Role of Renal Sympathetic Nerves in Regulating Renovascular Responses to Angiotensin II in Spontaneously Hypertensive Rats

Dubinion, John H.; Mi, Zaichuan; Jackson, Edwin K.

doi:10.1124/jpet.106.101279

Cited by 19 publications

(16 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Increased systemic and renal vascular sensitivity to ANG II is observed in normotensive men with a family history of HTN (187), and in SHR even in the developmental phase of HTN (21,180). Also, sympathetic nerves enhance the renovascular responses to ANG II in SHR (34). The ability of PGI 2 to attenuate ANG II-induced vasoconstriction is also reduced in the kidney of SHR (72).…”

Section: Renal Endothelial Cell Dysfunction In Htnmentioning

confidence: 86%

Cellular mediators of renal vascular dysfunction in hypertension

Ponnuchamy¹,

Khalil²

2009

American Journal of Physiology-Regulatory, Integrative and Comp

View full text Add to dashboard Cite

Ponnuchamy B, Khalil RA. Cellular mediators of renal vascular dysfunction in hypertension. Am J Physiol Regul Integr Comp Physiol 296: R1001-R1018, 2009. First published February 18, 2009 doi:10.1152/ajpregu.90960.2008.-The renal vasculature plays a major role in the regulation of renal blood flow and the ability of the kidney to control the plasma volume and blood pressure. Renal vascular dysfunction is associated with renal vasoconstriction, decreased renal blood flow, and consequent increase in plasma volume and has been demonstrated in several forms of hypertension (HTN), including genetic and salt-sensitive HTN. Several predisposing factors and cellular mediators have been implicated, but the relationship between their actions on the renal vasculature and the consequent effects on renal tubular function in the setting of HTN is not clearly defined. Gene mutations/ defects in an ion channel, a membrane ion transporter, and/or a regulatory enzyme in the nephron and renal vasculature may be a primary cause of renal vascular dysfunction. Environmental risk factors, such as high dietary salt intake, vascular inflammation, and oxidative stress further promote renal vascular dysfunction. Renal endothelial cell dysfunction is manifested as a decrease in the release of vasodilatory mediators, such as nitric oxide, prostacyclin, and hyperpolarizing factors, and/or an increase in vasoconstrictive mediators, such as endothelin, angiotensin II, and thromboxane A 2. Also, an increase in the amount/activity of intracellular Ca 2ϩ concentration, protein kinase C, Rho kinase, and mitogenactivated protein kinase in vascular smooth muscle promotes renal vasoconstriction. Matrix metalloproteinases and their inhibitors could also modify the composition of the extracellular matrix and lead to renal vascular remodeling. Synergistic interactions between the genetic and environmental risk factors on the cellular mediators of renal vascular dysfunction cause persistent renal vasoconstriction, increased renal vascular resistance, and decreased renal blood flow, and, consequently, lead to a disturbance in the renal control mechanisms of water and electrolyte balance, increased plasma volume, and HTN. Targeting the underlying genetic defects, environmental risk factors, and the aberrant renal vascular mediators involved should provide complementary strategies in the management of HTN. blood pressure; dietary salt; oxidative stress; cytokines; kidney; endothelium; vascular smooth muscle; extracellular matrix; matrix metalloproteinases THE ROLE OF THE KIDNEY IN the regulation of sodium and water balance and blood pressure (BP) is well recognized (53,55,128). A decrease in plasma volume and renal blood flow (RBF) stimulates renin release from the juxtaglomerular cells (JGCs) and activates the renin-angiotensin system (RAS). Renin transforms angiotensinogen to angiotensin I (ANG I), and angiotensin-converting enzyme (ACE) transforms ANG I to ANG II. ANG II stimulates the adrenal cortex to release aldosterone (Aldo), which acts on the rena...

show abstract

Section: Renal Endothelial Cell Dysfunction In Htnmentioning

confidence: 86%

Cellular mediators of renal vascular dysfunction in hypertension

Ponnuchamy¹,

Khalil²

2009

American Journal of Physiology-Regulatory, Integrative and Comp

View full text Add to dashboard Cite

show abstract

“…In spontaneously hypertensive rats, which display an increased density of periarterial NPY-containing but not CGRP-containing nerves (Gradin et al, 2003;Luff et al, 2005), BIBP3226 does not lower blood pressure even during stress-induced stimulation of the sympathetic nervous system (Zhao et al, 1997). However, in this model BIBP3226 displays an age-dependent reducing effect on the enhanced neurogenic renovascular constriction (Vonend et al, 2005;Dubinion et al, 2006). A role for endogenous CGRP herein has not been considered yet.…”

Section: Efs (2 N Hzmentioning

confidence: 92%

Functional Antagonism between Endogenous Neuropeptide Y and Calcitonin Gene-Related Peptide in Mesenteric Resistance Arteries

Mey¹,

Megens²,

Fazzi³

2007

J Pharmacol Exp Ther

View full text Add to dashboard Cite

To test the hypothesis that endogenous neuropeptide Y (NPY) counteracts the vasodilator effects of calcitonin gene-related peptide (CGRP), we used isolated mesenteric resistance arteries of rats and mice. With immunohistochemistry, we observed CGRP-containing fibers along and in the vicinity of a subset of NPY-or tyrosine hydroxylase-immunoreactive fibers. The CGRP1 receptor component calcitonin-related-like receptor was expressed by periarterial nerves and smooth muscle cells, whereas receptor activity-modifying protein 1 was observed primarily on the smooth muscle. In organ chambers, exogenous CGRP caused relaxations that were reversed by exogenous NPY. The effects were inhibited by 1-piperidinecarboxamide, N-[2-[[5-amino-1-[[4-(4-pyridinyl) NPY increased contractile responses to K ϩ and BIBP3226 (400 nM) reduced contractile responses to EFS. These effects were inhibited by capsaicin and BIBN4096BS, respectively. Furthermore, the relaxing effect of exogenous CGRP (10 nM) during phenylephrine-induced contraction (30 M) was reversed by EFS, and this effect was reduced in the presence of BIBP3226. We confirmed that bioactive concentrations of endogenous CGRP and NPY can be released from periarterial sensory-motor and sympathetic nerves, respectively, and we demonstrate for the first time functional antagonism between endogenous NPY and CGRP at the level of the smooth muscle.The potent 37-amino acid vasodilator calcitonin-gene related peptide (CGRP) can be released by perivascular sensory-motor nerves (for review, see Brain and Grant, 2004). CGRP contributes to cardiovascular homeostasis in the fetus (Thakor and Giussani, 2005) and to the cardiovascular adaptations to pregnancy (Yallampalli et al., 2002). It lowers blood pressure and reduces end-organ damage in several experimental models (Deng and Li, 2005;Supowit et al., 2005; Márquez-Rodas et al., 2006). In experimental hypertension, changes in the expression and effects of CGRP either contribute to the increase in blood pressure or they play a compensatory role (Wang and Wang, 2004;Deng and Li, 2005;Supowit et al., 2005; Márquez-Rodas et al., 2006). Interventions that increase the efficacy of the vasodilator effects of endogenous CGRP could thus be a welcome addition to antihypertensive therapy. Enzymatic breakdown of CGRP (Fernandez-Patron et al., 2000), the density of CGRP-containing nerve fibers (Kawasaki et al., 1999), and the expression of CGRP receptor components (Zhang et al., 2006) are subjects of ongoing research. We hypothesize that effects of CGRP are modulated by other neuropeptides.During development, afferent sensory-motor nerves and efferent postganglionic sympathetic nerves align with outgrowing arteries (for review, see Carmeliet and TessierLavigne, 2005). This suggests that depending on their sensiThis study was supported by grants from the Transnational University of Limburg and contract T2-108 from TIPharma (Leiden, The Netherlands), an initiative financed by the Dutch government that encourages collaborative pharmacological rese...

show abstract

“…The present study does not examine the interaction between NPY 14 Thus, with respect to the interaction between Ang II and NPY , it is a moot point as to whether DPP IV regulates the levels of NPY in WKY kidneys because the peptide cannot significantly alter Ang II-induced renal vasoconstriction regardless of whether or not it is metabolized by DPP IV. The ability of Y 1 Rs to enhance renovascular responses in SHR kidneys, but not WKY kidneys, is attributable to the fact that Y 1 Rs signal via the Gi pathway.…”

Section: Discussionmentioning

confidence: 99%

Sitagliptin Augments Sympathetic Enhancement of the Renovascular Effects of Angiotensin II in Genetic Hypertension

Jackson

2008

Hypertension

Self Cite

View full text Add to dashboard Cite

Abstract-DipeptidylIn this regard, there are 2 endogenous agonists of Y 1 Rs that would be presented to the kidney microcirculation, ie, peptide YY 1-36 (PYY ) and neuropeptide Y 1-36 (NPY 1-36 ). Both are pancreatic polypeptide-fold peptides. A fatty meal releases PYY 1-36 into the systemic circulation from endocrine L-cells in the small bowel, colon, and rectum producing physiologically active levels of PYY in plasma that are 500% to 1000% above basal circulating levels, 2-8 and this circulating PYY 1-36 would be delivered promptly to the renal microcirculation via the blood stream (humoral Y 1 R-agonist input to kidney microcirculation). Renal sympathetic nerves release NPY 1-36 in response to central nervous system-mediated activation of the renal sympathetic nerves (neural Y 1 Ragonist input to kidney microcirculation), resulting in high local levels of NPY 1-36 in sympathetically-innervated renal microvessels during renal sympathetic activation. 9 Because both PYY 1-36 and NPY 1-36 are potent Y 1 R agonists, 10,11 physiological processes that increase PYY 1-36 release from the gut, NPY 1-36 release from renal sympathetic nerves, or both simultaneously would activate Y 1 Rs in the renal microcirculation, which in genetically-susceptible kidneys would enhance Ang II-induced renal vasoconstriction.

show abstract

Role of Renal Sympathetic Nerves in Regulating Renovascular Responses to Angiotensin II in Spontaneously Hypertensive Rats

Cited by 19 publications

References 32 publications

Cellular mediators of renal vascular dysfunction in hypertension

Cellular mediators of renal vascular dysfunction in hypertension

Functional Antagonism between Endogenous Neuropeptide Y and Calcitonin Gene-Related Peptide in Mesenteric Resistance Arteries

Sitagliptin Augments Sympathetic Enhancement of the Renovascular Effects of Angiotensin II in Genetic Hypertension

Contact Info

Product

Resources

About