scholarly journals Arterial smooth muscle cell PKD2 (TRPP1) channels control systemic blood pressure

2018 ◽  
Author(s):  
Simon Bulley ◽  
Carlos Fernandez-Pena ◽  
Raquibul Hasan ◽  
M. Dennis Leo ◽  
Padmapriya Muralidharan ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Smooth Muscle ◽  
Smooth Muscle Cell ◽  
Muscle Cell ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Systemic Blood Pressure ◽  
Systemic Blood ◽  
Arterial Smooth Muscle

AbstractSystemic blood pressure is determined, in part, by arterial smooth muscle cells (myocytes). Several Transient Receptor Potential (TRP) channels are proposed to be expressed in arterial myocytes, but it is unclear if these proteins control physiological blood pressure and contribute to hypertension in vivo. We generated the first inducible, smooth muscle-specific knockout for a TRP channel, namely for PKD2 (TRPP1), to investigate arterial myocyte and blood pressure regulation by this protein. Using this model, we show that intravascular pressure and α1-receptors activate PKD2 channels in arterial myocytes of different systemic organs. PKD2 channel activation in arterial myocytes leads to an inward Na+ current, membrane depolarization and vasoconstriction. Inducible, smooth muscle cell-specific PKD2 knockout lowers both physiological blood pressure and hypertension and prevents pathological arterial remodeling during hypertension. In summary, we show for the first time that arterial myocyte PKD2 channels control systemic blood pressure and targeting reduces high blood pressure.

scholarly journals Arterial smooth muscle cell PKD2 (TRPP1) channels regulate systemic blood pressure

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Simon Bulley ◽  
Carlos Fernández-Peña ◽  
Raquibul Hasan ◽  
M Dennis Leo ◽  
Padmapriya Muralidharan ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Smooth Muscle ◽  
Smooth Muscle Cell ◽  
Muscle Cell ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Systemic Blood Pressure ◽  
Trp Channel ◽  
Systemic Blood ◽  
Arterial Smooth Muscle

Systemic blood pressure is determined, in part, by arterial smooth muscle cells (myocytes). Several Transient Receptor Potential (TRP) channels are proposed to be expressed in arterial myocytes, but it is unclear if these proteins control physiological blood pressure and contribute to hypertension in vivo. We generated the first inducible, smooth muscle-specific knockout mice for a TRP channel, namely for PKD2 (TRPP1), to investigate arterial myocyte and blood pressure regulation by this protein. Using this model, we show that intravascular pressure and α1-adrenoceptors activate PKD2 channels in arterial myocytes of different systemic organs. PKD2 channel activation in arterial myocytes leads to an inward Na+ current, membrane depolarization and vasoconstriction. Inducible, smooth muscle cell-specific PKD2 knockout lowers both physiological blood pressure and hypertension and prevents pathological arterial remodeling during hypertension. Thus, arterial myocyte PKD2 controls systemic blood pressure and targeting this TRP channel reduces high blood pressure.

scholarly journals Author response: Arterial smooth muscle cell PKD2 (TRPP1) channels regulate systemic blood pressure

2018 ◽  
Author(s):  
Simon Bulley ◽  
Carlos Fernández-Peña ◽  
Raquibul Hasan ◽  
M Dennis Leo ◽  
Padmapriya Muralidharan ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Smooth Muscle ◽  
Smooth Muscle Cell ◽  
Muscle Cell ◽  
Systemic Blood Pressure ◽  
Author Response ◽  
Arterial Smooth Muscle Cell ◽  
Systemic Blood ◽  
Arterial Smooth Muscle

scholarly journals Arterial smooth muscle cell PKD2 (TRPP1) channels control systemic blood pressure

2018 ◽  
Vol 32 (S1) ◽  
Author(s):  
Carlos Fernandez‐Pena ◽  
Simon Bulley ◽  
Raquibul Hasan ◽  
M. Dennis Leo ◽  
Padmapriya Muralidharan ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Smooth Muscle ◽  
Smooth Muscle Cell ◽  
Muscle Cell ◽  
Systemic Blood Pressure ◽  
Arterial Smooth Muscle Cell ◽  
Systemic Blood ◽  
Arterial Smooth Muscle

scholarly journals Author response: Arterial smooth muscle cell PKD2 (TRPP1) channels regulate systemic blood pressure

2018 ◽  
Author(s):  
Simon Bulley ◽  
Carlos Fernández-Peña ◽  
Raquibul Hasan ◽  
M Dennis Leo ◽  
Padmapriya Muralidharan ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Smooth Muscle ◽  
Smooth Muscle Cell ◽  
Muscle Cell ◽  
Systemic Blood Pressure ◽  
Author Response ◽  
Arterial Smooth Muscle Cell ◽  
Systemic Blood ◽  
Arterial Smooth Muscle

scholarly journals Correction: Arterial smooth muscle cell PKD2 (TRPP1) channels regulate systemic blood pressure

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Simon Bulley ◽  
Carlos Fernández-Peña ◽  
Raquibul Hasan ◽  
M Dennis Leo ◽  
Padmapriya Muralidharan ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Smooth Muscle ◽  
Smooth Muscle Cell ◽  
Muscle Cell ◽  
Systemic Blood Pressure ◽  
Arterial Smooth Muscle Cell ◽  
Systemic Blood ◽  
Arterial Smooth Muscle

Heparinase III limits rat arterial smooth muscle cell proliferation in vitro and in vivo

1998 ◽  
Vol 351 (1) ◽  
pp. 79-83 ◽  
Author(s):  
Paul J Silver ◽  
Jean-Pierre Moreau ◽  
Elizabeth Denholm ◽  
YongQing Lin ◽  
Linh Nguyen ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Smooth Muscle ◽  
Smooth Muscle Cell ◽  
Muscle Cell ◽  
Smooth Muscle Cell Proliferation ◽  
Arterial Smooth Muscle Cell ◽  
Arterial Smooth Muscle ◽  
Proliferation In Vitro

scholarly journals TRPV1 expressed throughout the arterial circulation enables inflammatory vasoconstriction

2020 ◽  
Author(s):  
Thieu X. Phan ◽  
Hoai T. Ton ◽  
Hajnalka Gulyás ◽  
Róbert Pórszász ◽  
Attila Tóth ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Skeletal Muscle ◽  
Smooth Muscle ◽  
Ex Vivo ◽  
Systemic Blood Pressure ◽  
Sensory Nerves ◽  
Systemic Blood ◽  
Signaling Mechanism ◽  
Arterial Circulation

AbstractThe capsaicin receptor, TRPV1, is a key ion channel involved in inflammatory pain signaling. Although mainly studied in sensory nerves, there are reports of TRPV1 expression in isolated segments of the vasculature, but whether the channel localizes to vascular endothelium or smooth muscle is controversial and the distribution and functional roles of TRPV1 in arteries remain unknown. We mapped functional TRPV1 expression throughout the mouse arterial circulation. Analysis of reporter mouse lines TRPV1PLAP-nlacZ and TRPV1-Cre:tdTomato combined with Ca2+ imaging revealed specific localization of TRPV1 to smooth muscle of terminal arterioles in the heart, fat and skeletal muscle. Capsaicin evoked inward currents and raised intracellular Ca2+ levels in arterial smooth muscle cells, constricted arterioles ex vivo and in vivo and increased systemic blood pressure in mice and rats. Further, capsaicin markedly and dose-dependently reduced coronary flow. Pharmacologic and/or genetic disruption of TRPV1 abolished all these effects of capsaicin as well as vasoconstriction triggered by lysophosphatidic acid, a bioactive lipid generated by platelets and atherogenic plaques. Notably, ablation of sensory nerves did not affect the responses to capsaicin revealing a vascular smooth muscle-restricted signaling mechanism. Moreover, unlike in sensory nerves, TRPV1 function in arteries was resistant to activity-induced desensitization. Thus, TRPV1 activation in vascular myocytes of resistance arterioles enables a persistent depolarizing current, leading to constriction of coronary, skeletal muscle, and adipose arterioles and a sustained increase in systemic blood pressure.

scholarly journals Doxorubicin Impairs Smooth Muscle Cell Contraction: Novel Insights in Vascular Toxicity

2021 ◽  
Vol 22 (23) ◽  
pp. 12812
Author(s):  
Matthias Bosman ◽  
Dustin N. Krüger ◽  
Kasper Favere ◽  
Callan D. Wesley ◽  
Cédric H. G. Neutel ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Arterial Stiffness ◽  
Smooth Muscle Cell ◽  
Muscle Cell ◽  
Vascular Reactivity ◽  
Transient Receptor Potential ◽  
Ex Vivo ◽  
Receptor Potential ◽  
Transient Receptor Potential Channels

Clinical and animal studies have demonstrated that chemotherapeutic doxorubicin (DOX) increases arterial stiffness, a predictor of cardiovascular risk. Despite consensus about DOX-impaired endothelium-dependent vasodilation as a contributing mechanism, some studies have reported conflicting results on vascular smooth muscle cell (VSMC) function after DOX treatment. The present study aimed to investigate the effects of DOX on VSMC function. To this end, mice received a single injection of 4 mg DOX/kg, or mouse aortic segments were treated ex vivo with 1 μM DOX, followed by vascular reactivity evaluation 16 h later. Phenylephrine (PE)-induced VSMC contraction was decreased after DOX treatment. DOX did not affect the transient PE contraction dependent on Ca2+ release from the sarcoplasmic reticulum (0 mM Ca2+), but it reduced the subsequent tonic phase characterised by Ca2+ influx. These findings were supported by similar angiotensin II and attenuated endothelin-1 contractions. The involvement of voltage-gated Ca2+ channels in DOX-decreased contraction was excluded by using levcromakalim and diltiazem in PE-induced contraction and corroborated by similar K+ and serotonin contractions. Despite the evaluation of multiple blockers of transient receptor potential channels, the exact mechanism for DOX-decreased VSMC contraction remains elusive. Surprisingly, DOX reduced ex vivo but not in vivo arterial stiffness, highlighting the importance of appropriate timing for evaluating arterial stiffness in DOX-treated patients.

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