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BLOOD PRESSURE REGULATION BY VASCULAR TRP CHANNELS

BLOOD PRESSURE REGULATION BY VASCULAR TRP CHANNELS

Jonathan H. JAGGAR

(Tennessee, USA)

BLOOD PRESSURE REGULATION BY VASCULAR TRP CHANNELS

05:30 PM 20 April / Nisan 2018

Abstract

Systemic blood pressure is determined in part by arterial smooth muscle cells (myocytes) that alter resistance vessel tone. In vivo mechanisms that regulate myocyte contractility to control physiological blood pressure and become pathological during hypertension are poorly understood. Several Transient Receptor Potential (TRP) channels are expressed in arterial myocytes, but it is unclear if these proteins control physiological blood pressure and can be targeted to alleviate hypertension. We generated the first inducible, smooth muscle-specific knockout for a TRP channel, namely for PKD2 (also termed TRPP1, PKD2sm-/-), to investigate blood pressure regulation by this protein. Data indicate that myocyte PKD2 channel knockout dilates resistance-size systemic arteries and reduces blood pressure. We show that heterogeneous stimuli activate PKD2 channels in arteries of different organs. Regardless of the stimulus or arterial bed, PKD2 current activation in myocytes leads to vasoconstriction. Our data illustrate that hypertension is associated with an increase in the abundance of plasma membrane PKD2 channels in systemic artery myocytes. Inducible, myocyte-specific PKD2 channel knockout causes vasodilation, lowers systemic blood pressure and prevents arterial remodeling during hypertension. Furthermore, I will discuss our evidence that intravascular pressure stimulates post-translational modification of PKD2 channels in myocytes to control arterial contractility. In summary, we show that PKD2 channels are activated by distinct vasoconstrictor stimuli in arterial myocytes of different tissues, control physiological systemic blood pressure, are upregulated during hypertension and knockout reduces high blood pressure. Arterial myocyte PKD2 channels could be targeted to control blood pressure and alleviate cardiovascular diseases.