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Steven S Segal

Publications and source records attributed to Steven S Segal.

At least 19 recordsLinked to original sources

Guidelines for evaluating endothelial function in vascular tissue.

The endothelium plays a central role in maintaining vascular homeostasis by orchestrating vascular tone, inflammation, healing, permeability, and thrombosis. Assessing endothelial function in vascular tissue is essential for understanding the cellular and molecular mechanisms underlying cardiovascular physiology and pathology. Traditional approaches, such as wire and pressure myography, have been instrumental in defining endothelium-dependent responses and identifying key pharmacological targets. However, the complexity and heterogeneity of endothelial cells across vascular beds and their dynamic phenotypic changes in health and disease necessitate the incorporation of new investigative strategies. Emerging methodologies, including bulk and single-cell transcriptomics, proteomics, and advanced imaging, now provide unprecedented insights into endothelial cell diversity and function. A team of leading experts in the field, who collectively reached a consensus on the most widely used techniques to evaluate endothelial function, developed these guidelines. The document establishes best practices for assessing endothelial function, from endothelial cell cultures to isolated vascular tissues, integrating conventional functional assays with modern molecular approaches. By fostering methodological consistency and embracing innovation, our goal is to enhance rigor, reproducibility, understanding, and discovery in endothelial biology.

Humans↗

Electromechanical and pharmacomechanical signalling pathways for conducted vasodilatation along endothelium of hamster feed arteries.

Conducted vasodilatation (CVD) reflects the initiation and rapid (>mm s(-1)) spread of hyperpolarization along the endothelium and into smooth muscle. The ion channels that initiate CVD remain unclear as do signalling pathways that may complement electromechanical relaxation. Using isolated pressurized (75 mmHg; 37 degrees C) feed arteries (n=63; diameter: rest: 53 +/- 2 microm, maximal: 98 +/- 2 microm) from hamster retractor skeletal muscle, we investigated the contribution of calcium-activated potassium channels (KCa) and endothelium-derived autacoids to CVD. Local delivery (1 microm micropipette tip; 500-2000 ms pulse) of acetylcholine (ACh) at the downstream end initiated a local increase in endothelial cell [Ca2+]i (Fura-PE3; Deltaratio 340/380 nm = 0.215 +/- 0.032) that preceded CVD along the entire vessel. During local perifusion with KCa antagonists, iberiotoxin (5 microm) had no effect, but charybdotoxin (CTX, 5 microm) + apamin (APA, 10 microm) abolished CVD reversibly. Remarkably, this local inhibition of KCa unmasked a 'slow-conducted vasodilatation' (SCVD) that spread >1200 microm at approximately 21 microm s(-1) (n=27). Recorded 500 microm upstream from the ACh stimulus, a rise in endothelial cell [Ca2+]i (Deltaratio 340/380 nm) = 0.146 +/- 0.017; P<0.05) preceded SCVD (Deltadiameter = 14 +/- 3 microm) by approximately 10 s. Before KCa inhibition, antagonism of nitric oxide synthase (Nomega-nitro-L-arginine, 250 microm; l-NNA) and cyclooxygenase (indomethacin, 5 microm; INDO) had no effect on the amplitude of CVD yet response duration decreased by one-third (P<0.05). During local CTX + APA perifusion, L-NNA + INDO abolished SCVD while conducted [Ca2+]i responses remained intact. Thus, ACh triggers electromechanical relaxation of smooth muscle cells along the vessel initiated by local KCa, and the ensuing 'wave' of Ca2+ along the endothelium releases autacoids to promote pharmacomechanical relaxation.

Acetylcholine↗

Propagation of calcium waves along endothelium of hamster feed arteries.

An increase in tissue blood flow requires relaxation of smooth muscle cells along entire branches of the resistance vasculature. Whereas the spread of hyperpolarization along the endothelium can coordinate smooth muscle cell relaxation, complementary signaling events have been implicated in the conduction of vasodilation. We tested the hypothesis that Ca(2+) waves propagate from cell to cell along the endothelium of feed arteries exhibiting spontaneous vasomotor tone. Feed arteries of the hamster retractor muscle were isolated, pressurized to 75 mmHg at 37 degrees C, and developed myogenic tone spontaneously. Smooth muscle cells and endothelial cells were loaded with the Ca(2+) indicator Fluo-4. An acetylcholine stimulus was delivered locally using microiontophoresis (1-microm pipette tip, 1 microA, 1 s), and Ca(2+) signaling within and along respective cell layers was determined using laser-scanning confocal microscopy. Acetylcholine triggered an increase in intracellular Ca(2+) concentration ([Ca(2+)](i)) of endothelial cells at the site of stimulation that preceded two distinct events: 1) a rapid synchronous decrease in smooth muscle [Ca(2+)](i) along the entire vessel and 2) an ensuing Ca(2+) wave that propagated bidirectionally along the endothelium at approximately 111 microm/s for distances exceeding 1 mm. Maximal dilation of vessels with either nifedipine (1 microM) or sodium nitroprusside (SNP, 100 microM) reduced the distance that Ca(2+) waves traveled to approximately 300 microm (P < 0.05). Thus Ca(2+) waves propagate along the endothelium of resistance vessels with vasomotor tone, and this signaling pathway is compromised during maximal dilation with nifedipine or SNP.

Animals↗

A macroporous hydrogel for the coculture of neural progenitor and endothelial cells to form functional vascular networks in vivo.

A microvascular network is critical for the survival and function of most tissues. We have investigated the potential of neural progenitor cells to augment the formation and stabilization of microvascular networks in a previously uncharacterized three-dimensional macroporous hydrogel and the ability of this engineered system to develop a functional microcirculation in vivo. The hydrogel is synthesized by cross-linking polyethylene glycol with polylysine around a salt-leached polylactic-co-glycolic acid scaffold that is degraded in a sodium hydroxide solution. An open macroporous network is formed that supports the efficient formation of tubular structures by brain endothelial cells. After subcutaneous implantation of hydrogel cocultures in mice, blood flow in new microvessels was apparent at 2 weeks with perfused networks established on the surface of implants at 6 weeks. Compared to endothelial cells cultured alone, cocultures of endothelial cells and neural progenitor cells had a significantly greater density of tubular structures positive for platelet endothelial cell adhesion molecule-1 at the 6-week time point. In implant cross sections, the presence of red blood cells in vessel lumens confirmed a functional microcirculation. These findings indicate that neural progenitor cells promote the formation of endothelial cell tubes in coculture and the development of a functional microcirculation in vivo. We demonstrate a previously undescribed strategy for creating stable microvascular networks to support engineered tissues of desired parenchymal cell origin.

Animals↗

Arteriolar smooth muscle Ca2+ dynamics during blood flow control in hamster cheek pouch.

Intracellular calcium concentration ([Ca2+]i) governs the contractile status of arteriolar smooth muscle cells (SMC). Although studied in vitro, little is known of SMC [Ca2+]i dynamics during the local control of blood flow. We tested the hypothesis that the rise and fall of SMC [Ca2+]i underlies arteriolar constriction and dilation in vivo. Aparenchymal segments of second-order arterioles (diameter 35 +/- 2 microm) were prepared in the superfused cheek pouch of anesthetized hamsters (n = 18) and perifused with the ratiometric dye fura PE-3 (AM) to load SMC (1 microM, 20 min). Resting SMC [Ca2+]i was 406 +/- 37 nM. Elevating superfusate O2 from 0 to 21% produced constriction (11 +/- 2 microm) that was unaffected by dye loading; [Ca2+]i increased by 108 +/- 53 nM (n = 6, P < 0.05). Cycling of [Ca2+]i during vasomotion (amplitude, 150 +/- 53 nM; n = 4) preceded corresponding diameter changes (7 +/- 1 microm) by approximately 2 s. Microiontophoresis (1 microm pipette tip; 1 microA, 1 s) of phenylephrine (PE) transiently increased [Ca2+]i by 479 +/- 64 nM (n = 8, P < 0.05) with constriction (26 +/- 3 microm). Flushing blood from the lumen with saline increased fluorescence at 510 nm by approximately 45% during excitation at both 340 and 380 nm with no difference in resting [Ca2+]i, diameter or respective responses to PE (n = 7). Acetylcholine microiontophoresis (1 microA, 1 s) transiently reduced resting SMC [Ca2+]i by 131 +/- 21 nM (n = 6, P < 0.05) with vasodilation (17 +/- 1 microm). Superfusion of sodium nitroprusside (10 microM) transiently reduced SMC [Ca2+]i by 124 +/- 18 nM (n = 6, P < 0.05), whereas dilation (23 +/- 5 microm) was sustained. Resolution of arteriolar SMC [Ca2+]i in vivo discriminates key signaling events that govern the local control of tissue blood flow.

Animals↗

Innate control of adaptive immunity via remodeling of lymph node feed arteriole.

The adaptive immune system relies on rare cognate lymphocytes to detect pathogen-derived antigens. Naïve lymphocytes recirculate through secondary lymphoid organs in search of cognate antigen. Here, we show that the naïve-lymphocyte recirculation pattern is controlled at the level of innate immune recognition, independent of antigen-specific stimulation. We demonstrate that inflammation-induced lymphocyte recruitment to the lymph node is mediated by the remodeling of the primary feed arteriole, and that its physiological role is to increase the efficiency of screening for rare antigen-specific lymphocytes. Our data reveal a mechanism of innate control of adaptive immunity: by increasing the pool of naïve lymphocytes for detection of foreign antigens via regulation of vascular input to the local lymph node.

Animals↗

Rapid dilation of arterioles with single contraction of hamster skeletal muscle.

Skeletal muscle blood flow increases rapidly with exercise onset, but little is known of where or how the rapid onset of vasodilation (ROV) is governed within the microcirculation. In the retractor muscle of anesthetized hamsters (n = 26), we tested the following: 1) where in the resistance network ROV occurred, 2) how microvascular responses were affected by the duration of contraction, and 3) whether ROV involved muscarinic receptor activation. Single tetanic contractions were evoked using supramaximal field stimulation (100 Hz) to depolarize motor end plates. In response to a 200-ms contraction, red blood cell (rbc) velocity (V(rbc)) in feed arteries (FA; rest: 17.8 +/- 2 mm/s) increased within 1 s; a transient first peak (P1; 50 +/- 7% increase) occurred at approximately 5 s; and a second peak (P2; 50 +/- 15% increase) occurred at approximately 15-20 s. For vasodilation, P1 increased in frequency from proximal FA (2/7) and 1A arterioles (2/7) to distal 2A (4/7) and 3A (7/8) arterioles (P < 0.05). Relative to resting (and maximal, 10 microM sodium nitroprusside) diameters, P1 increased from proximal (FA, 3 +/- 2% from 57 +/- 5 microm) to distal (3A, 27 +/- 6% from 14 +/- 1 microm) vessel branches (P < 0.05). P2 was manifest in all vessels and increased relative to resting diameters from FA (11 +/- 3%) to 3A (36 +/- 6%) branches (P < 0.01). Extending a contraction from 200 to 1,000 ms (tension x time integral from 17 +/- 2 to 73 +/- 4 mN/mm2 x s) increased P1 and P2 for V(rbc) and for diameter (P < 0.05) while reducing the time of onset for P2 (P < 0.05). Superfusion with atropine (10 microM) attenuated P1 of vasodilation (200 ms contraction) from 26 +/- 8% to 6 +/- 2% (n = 7 across branches; P < 0.05) and reduced the diameter x time integral by 46 +/- 13% (P < 0.05) without changing P2. We conclude that ROV in the hamster retractor muscle is initiated in distal arterioles, increases with the duration of muscle contraction, and involves muscarinic receptor activation.

Animals↗

Defining electrical communication in skeletal muscle resistance arteries: a computational approach.

Vascular cells communicate electrically to coordinate their activity and control tissue blood flow. To foster a quantitative understanding of this fundamental process, we developed a computational model that was structured to mimic a skeletal muscle resistance artery. Each endothelial cell and smooth muscle cell in our virtual artery was treated as the electrical equivalent of a capacitor coupled in parallel with a non-linear resistor representing ionic conductance; intercellular gap junctions were represented by ohmic resistors. Simulations revealed that the vessel wall is not a syncytium in which electrical stimuli spread equally to all constitutive cells. Indeed, electrical signals spread in a differential manner among and between endothelial cells and smooth muscle cells according to the initial stimulus. The predictions of our model agree with physiological data from the feed artery of the hamster retractor muscle. Cell orientation and coupling resistance were the principal factors that enable electrical signals to spread differentially along and between the two cell types. Our computational observations also illustrated how gap junctional coupling enables the vessel wall to filter and transform transient electrical events into sustained voltage responses. Functionally, differential electrical communication would permit discrete regions of smooth muscle activity to locally regulate blood flow and the endothelium to coordinate regional changes in tissue perfusion.

Animals↗

Neurovascular alignment in adult mouse skeletal muscles.

OBJECTIVE: Muscle blood flow increases with motor unit recruitment. The physical relationships between somatic motor nerves, which control muscle fiber contraction, and arterioles, which control microvascular perfusion, are unexplored. The authors tested the hypothesis that motor axons align with arterioles in adult skeletal muscle. METHODS: Transgenic mice (C57BL/6 background, n = 5; 10 months of age) expressing yellow fluorescent protein in all motor nerves underwent vascular casting (Microfil). Excised epitrochlearis, gracilis, gluteus maximus, and spinotrapezius muscles were imaged at 380x and 760x and a computer-integrated tracing system (Neurolucida) was used to acquire 3-dimensional digital renderings of entire arteriolar and neural networks within each muscle. RESULTS: Arteriolar networks were typically approximately 3-fold longer than neural networks. Nerves coursed with arterioles until terminating at motor endplates. Across muscles, proximity analyses revealed that approximately 75% of total nerve length (9.8-48.8 mm) lay within 200 microm of the nearest arteriole (diameters of 15-60 microm). CONCLUSIONS: Somatic motor nerves and arterioles align closely within adult mammalian skeletal muscle. Understanding the signals governing neurovascular alignment may hold important clues for the advancement of tissue engineering and regeneration.

Animals↗

Sympathetic neural inhibition of conducted vasodilatation along hamster feed arteries: complementary effects of alpha1- and alpha2-adrenoreceptor activation.

Vasodilatation initiated on arterioles of skeletal muscle ascends into the proximal feed arteries through cell-to-cell conduction along the endothelium and into smooth muscle. Whereas perivascular sympathetic nerve activity (SNA) can inhibit conducted vasodilatation and restrict muscle blood flow, the signalling events mediating this interaction are poorly defined. Therefore, using isolated pressurized (75 mmHg) feed arteries (diameter (microm) at rest = 53 +/- 3; maximum = 99 +/- 2; n = 86) of the hamster retractor muscle, we tested the hypothesis that distinct yet complementary signalling pathways underlie the ability of SNA to inhibit conduction. Conducted vasodilatation was initiated using ACh microiontophoresis (1 microA; 250, 500 and 1000 ms) and SNA was initiated using local field stimulation (30-50 V; 1 ms at 2, 8 and 16 Hz). With vasodilatations of 5-20 microM, conduction increased with ACh pulse duration and was inhibited progressively as the frequency of SNA increased. During SNA, conduction was partially restored with inhibition of alpha1- (0.1 microM prazosin) or alpha2- (0.1 microM RX821002) adrenoreceptors and fully restored with both antagonists present. Activating alpha1- (50 nM phenylephrine) or alpha2- (1 microM UK 14,304) adrenoreceptors inhibited conduction partially and their simultaneous activation inhibited conduction cumulatively (P < 0.05). Elevated [K+]o (30 or 40 mM) or phorbol esters (0.5 microM) also inhibited conduction yet similar constriction with l-NNA (50 microM) or Bay K 8644 (10 nM) did not. Thus, the activation of alpha1- and alpha2-adrenoreceptors inhibits conducted vasodilatation through complementary signalling events. With robust coupling along the endothelium, our modelling predicts that the inhibition of conduction by SNA can be explained by reduced electrical coupling through myoendothelial gap junctions or greater current leak across smooth muscle cell membranes.

Adrenergic Agonists↗

Arteriolar network architecture and vasomotor function with ageing in mouse gluteus maximus muscle.

Physical diminishes with ageing, but little is known of how the microvascular supply to skeletal muscle fibres is affected. To test the hypothesis that ageing alters blood flow control, we investigated network architecture and vasomotor responses of arterioles in the gluteus maximus muscle of young (2-3 months), adult (12-14 months) and old (18-20 months) C57BL6 male mice (n = 83) (Young, Adult and Old, respectively). Microvascular casts revealed that the total number, length and surface area of arteriolar segments (diameter, 10-50 microm) were not significantly different across age-groups. However, for arterioles with diameter of 30 microm, tortuosity and branch angles increased with age (P < 0.05). In anaesthetized mice, second-order (2A) distributing arterioles had similar resting (17 +/- 1 microm) and maximal (37 +/- 1 microm) diameters and similar responsiveness to cumulative (10(-10)-10(-4) M) superfusion of acetylcholine or phenylephrine. With superfusate oxygen level raised from 0 to 21%, 2A arteriolar constriction in Young (11 +/- 1 microm) was greater (P < 0.05) than Adult and Old (5 +/- 1 microm). Observed 1 mm upstream from microiontophoresis of ACh (1 microA, 1 s), conducted vasodilatation was 10 +/- 1 microm in Young, 17 +/- 1 microm in Adult and 6 +/- 1 microm in Old (P < 0.05). With muscle contractions (2, 4 and 8 Hz; 30 s) arteriolar diameter increased similarly across age-groups (6 +/- 1, 11 +/- 1 and 18 +/- 1 microm, respectively). Muscle mass and active tension were similar across age-groups yet postcontraction vasodilatation recovered more rapidly in Old versus Adult and Young (P < 0.05). With arteriolar network architecture maintained during ageing, the impairment in conducted vasodilatation and attenuation of postcontraction vasodilatation may compromise exercise tolerance.

Acetylcholine↗

Connexin expression and conducted vasodilation along arteriolar endothelium in mouse skeletal muscle.

Functional hyperemia requires the coordination of smooth muscle cell relaxation along and between branches of the arteriolar network. Vasodilation is conducted from cell to cell along the arteriolar wall through gap junction channels composed of connexin protein subunits. Within skeletal muscle, it is unclear whether arteriolar endothelium, smooth muscle, or both cell layers provide the cellular pathway for conduction. Furthermore, the constitutive profile of connexin expression within the microcirculation is unknown. We tested the hypothesis that conducted vasodilation and connexin expression are intrinsic to the endothelium of arterioles (17 +/- 1 microm diameter) that supply the skeletal muscle fibers in the cremaster of anesthetized C57BL/6 mice. ACh delivered to an arteriole (500 ms, 1-microA pulse; 1-microm micropipette) produced local dilation of 17 +/- 1 microm; conducted vasodilation observed 1 mm upstream was 9 +/- 1 microm (n = 5). After light-dye treatment to selectively disrupt endothelium (250-microm segment centered 500 microm upstream, confirmed by loss of local response to ACh while constriction to phenylephrine and dilation to sodium nitroprusside remained intact), we found that conducted vasodilation was nearly abolished (2 +/- 1 microm; P < 0.05). Whole-mount immunohistochemistry for connexins revealed punctate labeling at borders of arteriolar endothelial cells, with connexin40 and connexin37 in all branches and connexin43 only in the largest branches. Immunoreactivity for connexins was not apparent in smooth muscle or in capillary or venular endothelium, despite robust immunolabeling for alpha-actin and platelet endothelial cell adhesion molecule-1, respectively. We conclude that vasodilation is conducted along the endothelium of mouse skeletal muscle arterioles and that connexin40 and connexin37 are the primary connexins forming gap junction channels between arteriolar endothelial cells.

Acetylcholine↗

Microvessels promote motor nerve survival and regeneration through local VEGF release following ectopic reattachment.

OBJECTIVES: Nerves and blood vessels form a close association during embryogenesis. Growth and guidance factors initially attributed to either nerves or vessels are now known to affect both tissues; prominent among these is vascular endothelial growth factor (VEGF). The authors investigated whether axons would associate with blood vessels in a regenerating system and questioned whether VEGF is integral to neurotization following axotomy. METHODS: In hamsters 8-12 weeks of age, the accessory nerve (CN XI) to the retractor muscle of the cheek pouch was cut and the proximal stump was reattached ectopically onto the muscle. Vascular casting and immunolabeling were used to quantify the extent of neurovascular association during regeneration. A role for VEGF was investigated using immunolocalization of VEGF and its receptor (sVEGFR2) as well as local sequestration of VEGF with soluble receptor (sVEGFR1). RESULTS: Regenerating axons aligned with microvessels of the vasa nervorum along a "chaperone" region during outgrowth from the reattachment site and while entering the muscle. In this approximately 1-mm region, VEGF protein was expressed by growing microvessels despite a approximately 50% reduction (p < .05) in total muscle VEGF concentration. VEGFR2 was expressed by regenerating axons and growth cones. Sequestration of VEGF by sVEGFR1 impaired neurotization by approximately 40% (p < .05). The chaperone region ended where regenerating microvessels anastomosed with the native microcirculation and their expression of VEGF protein diminished. CONCLUSIONS: Regenerating axons and blood vessels align during outgrowth from ectopic reattachment. This interaction dissipates as vascular anastomoses form with established microvessels and axons target muscle fibers. Local production of VEGF by growing microvessels supports motor nerve survival and regeneration.

Animals↗

Histamine inhibits conducted vasodilation through endothelium-derived NO production in arterioles of mouse skeletal muscle.

Conducted vasodilation along arterioles manifests the spread of hyperpolarization through gap junction channels along endothelium. Whereas histamine increases the permeability of capillary and venular endothelium, its effect on the integrity of arteriolar endothelium is unknown. We tested whether histamine could inhibit conducted vasodilation. In second-order arterioles (2A) supplying the cremaster muscle of C57BL6, PECAM-1-/-, and eNOS-/- mice (8-12 wk), neither resting (16+/-2 microm) nor maximal (38+/-2 microm) diameters were different. Acetylcholine (ACh) microiontophoresis (1 microA, 500 ms pulse) triggered vasodilation that was conducted >1400 microm along arterioles. Neither local (14+/-2 microm) nor conducted vasodilation (10+/-2 microm) was different among mice. Histamine (5 microM) had no effect on resting diameter or local vasodilation to ACh yet inhibited conduction by >50% in C57BL6 and PECAM-1-/- mice (P<0.05); this effect was abolished after blockade of NO synthase or of soluble guanylate cyclase. Washout of histamine restored conduction, though recovery was longer (P<0.05) in PECAM-1-/- mice vs. C57BL6 mice. Remarkably, conducted vasodilation in eNOS-/- mice was insensitive to histamine. These findings indicate that histamine inhibits cell-to-cell coupling through an NO-dependent mechanism and suggests a dynamic interaction among intercellular adhesion molecules and gap junction channels along arteriolar endothelium.

Acetylcholine↗

Neural control of muscle blood flow during exercise.

Activation of skeletal muscle fibers by somatic nerves results in vasodilation and functional hyperemia. Sympathetic nerve activity is integral to vasoconstriction and the maintenance of arterial blood pressure. Thus the interaction between somatic and sympathetic neuroeffector pathways underlies blood flow control to skeletal muscle during exercise. Muscle blood flow increases in proportion to the intensity of activity despite concomitant increases in sympathetic neural discharge to the active muscles, indicating a reduced responsiveness to sympathetic activation. However, increased sympathetic nerve activity can restrict blood flow to active muscles to maintain arterial blood pressure. In this brief review, we highlight recent advances in our understanding of the neural control of the circulation in exercising muscle by focusing on two main topics: 1) the role of motor unit recruitment and muscle fiber activation in generating vasodilator signals and 2) the nature of interaction between sympathetic vasoconstriction and functional vasodilation that occurs throughout the resistance network. Understanding how these control systems interact to govern muscle blood flow during exercise leads to a clear set of specific aims for future research.

Animals↗

Expression of homocellular and heterocellular gap junctions in hamster arterioles and feed arteries.

OBJECTIVES: Conduction of vasoconstrictor and vasodilator responses in the microcirculation involves electrical coupling through gap junction channels among cells of the vascular wall. The present study determined whether reported differences in the properties of conduction along the arterioles of the epithelial hamster cheek pouch (CPA) and feed arteries of its retractor skeletal muscle (RFA) result from differences in the expression profile of specific connexin (Cx) isoforms and the gap junctions they comprise. METHODS: Real-time PCR, immunohistochemistry and serial section electron microscopy were used to compare wall morphology and the distribution of gap junctions between respective vessels. RESULTS: Expression of mRNA for Cx37, 40, 43 and 45 was similar between CPA and RFA. In the endothelium, Cx37, 40 and 43 proteins were expressed abundantly between adjacent cells while Cx37 was present in the smooth muscle. In both vessels, endothelial and smooth muscle cell (SMC) layers were well connected by myoendothelial gap junctions (MEGJs), which were found near endothelial cell (EC) gap junctions. CONCLUSIONS: The absence of differential gap junctional expression between CPA and RFA, in spite of documented differences in cellular conduction pathways, supports the hypothesis that conductance of vascular gap junction channels can be differentially modulated in resistance microvessels.

Animals↗

Sympathetic nerves inhibit conducted vasodilatation along feed arteries during passive stretch of hamster skeletal muscle.

Ascending vasodilatation is integral to blood flow control in exercising skeletal muscle and is attributable to conduction from intramuscular arterioles into proximal feed arteries. Passive stretch of skeletal muscle can impair muscle blood flow but the mechanism is not well understood. We hypothesized that the conduction of vasodilatation along feed arteries can be modulated by changes in muscle length. In anaesthetized hamsters, acetylcholine (ACh) microiontophoresis triggered conducted vasodilatation along feed arteries (diameter, 50-70 microm) of the retractor muscle secured at 100 % resting length or stretched by 30 %. At 100 % length, ACh evoked local dilatation (> 30 microm) and this response conducted rapidly along the feed artery (14 +/- 1 microm dilatation at 1600 microm upstream). During muscle stretch, feed arteries constricted approximately 10 microm (P < 0.05) and local vasodilatation to ACh was maintained while conducted vasodilatation was reduced by half (P < 0.01). Resting diameter and conduction recovered upon restoring 100 % length. Sympathetic nerve stimulation (4-8 Hz) produced vasoconstriction and attenuated conduction in the manner observed during muscle stretch, as did noradrenaline or phenylephrine (10 nM). Inhibiting nitric oxide production (Nomega-nitro-L-arginine, 50 microM) produced similar vasoconstriction yet had no effect on conduction. Phentolamine, prazosin, or tetrodotoxin (1 microM) during muscle stretch abolished vasoconstriction and restored conduction. Inactivation of sensory nerves with capsaicin had no effect on vasomotor responses. Thus, muscle stretch can attenuate conducted vasodilatation by activating alpha-adrenoreceptors on feed arteries through noradrenaline released from perivascular sympathetic nerves. This autonomic feedback mechanism can restrict muscle blood flow during passive stretch.

Animals↗