Determinants of angiotensin II‐induced hypertrophy versus hyperplasia in vascular smooth muscle

Owens, Gary K.

doi:10.1002/ddr.430290203

Cited by 14 publications

(2 citation statements)

References 34 publications

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“…The observation that ACE inhibitors can prevent arteriolopathy is consistent with other studies that suggest that this group of drugs can reduce SMC proliferation and collagen (18,25). Because a low-salt diet will activate the renin-angiotensin system, we also examined the effect of enalapril and losartan on the arteriolopathy induced by oxonic acid in the setting of a normal-salt diet.…”

Section: Discussionsupporting

confidence: 83%

Hyperuricemia induces a primary renal arteriolopathy in rats by a blood pressure-independent mechanism

Mazzali

Kanellis

Han

et al. 2002

American Journal of Physiology-Renal Physiology

726

611

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Hyperuricemia is associated with hypertension and vascular disease, but whether this represents a causal relationship or an epiphenomenon remains unknown. We recently reported a model of mild hyperuricemia in rats that results in increased blood pressure and mild renal fibrosis. In this study, we examined the effect of hyperuricemia on the renal vasculature. Rats fed 2% oxonic acid and a low-salt diet for 7 wk developed mild hyperuricemia (1.8 vs. 1.4 mg/dl, P < 0.05), hypertension [147 vs. 127 mmHg systolic blood pressure (SBP), P < 0.05], and afferent arteriolar thickening, with a 35% increase in medial area ( P < 0.05). Allopurinol or benziodarone prevented the hyperuricemia, hypertension, and arteriolopathy. Hydrochlorothiazide treatment did not prevent the hyperuricemia or arteriolopathy despite controlling blood pressure. In contrast, the arteriolopathy and hypertension were prevented by both enalapril and losartan. Uric acid also directly stimulated vascular smooth muscle cell proliferation in vitro, and this was partially inhibited by losartan. Thus hyperuricemia induces a renal arteriolopathy in rats that is blood pressure independent and involves the renin-angiotensin system.

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Section: Discussionsupporting

confidence: 83%

Hyperuricemia induces a primary renal arteriolopathy in rats by a blood pressure-independent mechanism

Mazzali

Kanellis

Han

et al. 2002

American Journal of Physiology-Renal Physiology

726

611

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“…Long-term effects of vascular injury, such as arteriosclerotic coronary lesions, are associated with MYPT1 phosphorylation and regress when treated with a ROK inhibitor (346). Inhibition of Rho with C3 or ROK with Y-27632 inhibits angiotensin II-induced protein synthesis (432), perhaps indicating usefulness of ROK inhibition for reducing not only blood pressure, but also hypertensive DNA synthesis (340) and vascular remodeling (292). Stimulation of vascular smooth muscle cell migration by thrombin is mediated by RhoA/ROK and is likely to have major pathological significance through its contribution to neointimal thickening by migrated smooth muscle cells (334,339).…”

Section: B Diseases Of Smooth Musclementioning

confidence: 99%

Ca²⁺Sensitivity of Smooth Muscle and Nonmuscle Myosin II: Modulated by G Proteins, Kinases, and Myosin Phosphatase

Somlyo

2003

Physiological Reviews

1,846

2,075

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Ca2+ sensitivity of smooth muscle and nonmuscle myosin II reflects the ratio of activities of myosin light-chain kinase (MLCK) to myosin light-chain phosphatase (MLCP) and is a major, regulated determinant of numerous cellular processes. We conclude that the majority of phenotypes attributed to the monomeric G protein RhoA and mediated by its effector, Rho-kinase (ROK), reflect Ca2+ sensitization: inhibition of myosin II dephosphorylation in the presence of basal (Ca2+ dependent or independent) or increased MLCK activity. We outline the pathway from receptors through trimeric G proteins (Galphaq, Galpha12, Galpha13) to activation, by guanine nucleotide exchange factors (GEFs), from GDP. RhoA. GDI to GTP. RhoA and hence to ROK through a mechanism involving association of GEF, RhoA, and ROK in multimolecular complexes at the lipid cell membrane. Specific domains of GEFs interact with trimeric G proteins, and some GEFs are activated by Tyr kinases whose inhibition can inhibit Rho signaling. Inhibition of MLCP, directly by ROK or by phosphorylation of the phosphatase inhibitor CPI-17, increases phosphorylation of the myosin II regulatory light chain and thus the activity of smooth muscle and nonmuscle actomyosin ATPase and motility. We summarize relevant effects of p21-activated kinase, LIM-kinase, and focal adhesion kinase. Mechanisms of Ca2+ desensitization are outlined with emphasis on the antagonism between cGMP-activated kinase and the RhoA/ROK pathway. We suggest that the RhoA/ROK pathway is constitutively active in a number of organs under physiological conditions; its aberrations play major roles in several disease states, particularly impacting on Ca2+ sensitization of smooth muscle in hypertension and possibly asthma and on cancer neoangiogenesis and cancer progression. It is a potentially important therapeutic target and a subject for translational research.

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A long-term receptor stimulation is requisite for angiotensin II-dependent DNA synthesis in vascular smooth muscle cells from spontaneously hypertensive rats

Itazaki¹,

Hara²,

Itoh³

et al. 1995

European Journal of Pharmacology: Molecular Pharmacology

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Determinants of angiotensin II‐induced hypertrophy versus hyperplasia in vascular smooth muscle

Abstract: There is clear evidence implicating a role for angiotensin II in control of hypertrophic growth of vascular smooth muscle cells in vivo. However, the specific mechanisms whereby angiotensin II influences smooth muscle cell growth have not been defined.

Cited by 14 publications

References 34 publications

Hyperuricemia induces a primary renal arteriolopathy in rats by a blood pressure-independent mechanism

Hyperuricemia induces a primary renal arteriolopathy in rats by a blood pressure-independent mechanism

Ca²⁺Sensitivity of Smooth Muscle and Nonmuscle Myosin II: Modulated by G Proteins, Kinases, and Myosin Phosphatase

A long-term receptor stimulation is requisite for angiotensin II-dependent DNA synthesis in vascular smooth muscle cells from spontaneously hypertensive rats

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Determinants of angiotensin II‐induced hypertrophy versus hyperplasia in vascular smooth muscle

Abstract: There is clear evidence implicating a role for angiotensin II in control of hypertrophic growth of vascular smooth muscle cells in vivo. However, the specific mechanisms whereby angiotensin II influences smooth muscle cell growth have not been defined.

Cited by 14 publications

References 34 publications

Hyperuricemia induces a primary renal arteriolopathy in rats by a blood pressure-independent mechanism

Hyperuricemia induces a primary renal arteriolopathy in rats by a blood pressure-independent mechanism

Ca2+Sensitivity of Smooth Muscle and Nonmuscle Myosin II: Modulated by G Proteins, Kinases, and Myosin Phosphatase

A long-term receptor stimulation is requisite for angiotensin II-dependent DNA synthesis in vascular smooth muscle cells from spontaneously hypertensive rats

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Product

Resources

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Ca²⁺Sensitivity of Smooth Muscle and Nonmuscle Myosin II: Modulated by G Proteins, Kinases, and Myosin Phosphatase