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This MiniReview is focused on the nature of intercellular signalling along the endothelium that helps to co-ordinate blood flow control in vascular resistance networks. Vasodilation initiated by contracting skeletal muscle ascends from arterioles within the tissue to encompass resistance arteries upstream and thereby increase blood flow during exercise. In resistance vessels, acetylcholine microiontophoresis or intracellular current injection initiates hyperpolarization that conducts through gap junction channels (GJCs) along the vessel wall resulting in conducted vasodilation (CVD). Both ascending vasodilation and CVD are eliminated with endothelial cell (EC) disruption, pointing to common signalling events and mutual dependence upon EC integrity. As demonstrated by electrical coupling and dye transfer during intracellular recording, their longitudinal orientation and robust expression of GJCs enable ECs to play a predominant role in CVD. Once conduction is initiated, a major interest centres on whether CVD is purely passive or involves additional 'active' signalling events. Here, we discuss components for Ca2+ and electrical signalling with an emphasis on intercellular coupling through endothelial GJCs. We stress the importance of understanding relationships between intracellular Ca2+ dynamics, EC hyperpolarization and CVD while integrating findings from isolated ECs into more complex interactions in vivo. Whereas endothelial dysfunction accompanies cardiovascular disease and the components of intra- and inter-cellular signalling are increasingly well defined, little is known of how Ca2+ signalling and electrical conduction along microvascular endothelium are altered in diseased states. Thus, greater insight into how these relationships are governed and interact is a key goal for continued research efforts. [ABSTRACT FROM AUTHOR]

Regular physical activity (endurance training, ET) has a strong positive link with cardiovascular health. The aim of this review is to draw together the current knowledge on gene expression in different cell types comprising the vessels of the circulatory system, with special emphasis on the endothelium, and how these gene products interact to influence vascular health. The effect beneficial effects of ET on the endothelium are believed to result from increased vascular shear stress during ET bouts. A number of mechanosensory mechanisms have been elucidated that may contribute to the effects of ET on vascular function, but there are questions regarding interactions among molecular pathways. For instance, increases in flow brought on by ET can reduce circulating levels of viscosity and haemostatic and inflammatory variables that may interact with increased shear stress, releasing vasoactive substances such as nitric oxide and prostacyclin, decreasing permeability to plasma lipoproteins as well as the adhesion of leucocytes. At this time the optimal rate-of-flow and rate-of-change in flow for determining whether anti-atherogenic or pro-atherogenic processes proceed remain unknown. In addition, the impact of haemodynamic variables differs with vessel size and tissue type in which arteries are located. While the hurdles to understanding the mechanism responsible for ET-induced alterations in vascular cell gene expression are significant, they in no way undermine the established benefits of regular physical activity to the cardiovascular system and to general overall health. This review summarizes current understanding of control of vascular cell gene expression by exercise and how these processes lead to improved cardiovascular health. [ABSTRACT FROM AUTHOR]

To meet the metabolic demands of skeletal muscle, the vasculature supplying these vascular beds has to be connected to respond in a coordinated uniform manner, thus providing the necessary oxygen and nutrients during increased activity. The skeletal muscle microcirculation is the major resistance network controlling vascular blood supply and it is the integrity of the endothelium lining the blood vessels that is paramount in facilitating this action. Aging is a major risk factor for cardiovascular disease and is associated with significant increases in inflammatory agents that negatively impact the vasculature. Several inflammatory agents such as cytokines (tumor necrosis factor-a), advanced glycation products (AGEs), and matrix metalloproteinases (MMPs) along with storage cells for inflammatory mediators (mast cells) are associated with a chronic “low-grade inflammation” state that has been observed over the course of the aging process. Current research suggests that these age-related increases in inflammatory agents can disrupt the microvascular endothelium and thus impair blood flow. This impairment could exacerbate the common age-related disease states such as hypertension, diabetes, congestive heart failure, and sarcopenia, leading to increased mortality and morbidity. [ABSTRACT FROM AUTHOR]

Control of blood flow to skeletal muscle depends on the vasomotor tone present in the resistance vasculature. Although muscle blood flow has been shown to decline with advancing age, our knowledge of how alterations of reactivity of the resistance vasculature contribute to reduced delivery or altered distribution of blood in the aged is limited. Recent work has demonstrated that age alters the reactivity of resistance arteries and arterioles from skeletal muscle, and that impairment of both vasodilator and vasoconstrictor responses occurs with advancing age. The alterations in cellular mechanisms that contribute to age-related impairment of vasoreactive responses encompass both the vascular endothelium and smooth muscle, and differ in muscles of varying function and fiber type. Current research suggests that some degree of age-induced endothelial dysfunction occurs in resistance arteries and arterioles from most skeletal muscle; however, the severity of endothelial impairment appears greater in resistance arteries and arterioles from highly oxidative locomotory muscles. Age-related impairment of vasoconstrictor responses to metabolites and endogenous constrictor agents has also been documented. These age-related reductions in vasoreactivity that occur in the skeletal muscle resistance vasculature may contribute to inadequate delivery or distribution of blood flow during exercise and ultimately be a factor in loss of exercise capacity that occurs with advancing age. [ABSTRACT FROM AUTHOR]

SUMMARY 1. The aim of the present study was to investigate the effects of α -adrenoceptor blockade (phentolamine), β -adrenoceptor blockade (propranolol), neuropeptide Y1 receptor blockade and neurogenic blockade (brachial plexus) on endothelium-dependent vasodilation (EDV) in the human forearm. 2. Forty-four young healthy volunteers underwent forearm blood flow (FBF) measurements, using venous occlusion plethysmography, during local intra-arterial infusions of methacholine (MCh; inducing EDV) and sodium nitroprusside (SNP; inducing endothelium-independent vasodilation (EIDV)). These measurements were undertaken at baseline and were repeated with either concomitant local intra-arterial infusion of phentolamine (n = 8), propranolol (n = 7) or saline (n = 6) in the forearm, neuropeptide Y1 receptor blockade (n = 12) given i.v. or during axillary plexus blockade (n = 11). 3. Both α -adrenoceptor blockade and neurogenic blockade induced an upward shift in the dose–response curve for both EDV and EIDV. β -Adrenoceptor blockade did not change resting FBF or EIDV, but induced a significant decrease in EDV (P = 0.015). Neuropeptide Y1 receptor blocker induced no significant changes in resting FBF, EDV and EIDV and neither did saline. No changes in blood pressure or heart rate were induced by any of the blockades. 4. Whereas β -adrenoceptor blockade impaired EDV, α -adrenoceptor blockade and neurogenic blockade caused a general vasodilation that was not endothelium dependent. Neuropeptide Y does not seem to influence blood flow in the resting forearm. [ABSTRACT FROM AUTHOR]

The present study, involving 56 healthy subjects from a health screening, was undertaken to address some methodological questions regarding the measurement of endothelial function using local intra-arterial infusions of metacholine (2 and 5 μg min-1) to evaluate endothelium-dependent vasodilatation, and sodium nitroprusside (SNP, 5 and 10 μg min-1) to evaluate endothelium-independent vasodilatation. Forearm blood flow (FBF) was measured by venous occlusion plethysmography. The ratio of FBF during the highest dose of metacholine to FBF during the highest dose of SNP was used as an index of endothelial function. In 10 young volunteers the procedure was repeated after 2 h and again after 3 weeks in order to study short-term and long-term reproducibility of the method. Neither the vasodilatatory response to metacholine (r = 0·006) nor that to SNP (r = 0·08) was related to resting FBF. Neither the circumference nor the length of the arm was related to endothelial function (r = 0·01-0·11), as evaluated by the FBF on metacholine to nitroprusside ratio (mean 1·3 ± 0·3 SD). The use of a wrist cuff to exclude hand circulation, or not, did not influence the evaluation of endothelial function significantly. Maximal FBF after 3 min of arterial occlusion of the forearm was significantly related to blood flow during both metacholine (r = 0·53, P < 0·01) and nitroprusside infusion (r = 0·36, P < 0·05), but not to the FBF on metacholine to nitroprusside ratio (r = 0·01). The short-term and long-term reproducibility of FBF during vasodilatation with metacholine and SNP was good (r = 0·89-0·97, P < 0·001), while the individual measurements for resting FBF were less reproducible when repeated after 3 weeks... [ABSTRACT FROM AUTHOR]

Please cite this paper as: Welsh DG, Taylor MS. Cell-cell communication in the resistance vasculature: the past, present, and future. Microcirculation 19: 377-378, 2012. Abstract Cell-cell communication among neighboring vascular cells plays an important role in blood flow control. In this overview, we highlight a series of expert opinion articles focused on key issues related to the foundational nature and functional importance of electrical and second messenger communication. These manuscripts are written in an opinionated manner to provoke thought and to illuminate new emerging areas of investigation. [ABSTRACT FROM AUTHOR]

ATP-dependent chromatin-remodeling complexes such as the mammalian SWI/SNF-related complexes BAF and PBAF can alter the conformation or position of nucleosomes, thereby affecting the ability of large nuclear factors to access gene promoters. It is becoming increasingly clear that complexes such as these are necessary to achieve proper temporal and spatial patterns of gene expression in the developing embryo. BAF and PBAF complexes contain one of two ATPase subunits: BRM or BRG1. In order to assess the role of BAF/PBAF complexes in vascular development, we have generated mice lacking both Brm and Brg1 in their endothelium. Our data indicate that embryos lacking endothelial Brg1 are identical to embryos lacking both endothelial Brg1 and Brm, thereby revealing the importance of Brg1 over Brm in developing endothelium. Furthermore, embryos lacking endothelial Brg1 die at midgestation with normal embryonic vasculature but defectively remodeled yolk sac vasculature. We hypothesize that this phenotype results from a compromised arterial supply of blood flow to the mutant yolk sacs. Importantly, our results help elucidate the contribution of epigenetic regulation to the process of vascular development. Ongoing efforts include identification of target genes that require BAF/PBAF-mediated modification for activation or repression during vascular development. [ABSTRACT FROM AUTHOR]