG II acts at AT1 receptors of the NTS to attenuate the baroreceptor reflex in SHR as well as in WKY rats.

Angiotensin II receptors are expressed and functional in human esophageal mucosa

2009 ◽  
Vol 297 (5) ◽  
pp. G1019-G1027 ◽  
Author(s):  
Anna Casselbrant ◽  
Anders Edebo ◽  
Peter Hallersund ◽  
Emma Spak ◽  
Herbert F. Helander ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Ion Transport ◽  
Receptor Antagonist ◽  
Ussing Chamber ◽  
Renin Angiotensin System ◽  
Esophageal Mucosa ◽  
Ang Ii

Only few studies have been devoted to the actions of the renin-angiotensin system (RAS) in the human gastrointestinal tract. The present study was undertaken to elucidate the expression and action of RAS in the human esophageal mucosa. Mucosal specimens with normal histological appearance were obtained from healthy subjects undergoing endoscopy and from patients undergoing esophagectomy due to neoplasm. Gene and protein expressions of angiotensin II (Ang II) receptor type 1 (AT1) and type 2 (AT2) and angiotensin-converting enzyme (ACE) were analyzed. In vivo functionality in healthy volunteers was reflected by assessing transmucosal potential difference (PD). Ussing chamber technique was used to analyze the different effects of Ang II on its AT1 and AT2 receptors. Immunoreactivity to AT1 and AT2 was localized to stratum superficiale and spinosum in the epithelium. ACE, AT1, and AT2 were found in blood vessel walls. Transmucosal PD in vivo increased following administration of the AT1 receptor antagonist candesartan. In Ussing preparations mean basal transmural PD was −6.4 mV, epithelial current ( Iep) 34 μA/cm2, and epithelial resistance ( Rep) 321 Ω·cm2. Serosal exposure to Ang II increased PD as a result of increased Iep, whereas Rep was constant. Ang II given together with the selective AT1-receptor antagonist losartan, or AT2 agonist C21 given alone, resulted in a similar effect. Ang II given in presence of the AT2-receptor antagonist PD123319 did not influence PD, but Iep decreased and Rep increased. In conclusion, Ang II receptors and ACE are expressed in the human esophageal epithelium. The results suggest that AT2-receptor stimulation increases epithelial ion transport, whereas the AT1 receptor inhibits ion transport and increases Rep.

scholarly journals Dieckol Reduces Muscle Atrophy by Modulating Angiotensin Type II Type 1 Receptor and NADPH Oxidase in Spontaneously Hypertensive Rats

Antioxidants ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 1561
Author(s):  
Seyeon Oh ◽  
Jin Young Yang ◽  
Chul Hyun Park ◽  
Kuk Hui Son ◽  
Kyunghee Byun
Keyword(s):  
Muscle Atrophy ◽  
Renin Angiotensin System ◽  
Serum Levels ◽  
Treg Cells ◽  
Ang Ii ◽  
Hypertensive Rats ◽  
Cross Sectional ◽  
Spontaneously Hypertensive ◽  
Wistar Kyoto

The renin–angiotensin system is involved in the development of hypertension and sarcopenia. Increased levels of angiotensin II (Ang II) lead to upregulation of Ang II type 1 receptor (AT1R), which results in increasing reactive oxygen species (ROS) by NAD(P)H oxidase (Nox). Increased ROS led to increased helper T17 (Th17) and decreased regulatory T (Treg) cells through HIF-1α. Increased Th17 secretes more IL-17, leading to increased NF-κB and muscle atrophy. We evaluated the effect of Ecklonia cava extracts (ECE) and dieckol (DK) on attenuating muscle atrophy by decreasing AT1R and NOX activity in spontaneous hypertensive rats (SHRs). The serum levels of Ang II and expression of AT1R in the muscle were higher in SHRs than in normotensive animals of Wistar–Kyoto rats (2.4 and 1.8 times higher than WKY, respectively). The expression of AT1R decreased by ECE or DK (0.62 and 0.84 times lower than SHR, respectively). In SHRs, the expression of Nox 1, 2, and 4 were increased (1.2–1.15 times higher than WKY) but were decreased by the administration of ECE (0.8–0.9 times lower than SHR) or DK (0.7–0.9 times lower than SHR). The Nox activity was increased in SHRs (2.3 times more than WKY) and it was decreased by ECE (0.9 times lower than SHRs) and DK (0.9 times lower than SHRs). The expression of HIF-1α, a marker of Th17 (RORγt), and cytokine secreted by Th17 (IL-17) was increased in SHRs and was decreased by ECE or DK. The marker of Treg (Foxp3) and cytokine secreted from Treg cells (IL-10) was decreased in SHRs and was increased by ECE or DK. The expression of NF-κB/IL-1β/TNF-α and MuRF-1/MAFbx/atrogin-1 was increased in SHRs and these were decreased by ECE or DK. The cross-sectional area of muscle fiber was decreased in SHRs (0.7 times lower than WKY) and was increased by ECE (1.3 times greater than SHR) or DK (1.5 times greater than SHR). In conclusion, ECE or DK leads to a decreased expression of AT1R and Nox activity which modulates Th17/Treg balance and consequently, decreased muscle atrophy.

scholarly journals Primacy of angiotensin converting enzyme in angiotensin-(1–12) metabolism

2013 ◽  
Vol 305 (5) ◽  
pp. H644-H650 ◽  
Author(s):  
Norihito Moniwa ◽  
Jasmina Varagic ◽  
Stephen W. Simington ◽  
Sarfaraz Ahmad ◽  
Sayaka Nagata ◽  
...  
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Renin Angiotensin System ◽  
Ang Ii ◽  
Converting Enzyme ◽  
Hypertensive Rats ◽  
Angiotensin System ◽  
Spontaneously Hypertensive ◽  
Angiotensin Peptides ◽  
Wistar Kyoto

Angiotensin-(1–12) [ANG-(1–12)], a new member of the renin-angiotensin system, is recognized as a renin independent precursor for ANG II. However, the processing of ANG-(1–12) in the circulation in vivo is not fully established. We examined the effect of angiotensin converting enzyme (ACE) and chymase inhibition on angiotensin peptides formation during an intravenous infusion of ANG-(1–12) in normotensive Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). WKY and SHR were assigned to a short ANG-(1–12) infusion lasting 5, 15, 30, or 60 min ( n = 4–10 each group). In another experiment WKY and SHR were assigned to a continuous 15-min ANG-(1–12) infusion with pretreatment of saline, lisinopril (10 mg/kg), or chymostatin (10 mg/kg) ( n = 7–13 each group). Saline or lisinopril were infused intravenously 15 min before the administration of ANG-(1–12) (2 nmol·kg−1·min−1), whereas chymostatin was given by bolus intraperitoneal injection 30 min before ANG-(1–12). Infusion of ANG-(1–12) increased arterial pressure and plasma ANG-(1–12), ANG I, ANG II, and ANG-(1–7) levels in WKY and SHR. Pretreatment with lisinopril caused increase in ANG-(1–12) and ANG I and large decreases in ANG II compared with the other two groups in both strains. Pretreatment of chymostatin had no effect on ANG-(1–12), ANG I, and ANG II levels in both strains, whereas it increased ANG-(1–7) levels in WKY. We conclude that ACE acts as the primary enzyme for the conversion of ANG-(1–12) to smaller angiotensin peptides in the circulation of WKY and SHR and that chymase may be an ANG-(1–7) degrading enzyme.

Effects of dietary salt changes on renal renin-angiotensin system in rats

2002 ◽  
Vol 283 (5) ◽  
pp. F995-F1002 ◽  
Author(s):  
Catherine Ingert ◽  
Michèle Grima ◽  
Catherine Coquard ◽  
Mariette Barthelmebs ◽  
Jean-Louis Imbs
Keyword(s):  
Renal Cortex ◽  
Salt Content ◽  
Renin Angiotensin System ◽  
Fold Increase ◽  
Kidney Cortex ◽  
Ang Ii ◽  
Dietary Salt ◽  
High Sodium ◽  
Ace Activity ◽  
Wistar Kyoto

Renin (RA) and angiotensin-converting enzyme (ACE) activities and angiotensinogen, ANG I, and ANG II levels were measured in the kidney (cortex and medulla) and plasma of Wistar-Kyoto rats on a low-sodium (LS; 0.025% NaCl; n= 8), normal-sodium (NS; 1% NaCl; n = 7), or high-sodium (HS; 8% NaCl; n = 7) diet for 21 days. RA, ANG I, and ANG II levels increased in a manner inversely related to sodium content of the diet in both plasma and renal tissues. The LS diet resulted in a 16-, 2.8-, and 1.8-fold increase in plasma RA, ANG I, and ANG II levels, respectively, compared with those in HS rats. In the renal cortex and medulla, RA, ANG I, and ANG II levels were also increased by diminution of dietary salt content but, in contrast to plasma, ANG II levels increased much more than RA or ANG I levels [5.4 (cortex)- and 4.7 (medulla)-fold compared with HS rats]. In summary, we demonstrated variations of ANG II levels in the kidney during dietary salt modifications. Our results confirm that RA and ACE activity are not the steps limiting intrarenal ANG II levels. Nevertheless, despite RA and ACE activity differences between renal cortex and medulla, ANG I and ANG II levels are equivalent in these two tissues; these results argue against a compartmentalization of RAS in these two intrarenal areas.

Renal cytochrome P-450-arachidonic acid metabolism: localization and hormonal regulation in SHR

1992 ◽  
Vol 262 (4) ◽  
pp. F591-F599 ◽  
Author(s):  
K. Omata ◽  
N. G. Abraham ◽  
M. L. Schwartzman
Keyword(s):  
Hormonal Regulation ◽  
Distribution Patterns ◽  
Arachidonic Acid Metabolism ◽  
Proximal Tubules ◽  
Ang Ii ◽  
Spontaneously Hypertensive ◽  
Nephron Segments ◽  
Wistar Kyoto ◽  
Cytochrome P 450 ◽  
Stimulation Of

Epoxygenase and omega- and omega-1-hydroxylases are the major cytochrome P-450-arachidonate (P-450-AA) metabolizing enzymes in renal tissues. We measured P-450-AA metabolism in single nephron segments and determined the tubular localization of this activity in spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). Formation of 20-hydroxyeicosatetraenoic acid (20-HETE), the product of AA omega-hydroxylase was specifically localized in the entire proximal tubules (S1, S2, and S3 segments), whereas formation of 19-HETE, the product of omega-1-hydroxylase and epoxyeicosatrienoic acids (EETs), products of AA epoxygenase, was demonstrable throughout the tubule. Although distribution patterns were similar in SHR and WKY, formation of 19- and 20-HETE in the proximal tubules was higher in SHR, whereas the formation of EETs was not different between the two strains. In the proximal tubules, angiotensin II (ANG II) significantly stimulated epoxygenase activity (EETs formation), whereas parathyroid hormone (PTH) and epidermal growth factor (EGF) had no effect on epoxygenase but significantly stimulated omega-hydroxylase activity (20-HETE formation). Because P-450-AA metabolites have a wide and contrasting spectrum of biological and renal effects, from vasodilation to vasoconstriction and from inhibition to stimulation of Na(+)-K(+)-adenosinetriphosphatase, their localization to the specific nephron segments and differential stimulation of their formation by ANG II, PTH, and EGF may contribute not only to renal hemodynamics and blood pressure regulation but also to the regulation of renal sodium and water balance.

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