Enhanced Interaction Between Renovascular α
            <sub>2</sub>
            -Adrenoceptors and Angiotensin II Receptors in Genetic Hypertension

Jackson, Edwin K.; Herzer, William A.; Kost, Curtis K.; Vyas, Subhash J.

doi:10.1161/01.hyp.38.3.353

Cited by 18 publications

(20 citation statements)

References 33 publications

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“…Our studies demonstrate that ␣ 2 -adrenoceptors, which can be activated via norepinephrine released from sympathetic nerves or epinephrine and norepinephrine released from the adrenal medulla, enhance Ang II-induced increases in vascular resistance (Jackson et al, 2001;Gao et al, 2003). This interaction may be of particular biological significance because our studies demonstrate that the ability of ␣ 2 -adrenoceptors to enhance Ang II-induced vasoconstriction both in vivo (Jackson et al, 2001) and in vitro (Gao et al, 2003) is much greater in animals with genetic hypertension compared with normotensive animals or animals with nongenetic hypertension.…”

mentioning

confidence: 66%

“…The influence of endogenous catecholamines on ␣ 2 -adrenoceptors was minimized by bilateral adrenalectomy and denervating the left kidney as described previously (Jackson et al, 2001). Adrenal steroids were replaced by infusing at 25 l/min (via the jugular vein catheter) 0.9% saline containing aldosterone (20 ng/min) and hydrocortisone (20 g/min).…”

Section: Methodsmentioning

confidence: 99%

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Mechanism of the Vascular Angiotensin II/α₂-Adrenoceptor Interaction

Jackson

Gao²,

Zhu³

2005

J Pharmacol Exp Ther

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␣ 2 -Adrenoceptors potentiate vascular responses to angiotensin II. The goal of this study was to test the hypothesis that the phospholipase C (PLC)/protein kinase C (PKC)/c-src/phosphatidylinositol 3-kinase (PI3K) pathway contributes to the vascular angiotensin II/␣ 2 -adrenoceptor interaction. In rats in vivo, intrarenal infusions of angiotensin II (10 ng/kg/min) increased renal vascular resistance by 5.8 Ϯ 0.5 units, and this response was enhanced (p Ͻ 0.05) to 9.1 Ϯ 1.2 units by

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mentioning

confidence: 66%

Section: Methodsmentioning

confidence: 99%

Mechanism of the Vascular Angiotensin II/α₂-Adrenoceptor Interaction

Jackson

Gao²,

Zhu³

2005

J Pharmacol Exp Ther

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“…Indeed, our previous studies demonstrate that activating the G i pathway with the ␣ 2 -adrenoceptor agonist UK14,304 potentiates renovascular responses to Ang II but not to the ␣ 1 -adrenoceptor agonist methoxamine in the SHR kidney. 35 …”

Section: Discussionmentioning

confidence: 99%

Pancreatic Polypeptide-Fold Peptide Receptors and Angiotensin II–Induced Renal Vasoconstriction

Dubinion

Zhu

et al. 2006

Hypertension

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Abstract-TheKey Words: receptors Ⅲ neuropeptides Ⅲ peptides Ⅲ hypertension T he renin-angiotensin system (RAS) is essential for the development and maintenance of genetic hypertension in spontaneously hypertensive rats (SHRs). 1,2 Moreover, transplantation studies reveal that, in addition to the RAS, the SHR kidney is pivotal to the pathophysiology of hypertension in the SHR. 3,4 Finally, the renal sympathetic nervous system also appears to importantly contribute to the pathophysiology of hypertension in SHRs. In support of this latter concept, chronic denervation of the SHR kidney both delays the development of hypertension and attenuates the maximum increase in blood pressure in SHR. [5][6][7][8] Thus, there appears to be a coinvolvement of the RAS, the sympathetic nervous system, and the kidney in SHR hypertension.Many studies have been performed in search of a possible explanation for the coinvolvement of the RAS and the kidney in SHR hypertension. In this regard, studies do not support an increased expression of renal angiotensin II (Ang II) receptors 9 or increased levels of circulating 10 or renal 11 Ang II; also, SHRs do not have altered renal Ang II degradation rates. 12 However, SHRs do exhibit increased renovascular responses to Ang II, 13,14 and this appears to be the explanation for the coinvolvement of the RAS and the kidney in SHR hypertension.Our previous research indicates that G i mediates, in part, the enhanced renovascular response to Ang II in SHR. For example, pertussis toxin, an inhibitor of G i , abolishes the increased renovascular response to Ang II in SHR. 15,16 Importantly, activation of renal sympathetic nerves leads to the release of neuropeptide Y (NPY). 17 NPY is an example of a pancreatic polypeptide (PP)-fold peptide, 18 and NPY binds with high affinity to Y 1 , Y 2 ,

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“…Body temperature was maintained at 37°C. The effects of endogenous catecholamines on ␣ 2 -adrenoceptors were reduced by bilateral adrenalectomy and denervating the left kidney, 1 and adrenal steroids were replaced by infusing aldosterone (20 ng/min, Sigma) and hydrocortisone (20 g/min, Sigma) intravenously.…”

Section: Renovascular Responses In Vivomentioning

confidence: 99%

“…1,2 Previous studies suggest that the signal transduction pathway mediating ␣ 2 -adrenoceptor-induced enhancement of Ang II-induced renal vasoconstriction involves coincident signaling (convergence of signaling) at the level of phospholipase C (PLC), followed by activation of protein kinase C (PKC). The evidence for this conclusion is that U73122 (PLC inhibitor) and GF109203X (PKC inhibitor) abrogate ␣ 2 -adrenoceptorinduced enhancement of Ang II-induced renal vasoconstriction.…”

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confidence: 99%

α ₂ -Adrenoceptors Enhance Angiotensin II–Induced Renal Vasoconstriction

et al. 2008

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Abstract-␣ 2 -Adrenoceptors potentiate renal vascular responses to angiotensin II via coincident signaling at phospholipase C. This leads to increased activation of the phospholipase C/protein kinase C/c-src pathway. Studies suggest that c-src activates the reduced nicotinamide-adenine dinucleotide phosphate (NADPH) oxidase/superoxide system, and reactive oxygen species stimulate the RhoA/Rho kinase pathway. Therefore, we hypothesized that NADPH oxidase/superoxide and RhoA/Rho kinase are downstream components of the signal transduction pathway that mediate the interaction between ␣ 2 -adrenoceptors and angiotensin II on renal vascular resistance. In rat kidneys, both in vivo and in vitro, intrarenal infusions of angiotensin II increased renal vascular resistance, and UK14,304 (␣ 2 -adrenoceptor agonist) enhanced this response. Intrarenal Tempol (superoxide dismutase mimetic) or Y27632 (Rho kinase inhibitor) abolished the interaction between UK14,304 and angiotensin II both in vivo and in vitro. The interaction was also blocked by inhibitors of NADPH oxidase (in vivo using chronic gp91ds-tat administration and in vitro with diphenyleneiodonium).In cultured preglomerular vascular smooth muscle cells, UK14,304 enhanced angiotensin II-induced intracellular superoxide (2-hydroxyethidium production) and potentiated activation of RhoA (Western blot of activated RhoA bound to the binding domain of rhotekin). The interaction between angiotensin II and UK14,304 on superoxide generation and RhoA activation was blocked by inhibitors of phospholipase C (U73312), protein kinase C (GF109203X), c-src (PP1), NADPH oxidase (diphenyleneiodonium), or superoxide (Tempol). We conclude that NADPH oxidase/superoxide and RhoA/Rho kinase are involved in the interaction between ␣ 2 -adrenoceptors and angiotensin II on renal vascular resistance by mediating signaling events downstream of the phospholipase C/protein kinase C/c-src pathway. Key Words: phospholipase C Ⅲ protein kinase C Ⅲ c-src Ⅲ NADPH oxidase Ⅲ superoxide Ⅲ RhoA Ⅲ Rho kinase R enal ␣ 2 -adrenoceptors enhance angiotensin (Ang) IIinduced increases in renal vascular resistance (RVR), particularly in animals with genetic hypertension. 1,2 Previous studies suggest that the signal transduction pathway mediating ␣ 2 -adrenoceptor-induced enhancement of Ang II-induced renal vasoconstriction involves coincident signaling (convergence of signaling) at the level of phospholipase C (PLC), followed by activation of protein kinase C (PKC). The evidence for this conclusion is that U73122 (PLC inhibitor) and GF109203X (PKC inhibitor) abrogate ␣ 2 -adrenoceptorinduced enhancement of Ang II-induced renal vasoconstriction. 2,3 Moreover, activation of G i by ␣ 2 -adrenoceptors releases ␤␥ subunits, 4 and stimulation of Ang II type 1 receptors releases ␣ q from Gq. 5 As reviewed by Selbie and Hill, 6 ␤␥ subunits released by Gi-coupled receptors can synergize with ␣ q subunits released by Gq-coupled receptors to a cause a more robust activation of PLC (most likely PLC-␤ isoforms) and its downstre...

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Enhanced Interaction Between Renovascular α ₂ -Adrenoceptors and Angiotensin II Receptors in Genetic Hypertension

Abstract: Abstract-In

Cited by 18 publications

References 33 publications

Mechanism of the Vascular Angiotensin II/α₂-Adrenoceptor Interaction

Mechanism of the Vascular Angiotensin II/α₂-Adrenoceptor Interaction

Pancreatic Polypeptide-Fold Peptide Receptors and Angiotensin II–Induced Renal Vasoconstriction

α ₂ -Adrenoceptors Enhance Angiotensin II–Induced Renal Vasoconstriction

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Enhanced Interaction Between Renovascular α 2 -Adrenoceptors and Angiotensin II Receptors in Genetic Hypertension

Abstract: Abstract-In

Cited by 18 publications

References 33 publications

Mechanism of the Vascular Angiotensin II/α2-Adrenoceptor Interaction

Mechanism of the Vascular Angiotensin II/α2-Adrenoceptor Interaction

Pancreatic Polypeptide-Fold Peptide Receptors and Angiotensin II–Induced Renal Vasoconstriction

α 2 -Adrenoceptors Enhance Angiotensin II–Induced Renal Vasoconstriction

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Product

Resources

About

Enhanced Interaction Between Renovascular α ₂ -Adrenoceptors and Angiotensin II Receptors in Genetic Hypertension

Mechanism of the Vascular Angiotensin II/α₂-Adrenoceptor Interaction

Mechanism of the Vascular Angiotensin II/α₂-Adrenoceptor Interaction

α ₂ -Adrenoceptors Enhance Angiotensin II–Induced Renal Vasoconstriction