PERSPECTIVE PHYSIOLOGY
Scaffolding Builds to Reduce Blood Pressure Pooneh Bagher and Christopher J. Garland*
The luminal surface of blood vessels is lined with endothelial cells (ECs) in contact and oriented with the flow of blood. This thin monolayer of cells has a fundamental role in controlling the pressure and flow of blood, principally by providing a vasodilator drive that is disrupted in disease states such as hypertension. Minute “resistance” arteries and arterioles are central players in blood pressure regulation, and their vasodilation largely reflects endothelium-dependent hyperpolarization (EDH)—which closes voltage-dependent Ca2+ channels in the adjacent vascular smooth muscle cells (VSMCs)— rather than the release of nitric oxide. The ECs of these resistance vessels extend membrane projections called myoendothelial projections (MEPs) through perforations in the internal elastic lamina (IEL) that separates the ECs from the encircling VSMCs, allowing the ECs and VSMCs to connect through heterocellular myoendothelial gap junctions. This structural relationship enables MEPs to operate as both the source and conduit of hyperpolarization (1). EDH spreads by way of gap junctions and by K+ efflux, which initiates VSMC hyperpolarization through inwardly rectifying KIR channels and the Na+/ K+–adenosine triphosphatase (ATPase) (Fig. 1) (1). Sonkusare et al. extend evidence that EC MEPs are a central vascular signaling microdomain that underpins the precise and rapid physiological control of resistance artery diameter (2). Department of Pharmacology, University of Oxford, Oxford OX1 3QT, UK *Corresponding author. E-mail: christopher. [email protected]
In 2012, Sonkusare et al. discovered and characterized spontaneous elementary Ca2+ influx events through single transient receptor potential vanilloid 4 (TRPV4) channels in mouse mesenteric artery ECs (3). The term “TRPV4 sparklet” was coined by analogy with Ca2+ sparklets in the heart caused by influx of extracellular Ca2+ through individual voltage-dependent Ca2+ channels (4). TRPV4 sparklets were distinct from EC Ca2+ pulsars, another elementary Ca2+ signaling event defined by Nelson and colleagues. Pulsars are spontaneous spikes (
Scaffolding Builds to Reduce Blood Pressure Pooneh Bagher and Christopher J. Garland*
The luminal surface of blood vessels is lined with endothelial cells (ECs) in contact and oriented with the flow of blood. This thin monolayer of cells has a fundamental role in controlling the pressure and flow of blood, principally by providing a vasodilator drive that is disrupted in disease states such as hypertension. Minute “resistance” arteries and arterioles are central players in blood pressure regulation, and their vasodilation largely reflects endothelium-dependent hyperpolarization (EDH)—which closes voltage-dependent Ca2+ channels in the adjacent vascular smooth muscle cells (VSMCs)— rather than the release of nitric oxide. The ECs of these resistance vessels extend membrane projections called myoendothelial projections (MEPs) through perforations in the internal elastic lamina (IEL) that separates the ECs from the encircling VSMCs, allowing the ECs and VSMCs to connect through heterocellular myoendothelial gap junctions. This structural relationship enables MEPs to operate as both the source and conduit of hyperpolarization (1). EDH spreads by way of gap junctions and by K+ efflux, which initiates VSMC hyperpolarization through inwardly rectifying KIR channels and the Na+/ K+–adenosine triphosphatase (ATPase) (Fig. 1) (1). Sonkusare et al. extend evidence that EC MEPs are a central vascular signaling microdomain that underpins the precise and rapid physiological control of resistance artery diameter (2). Department of Pharmacology, University of Oxford, Oxford OX1 3QT, UK *Corresponding author. E-mail: christopher. [email protected]
In 2012, Sonkusare et al. discovered and characterized spontaneous elementary Ca2+ influx events through single transient receptor potential vanilloid 4 (TRPV4) channels in mouse mesenteric artery ECs (3). The term “TRPV4 sparklet” was coined by analogy with Ca2+ sparklets in the heart caused by influx of extracellular Ca2+ through individual voltage-dependent Ca2+ channels (4). TRPV4 sparklets were distinct from EC Ca2+ pulsars, another elementary Ca2+ signaling event defined by Nelson and colleagues. Pulsars are spontaneous spikes (
