Localization of the Renin–Angiotensin System Components to the Skeletal Muscle Microcirculation

Agoudemos, Melissa M.; Greene, Andrew S.

doi:10.1080/10739680500301664

Cited by 28 publications

(12 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Many tissues produce Ang-II but there are no skin data. However, data from skeletal muscle microvessels suggest local concentrations on the order of 100 pmoles/liter 45. This was similar to our lowest dose of angiotensin-II administered during prior dose-response measurements but was far less than exogenous administered angiotensin-II in current experiments.…”

Section: Discussionsupporting

confidence: 84%

Defects in Cutaneous Angiotensin-Converting Enzyme 2 and Angiotensin-(1-7) Production in Postural Tachycardia Syndrome

et al. 2009

View full text Add to dashboard Cite

Abstract-Postural tachycardia syndrome (POTS) is associated with increased plasma angiotensin II (Ang II). Ang II administered in the presence of NO synthase inhibition with nitro-L-arginine (NLA) and Ang II type 1 receptor blockade with losartan produces vasodilation during local heating in controls. We tested whether this angiotensin-mediated vasodilation occurs in POTS and whether it is related to angiotensin-converting enzyme 2 (ACE2) and Ang-(1-7). We used local cutaneous heating to 42°C and laser Doppler Flowmetry to assess NO-dependent conductance at 4 calf sites in 12 low-flow POTS and in 12 control subjects 17.6 to 25.5 years of age. We perfused Ringer's solution through intradermal microdialysis catheters and performed local heating. We perfused one catheter with NLA (10 mmol/L)ϩlo-sartan (2 g/L) and repeated heating, and NLAϩlosartanϩAng II (10 mol/L), repeating heating a third time. A second catheter received NLAϩlosartanϩAng II, heated, perfused NLAϩlosartanϩAng IIϩDX600 (1 mmol/L; a selective ACE2 inhibitor), and reheated. A third catheter received NLAϩlosartanϩAng II, heated, perfused NLAϩlosartanϩAng IIϩAng-(1-7) (100 mol/L), and reheated. The fourth catheter received Ang-(1-7) then reheated a second time only. Angiotensin-mediated vasodilation was present in control but not POTS. Ang-mediated dilation was eliminated by DX600, indicating an ACE2-related effect. Ang-mediated vasodilation was restored in POTS by Ang-(1-7). When administered alone during locally mediated heating, Ang-(1-7) improved the NO-dependent local heating response.

show abstract

Section: Discussionsupporting

confidence: 84%

Defects in Cutaneous Angiotensin-Converting Enzyme 2 and Angiotensin-(1-7) Production in Postural Tachycardia Syndrome

et al. 2009

View full text Add to dashboard Cite

show abstract

“…Skeletal muscle is reported to produce components of the renin-angiotensin system, which can lead to the local production of Ang II [28], [29]. Increased production of angiotensinogen has been observed in response to muscle stretch in both proliferating and differentiated C2C12 cells [28].…”

Section: Resultsmentioning

confidence: 99%

Angiotensin II Evokes Angiogenic Signals within Skeletal Muscle through Co-ordinated Effects on Skeletal Myocytes and Endothelial Cells

et al. 2014

View full text Add to dashboard Cite

Skeletal muscle overload induces the expression of angiogenic factors such as vascular endothelial growth factor (VEGF) and matrix metalloproteinase (MMP)-2, leading to new capillary growth. We found that the overload-induced increase in angiogenesis, as well as increases in VEGF, MMP-2 and MT1-MMP transcripts were abrogated in muscle VEGF KO mice, highlighting the critical role of myocyte-derived VEGF in controlling this process. The upstream mediators that contribute to overload-induced expression of VEGF have yet to be ascertained. We found that muscle overload increased angiotensinogen expression, a precursor of angiotensin (Ang) II, and that Ang II signaling played an important role in basal VEGF production in C2C12 cells. Furthermore, matrix-bound VEGF released from myoblasts induced the activation of endothelial cells, as evidenced by elevated endothelial cell phospho-p38 levels. We also found that exogenous Ang II elevates VEGF expression, as well as MMP-2 transcript levels in C2C12 myotubes. Interestingly, these responses also were observed in skeletal muscle endothelial cells in response to Ang II treatment, indicating that these cells also can respond directly to the stimulus. The involvement of Ang II in muscle overload-induced angiogenesis was assessed. We found that blockade of AT1R-dependent Ang II signaling using losartan did not attenuate capillary growth. Surprisingly, increased levels of VEGF protein were detected in overloaded muscle from losartan-treated rats. Similarly, we observed elevated VEGF production in cultured endothelial cells treated with losartan alone or in combination with Ang II. These studies conclusively establish the requirement for muscle derived VEGF in overload-induced angiogenesis and highlight a role for Ang II in basal VEGF production in skeletal muscle. However, while Ang II signaling is activated following overload and plays a role in muscle VEGF production, inhibition of this pathway is not sufficient to halt overload-induced angiogenesis, indicating that AT1-independent signals maintain VEGF production in losartan-treated muscle.

show abstract

“…Skeletal muscle ACE1 activity has been demonstrated in cell membrane fractions and cultured myoblasts (5). In addition, RAS components are present throughout the skeletal muscle microcirculation, including endothelial cells, vascular smooth muscle cells, and other vessel-associated cells (6).…”

mentioning

confidence: 99%

Characterization of angiotensin-converting enzymes 1 and 2 in the soleus and plantaris muscles of rats

Fernandes

Hashimoto

Oliveira

2010

Braz J Med Biol Res

View full text Add to dashboard Cite

Localization of the Renin–Angiotensin System Components to the Skeletal Muscle Microcirculation

Abstract: The current study demonstrates that within the skeletal muscle microvessels, the components and products necessary for a local renin-angiotensin system are present, but does not rule out the possibility of interaction between circulating and tissue renin-angiotensin systems.

Cited by 28 publications

References 36 publications

Defects in Cutaneous Angiotensin-Converting Enzyme 2 and Angiotensin-(1-7) Production in Postural Tachycardia Syndrome

Defects in Cutaneous Angiotensin-Converting Enzyme 2 and Angiotensin-(1-7) Production in Postural Tachycardia Syndrome

Angiotensin II Evokes Angiogenic Signals within Skeletal Muscle through Co-ordinated Effects on Skeletal Myocytes and Endothelial Cells

Characterization of angiotensin-converting enzymes 1 and 2 in the soleus and plantaris muscles of rats

Contact Info

Product

Resources

About