Increase In Arteriolar Diameter Research Articles

Relation between retinal vessel diameter and posterior segment optical coherence tomography variables in middle-aged Caucasians: the Northern Finland Birth Cohort Eye Study

AimsStudying the relationship between retinal vessel diameter (RVD) with (1) macular thickness and volume, (2) retinal nerve fibre layer (RNFL), (3) ganglion cell-inner plexiform layer (GC-IPL) and (4) optic nerve...

Endogenous dipeptidyl peptidase IV modulates skeletal muscle arteriolar diameter in rats.

The purpose of this study is to investigate that dipeptidyl peptidase IV (DPP‐IV) released from skeletal and vascular smooth muscle can increase arteriolar diameter in a skeletal muscle vascular bed by reducing neuropeptide Y (NPY)‐mediated vasoconstriction. We hypothesized that the effect of myokine DPP‐IV would be greatest in the smallest and least in the largest arterioles. Eight male Sprague Dawley rats (age 7–9 weeks; mass, mean ± SD: 258 ± 41 g) were anesthetized and the gluteus maximus dissected in situ for intravital microscopy analysis of arteriolar diameter of the vascular network. Computational modeling was performed on the diameter measurements to evaluate the overall impact of diameter changes on network resistance and flow distribution. In the first set of experiments, whey protein isolate powder was added to physiological saline solution, put in a heated reservoir, and applied to the preparation to induce release of DPP‐IV from the muscle. This resulted in an order‐dependent increase in arteriolar diameter, with the largest change in the 6A arterioles (63% more reactive than 1A arterioles; P < 0.05). This effect was abolished by adding the DPP‐IV inhibitor, Diprotin A. To test if the DPP‐IV released was affecting NPY‐mediated vasoconstriction, we applied NPY and whey protein, which resulted in attenuated vasoconstriction. These findings suggest that DPP‐IV is released from muscle and has a unique effect on blood flow, which appears to act on NPY to attenuate vasoconstriction. The findings suggest that DPP‐IV released from the skeletal or smooth muscle can alter muscle blood flow.

Vasodilatory Effect of the Dissolved Glycine locally applied on Pial Microvessels

By the method of biomicroscopy it was shown that a single application of a dissolved glycine on the parietal region of the rat brain (“open window” technique) leads to a vasodilatation - an increase in arteriolar diameter about 1.5-2 times.

Novel Uses for Botulinum Neurotoxin in Upper Limb Surgery.

Novel Uses for Botulinum Neurotoxin in Upper Limb Surgery.

Influence of antiseptics on microcirculation after neuronal and receptor blockade

The topical application of the antiseptics octenidine and polyhexanide on wounds seems to improve microcirculation. These two antiseptics were tested in combination with neuronal inhibition and sympathethic receptor blockade to verify these findings, explore the influence of β blockers on these microcirculative effects, and find out the principle of operation. Investigations were carried out on a standardised cremaster muscle model in rats (n = 66). The tested antiseptics, octenidine and polyhexanide were investigated alone (n = 12) and in combination with bupivacaine (n = 12), metoprolol (n = 12), phentolamine (n = 12) and surgical denervation (n = 12). Physiological saline was used for control (n = 6). The arteriolar diameter and functional capillary density (FCD) were investigated via trans-illumination microscopy before, as well as 60 and 120 minutes after application. Polyhexanide caused a significant increase in arteriolar diameter (86·5 ± 3·8 µm versus 100·0 ± 3·6 µm) and, like octenidine (7·2 ± 0·7 n/0·22 mm(2) versus 11·6 ± 0·6 n/0·22 mm(2) ), in FCD (9·2 ± 0·5 versus 12·6 ± 0·9) as well. When the antiseptics are used in combination with bupivacaine, metoprolol, phentolamine or surgical sympathectomy, these effects were eliminated or inverted. Assessing the results of the different blockades in combination with polyhexanide, we surmise that the antiseptic polyhexanide acts on the microcirculation mainly by blocking α receptors. This study shows that polyhexanide and octenidine improve muscular perfusion. Interestingly, the benefit of polyhexanide and octenidine on muscular perfusion is eliminated when the antiseptics are combined with other vasoactive agents, especially β blockers.

Adipocyte-derived factor reduces vasodilatory capability in ob−/ob− mice

Obesity is associated with impaired functional hyperemic response. We have shown that ATP-sensitive potassium (K(ATP)) channels are important in mediating functional vasodilation. Adipocyte-derived factors (ADFs) can alter vascular tone via opening K(ATP) channels. We hypothesize that, in an animal model of obesity, ADFs will decrease basal arteriolar tone by opening K(ATP) channels, resulting in an attenuated functional vasodilation. We used wild-type (WT) mice and ob(-)/ob(-) mice (ob) to test this hypothesis. The spinotrapezius muscle was prepared for the microcirculatory observation of arcade arterioles, and we measured the vasodilatory responses to muscle stimulation. The basal arteriolar diameter was larger in ob mice compared with WT mice. The K(ATP) channel inhibitor glibenclamide (10 microM) decreased arteriolar diameter in ob mice with no effect in WT mice. The increase in arteriolar diameter induced by muscle stimulation was attenuated in ob mice compared with WT mice. To determine the mechanisms for the opening of K(ATP) channels, fat was collected from the ob mice, subcutaneous fat from around the spinotrapezius muscle (OBSF) or visceral fat (OBVF) and was incubated in physiological saline solution (PSS). The vasodilatory responses to the fat-conditioned PSS were determined in WT mice. Treatment with OBSF- or OBVF -conditioned PSS increased the arteriolar diameters in WT mice, a dilation that was inhibited by glibenclamide. The absolute diameters induced by muscle stimulation were not altered by the fat-conditioned PSS. These results suggest that, in ob mice, local ADFs reduce the functional vasodilatory capability via opening K(ATP) channels.

Microcirculatory Responses to Acupuncture Stimulation and Phototherapy

Acupuncture stimulation and phototherapy have been reported to have analgesic effects and improve the microcirculation. However, few studies have directly examined changes in peripheral blood vessels, either quantitatively or objectively. We assessed the responses of arteriolar blood flow to acupuncture stimulation and phototherapy under direct vision to examine the effects of these treatments. We used 40 rabbits with a rabbit ear chamber attached to the auricle. The rabbit ear chamber was fixed to the auricle under a dissecting microscope. Arterioles were selected and observed with the use of a microscope video camera. Pentobarbital was injected IV. The trachea was intubated and spontaneous respiration was maintained. Rabbits were randomly assigned to receive acupuncture stimulation (acupuncture group, n = 10), near-infrared lamp irradiation (lamp group, n = 10), near-infrared low-powered laser irradiation (laser group, n = 10), or no irradiation (control group, n = 10). In the acupuncture group, an acupuncture needle was placed in the auricle for 20 min. The lamp group repeatedly received 1 s of near infrared irradiation (1540 mW) followed by 4 s of treatment cessation. The laser group continuously received 60 mW of laser irradiation. In the lamp and laser groups, the auricle (same site as that of the acupuncture needles in the acupuncture group) was irradiated for 10 min with a contact probe. Arteriolar diameter and blood flow velocity were measured at baseline and for 60 min after acupuncture or irradiation treatment. Blood flow rate was calculated by multiplying the blood flow velocity by the cross-sectional area of the vessels. Arteriolar diameter significantly increased to 131% +/- 14% in the acupuncture group (P < 0.005), 129% +/- 19% in the lamp group (P < 0.005), and 128% +/- 11% in the laser group (P < 0.005) when compared with the pretreatment value (100%). Maximum values were reached 20 min after the end of the acupuncture stimulation, and 10 min after the end of lamp and laser irradiation. The three groups showed significant increases in arteriolar diameter when compared with the control group (P < 0.005). Blood flow velocity and blood flow rate showed similar trends to arteriolar diameter. Treatment effect persisted for 40-50 min after the end of stimulation and irradiation. Acupuncture stimulation and phototherapy were directly confirmed to increase the diameter and blood flow velocity of the peripheral arterioles. Acupuncture stimulation and phototherapy, associated with minimal systemic and local side effects, can enhance the microcirculation and may be a useful supportive treatment for diseases caused by poor peripheral blood flow.

Abnormal Responses of the Human Cerebral Microcirculation to Papaverin During Aneurysm Surgery

The role of the cerebral microcirculation in delayed ischemia after subarachnoid hemorrhage remains obscure. To test the hypothesis that cerebral arterioles have a reduced capacity to dilate after subarachnoid hemorrhage, we studied the microvascular responses to papaverine (PPV) in patients undergoing aneurysm surgery. Method- In 14 patients undergoing aneurysm surgery, the diameter changes of cortical microvessels after topical application of PPV were observed using orthogonal polarizing spectral imaging. In control subjects, neither arterioles nor venules showed diameter changes in response to topical PPV. In patients operated <48 hours after subarachnoid hemorrhage, PPV resulted in vasodilatation of arterioles with 45+/-41% increase in arteriolar diameter (P=0.012). In 2 of these patients, arteriolar diameter returned below baseline value. In patients undergoing late aneurysm clipping, the diameter increase of the arterioles after PPV was 25+/-24% (not significant). In 2 patients of this group, no vasodilatation but focal arteriolar narrowing occurred. In patients with subarachnoid hemorrhage, unpredictable response patterns to PPV were observed with "rebound" vasoconstriction suggesting increased contractility of the microcirculation. Yet, diminished vasodilatory capacity of the cerebral microcirculation after subarachnoid hemorrhage was not confirmed by this study.

Pial Microvascular Responses to Transient Bilateral Common Carotid Artery Occlusion: Effects of Hypertonic Glycerol

Objective: The aim of the study was to assess the rat pial microvessel alterations due to transient bilateral common carotid artery occlusion (BCCAO) and to investigate the mechanism of 10% hypertonic glycerol neuroprotection. Our suggestion was that 10% glycerol solution infusion could dilate pial arterioles through nitric oxide release and/or stimulation of ATP-sensitive potassium (K_ATP) channels. Therefore, we studied the effects of hypertonic glycerol after inhibition of nitric oxide synthase, with N^G-nitro-L-arginine-methyl ester or N^G-nitro-L-arginine, or K_ATP channels with glibenclamide. Methods: Pial microcirculation of male Wistar rats was visualized by a fluorescent microscopy technique through an open cranial window, using fluorescein isothiocyanate bound to dextran (molecular weight 70 kDa). BCCAO was induced for 30 min and reperfusion lasted 60 min. The arterioles were classified according to the Strahler ordering scheme. Permeability increase was quantified by normalized grey levels (NGL). Leucocytes were stained with rhodamine 6G. Perfused capillary length and capillary red blood cell (RBC) velocity were measured by computer-assisted methods. Results: The arterioles were assigned 5 orders of branchings, from order 1 (diameter 16.0 ± 2.5 µm) to order 5 (62.0 ± 5.0 µm). BCCAO caused inhomogenous changes in diameter of arterioles and leakage of fluorescent dextran, that was further enhanced by reperfusion (0.45 ± 0.05 NGL, p < 0.01). Adhesion of leukocytes to venules was marked and capillary perfusion was reduced by 39.2 ± 6.0% of baseline as well as capillary RBC velocity. 10% glycerol solution caused an increase in diameter of all arterioles within 25 ± 2 min of administration (by 20 ± 5% in order 4, 25 ± 4% in order 3 and 18 ± 3% in order 2; p < 0.01). Leakage (0.19 ± 0.03 NGL, p < 0.01), leukocyte adhesion (2.0 ± 1.0/100 µm of venular length, p < 0.01) and capillary occlusion (reduction by 13.0 ± 5.5% of baseline) were prevented compared with controls. Capillary RBC velocity increased compared with controls. N^G-nitro-L-arginine-methyl ester or N^G-nitro-L-arginine infused prior to glycerol caused vasoconstriction and reduced the protective effects of hypertonic glycerol on permeability increase. The number of adherent leukocytes and perfused capillary length decreased, while capillary RBC velocity was higher than baseline. Glibenclamide prior to 10% glycerol solution blunted glycerol-induced vasodilatation, but did not affect protection by hypertonic glycerol on blood-brain barrier disruption, leukocyte adhesion and capillary perfusion, preserving high capillary RBC velocity. Papaverine (20 mg/kg body weight) induced an increase in arteriolar diameter, enhancing interstitial edema; adhesion of leukocytes was marked as well as capillary occlusion, while capillary RBC velocity increased. Conclusions: 10% glycerol solution was able to prevent microvascular alterations due to BCCAO protecting cerebral tissue. The effects appear to be due to hyperosmolality causing stimulation of K_ATP channels, increase in vessel wall shear stress and release of nitric oxide.

The vasodilatory effect of juxta‐arteriolar microinjection of endothelin‐A receptor inhibitor in healthy and in acute branch retinal vein Occlusion Minipig Retinae

Abstract Purpose: To investigate the vasoactive effect of endothelin‐A receptor inhibitor BQ‐123 on the retinal arteriolar vasculature in normal and in acute branch retinal vein occlusion (BRVO) minipig retinae. Methods: Under general anesthesia, 6 normal eyes of 6 minipigs and 5 eyes of 5 minipigs with acute experimental BRVO were evaluated. In all eyes, a slow, continuous microinjection of 30 μl BQ‐123 (0.67 μg/ml) was performed 50 to 100 μm away from a retinal arteriole, avoiding exerting pressure on retina’s anatomic structures. After the microinjection, the retinae were observed for changes in vessels’ diameter. The procedure was recorded in real time. Throughout the procedure, the animals’ vital signs were monitored. Results: Overall (n=11), an increase of 18.56% and 26.45% in arteriolar diameter was evidenced 5 and 15 minutes respectively after BQ‐123 microinjection. When separately examining normal (n=6) versus OBVR (n=5) eyes, the increase in arteriolar diameter 5 minutes post injection was 16.75% versus 19.86% respectively (P=0.491), whereas the increase in arteriolar diameter 15 minutes post injection was 25.14% versus 27.4% (P=0.591). Conclusions: Our results demonstrate a significant increase in retinal arteriolar diameter after juxta‐arteriolar BQ‐123 microinjection, both in healthy and in acute OBVR retinae. There was no statistically significant difference between the amount of vasodilation exerted by BQ‐123 on healthy and on BRVO retinae. This vasodilatory effect may be beneficial in counterbalancing or reversing the arteriolar vasoconstriction that settles within hours following BRVO, with subsequent improvement of arteriolar blood flow.

Retinal vessel diameter and cardiovascular mortality: pooled data analysis from two older populations

The retinal microvasculature may reflect pre-clinical changes in the cerebral and coronary microcirculations. We assessed whether smaller retinal arterioles and larger venules predicted coronary heart disease (CHD)- and stroke-mortality. We pooled data from the Beaver Dam Eye Study (n = 4926, aged 43-86) and the Blue Mountains Eye Study (n = 3654, aged 49-97). Retinal vessel diameters were measured from digitized retinal photographs. Change point models were used to assess and document the existence of threshold effects. We defined smaller arterioles as diameters within the narrowest quintile and larger venules as diameters within the widest quintile, with other quintiles as the reference. Of 8550 participants, 7494 (88%) with complete data were included, of whom 653 died from CHD and 299 from stroke over 10-12 years follow-up. After multivariable adjustment, each standard deviation (SD) increase in arteriolar diameter, or SD decrease in venular diameter, was not found to be significantly associated with either CHD-mortality or stroke-mortality. However, smaller arterioles [hazard ratio (HR) 1.34, 95% confidence interval (CI) 1.11-1.62] and larger venules (HR 1.24, CI 1.02-1.52), predicted increased risk of CHD-mortality. These associations were mainly evident among persons aged 43-69 (smaller arterioles: HR 1.70, CI 1.27-2.28; larger venules: HR 1.41, CI 1.06-1.89). Smaller arterioles (HR 1.64, CI 1.00-2.67) and larger venules (HR 1.53, CI 0.94-2.47) were also associated with an increased risk of stroke-mortality among persons aged 43-69. Retinal vessel diameter may predict risk of CHD and stroke deaths in middle-aged persons.

Time-Dependent Alterations in Functional and Pharmacological Arteriolar Reactivity After Subarachnoid Hemorrhage

Disturbances in cerebral arteriolar function, in addition to large vessel vasospasm, may be responsible for ischemia after subarachnoid hemorrhage. The purpose of this study was to test the hypothesis that subarachnoid hemorrhage alters cerebral microvascular reactivity. An endovascular filament model was used to induce subarachnoid hemorrhage in halothane-anesthetized male Sprague-Dawley rats. We evaluated pial arteriolar responses to sciatic nerve stimulation, topically applied vasoactive agents (adenosine or sodium nitroprusside), and CO(2) inhalation in rats subjected to subarachnoid hemorrhage at 1 to 5 days after insult. In sham-operated rats, sciatic nerve stimulation evoked a 23.5+/-1.8% increase in arteriolar diameter, which was significantly attenuated to 13.7+/-0.9%, 12.8+/-2.5%, and 18.8+/-2.9% at 24, 48, and 72 hours after subarachnoid hemorrhage, respectively (P<0.05; n> or =7). At 96 and 120 hours after subarachnoid hemorrhage, sciatic nerve stimulation-induced dilation recovered to sham levels. Somatosensory-evoked potentials were unaltered by subarachnoid hemorrhage. Pial vasodilatation to adenosine (10 micromol/L) and sodium nitroprusside (1 micromol/L) were significantly impaired, by 47% and 41%, respectively, at 48 hours after subarachnoid hemorrhage (P<0.05; n=7). In contrast, CO(2) reactivity was unaffected by subarachnoid hemorrhage. Pial arteriolar responses to cortical activation may be decreased in the initial 2 to 3 days after experimental subarachnoid hemorrhage.

Microvascular Diameter Responses to the Controlled Release of Platelet Derived Growth Factor‐BB (PDGF‐BB) and Transforming Growth Factor‐β1 (TGF‐β1)

PDGF-BB, a smooth muscle cell (SMC) chemoattractant and mitogen, and TGF-β1, a SMC differentiation factor, may have utility as therapeutic arteriogenesis factors. However, few studies have examined whether the controlled release of PDGF-BB or TGF-β1 can amplify arteriogenesis. To this end, we utilized the mouse dorsal skinfold window chamber model, which allows for repeated vessel measurements over time and naturally exhibits arteriolar and venular structural lumen expansion. An 85:15 poly(DL-lactide-co-glycolide) microsphere containing either 0.2μg/mg PDGF-BB, 0.008μg/mg TGF-β1 or 4μg/mg BSA was inserted on Day 7. Microvascular diameter measurements were made at Days 7, 10 and 14 on individual vessels within the release profile of the microsphere (4mm) during topical superfusion of adenosine (10−4 M). Interestingly, PDGF-BB treatment elicited no change in arteriolar structural diameter [PDGF-BB: =25.0μm (48.0%) vs. BSA: =23.1μm (44.2%)], but a significant increase in venular structural diameter [PDGF-BB: =48.9μm (61.9%) vs. BSA: =14.2μm (18.2%)]. TGF-β1 treatment significantly attenuated normal arteriolar [TGFβ1: =7.8μm (17.1%) vs. BSA: =23.1μm (44.2%)] and venular [TGF-β1: =−14.4μm (−1.2%) vs. BSA: =14.2μm (18.2%)] structural lumen expansion. Because PDGF-BB elicited no further increase in arteriolar diameter and TGF-β1 caused vessel constriction, our results do not support the therapeutic potential of these factors. However, the mechanisms of these diameter responses remain unknown, and alterations in growth factor concentration and/or release kinetics may be needed to show efficacy. Supported by NIH HL65958.

Effects of centrally acting antihypertensive drugs on the microcirculation of spontaneously hypertensive rats.

We investigated the acute effects of centrally acting antihypertensive drugs on the microcirculation of pentobarbital-anesthetized spontaneously hypertensive rats (SHR). The effects of the sympatho-inhibitory agents clonidine and rilmenidine, known to activate both alpha2-adrenoceptors and nonadrenergic I1-imidazoline binding sites (I1BS) in the central nervous system, were compared to those of dicyclopropylmethyl-(4,5-dimethyl-4,5-dihydro-3H-pyrrol-2-yl)-amine hydrochloride (LNP 509), which selectively binds to the I1BS. Terminal mesenteric arterioles were observed by intravital microscopy. Activation of the central sympathetic system with L-glutamate (125 microg, ic) induced marked vasoconstriction of the mesenteric microcirculation (27 +/- 3%; N = 6, P < 0.05). In contrast, the marked hypotensive and bradycardic effects elicited by intracisternal injection of clonidine (1 microg), rilmenidine (7 microg) and LNP 509 (60 microg) were accompanied by significant increases in arteriolar diameter (12 +/- 1, 25 +/- 10 and 21 +/- 4%, respectively; N = 6, P < 0.05). The vasodilating effects of rilmenidine and LNP 509 were two-fold higher than those of clonidine, although they induced an identical hypotensive effect. Central sympathetic inhibition elicited by baclofen (1 microg, ic), a GABA B receptor agonist, also resulted in vasodilation of the SHR microvessels. The acute administration of clonidine, rilmenidine and LNP 509 also induced a significant decrease of cardiac output, whereas a decrease in systemic vascular resistance was observed only after rilmenidine and LNP 509. We conclude that the normalization of blood pressure in SHR induced by centrally acting antihypertensive agents is paralleled by important vasodilation of the mesenteric microcirculation. This effect is more pronounced with substances acting preferentially (rilmenidine) or exclusively (LNP 509) upon I1BS than with those presenting important alpha2-adrenergic activity (clonidine).

Adenosine’s role in hypercapnia-evoked cerebral vasodilation in the rat

Carbon dioxide induces a rapid dilation of cerebral arterioles, enabling local blood flow to match increasing metabolic requirements of tissue. Amongst the vasodilatory substances released by cortical tissue in response to CO 2 are adenosine and nitric oxide. Here we report that selective adenosine A 2A receptor antagonists, applied topically using a rat cortical window technique, significantly depressed the CO 2-evoked increase in arteriolar diameter, measured using video microscopy, as well as attenuating the CO 2 and pH reactivity of the cortical arterioles. Two non-selective inhibitors of nitric oxide synthase also significantly depressed the hypercapnia-evoked increase in arteriolar diameter.

Cerebrovascular response to decreased hematocrit: effect of cell-free hemoglobin, plasma viscosity, and CO2.

The effect of transfusing a nonextravasating, zero-link polymer of cell-free hemoglobin on pial arteriolar diameter, cerebral blood flow (CBF), and O2 transport (CBF x arterial O2 content) was compared with that of transfusing an albumin solution at equivalent reductions in hematocrit (approximately 19%) in anesthetized cats. The influence of viscosity was assessed by coinfusion of a high-viscosity solution of polyvinylpyrrolidone (PVP), which increased plasma viscosity two- to threefold. Exchange transfusion of a 5% albumin solution resulted in pial arteriolar dilation, increased CBF, and unchanged O2 transport, whereas there were no significant changes over time in a control group. Exchange transfusion of a 12% polymeric hemoglobin solution resulted in pial arteriolar constriction and unchanged CBF and O2 transport. Coinfusion of PVP with albumin produced pial arteriolar dilation that was similar to that obtained with transfusion of albumin alone. In contrast, coinfusion of PVP with hemoglobin converted the constrictor response to a dilator response that prevented a decrease in CBF. Pial arteriolar dilation to hypercapnia was unimpaired in groups transfused with albumin or hemoglobin alone but was attenuated in the largest vessels in albumin and hemoglobin groups coinfused with PVP. Unexpectedly, hypocapnic vasoconstriction was blunted in all groups after transfusion of albumin or hemoglobin alone or with PVP. We conclude that 1) the increase in arteriolar diameter after albumin transfusion represents a compensatory response that prevents decreased O2 transport at reduced O2-carrying capacity, 2) the decrease in diameter associated with near-normal O2-carrying capacity after cell-free polymeric hemoglobin transfusion represents a compensatory mechanism that prevents increased O2 transport at reduced blood viscosity, 3) pial arterioles are capable of dilating to an increase in plasma viscosity when hemoglobin is present in the plasma, 4) decreasing hematocrit does not impair pial arteriolar dilation to hypercapnia unless plasma viscosity is increased, and 5) pial arteriolar constriction to hypocapnia is impaired at reduced hematocrit independently of O2-carrying capacity.

Differential structural adaptation to haemodynamics along single rat cremaster arterioles.

We tested the hypothesis that under physiological conditions, arterioles match their diameter to the level of shear stress. Haemodynamic and anatomical data were obtained in segments of the first-order arteriole of the rat cremaster muscle. Along this segment of ~10 mm in length, local blood pressure decreased from 68 +/- 4 mmHg upstream to 54 +/- 3 mmHg downstream (n = 5). Pulse pressure decreased from 8.2 +/- 1.3 mmHg upstream to 4.1 +/- 0.6 mmHg downstream. At the same locations, an increase in arteriolar diameter was measured in vivo, from 179 +/- 4 microm upstream to 203 +/- 4 microm downstream (n = 10). In vitro pressure-diameter relations of maximally dilated vessels showed that the passive diameter was larger in downstream than upstream segments over a 15-125 mmHg pressure range (n = 18). The wall stress was similar for the upstream vs. downstream location: 266 +/- 16 vs. 260 +/- 14 mN mm-2. However, shear stress decreased from 30 +/- 5 to 21 +/- 5 dyn cm-2 (3.0 +/- 0.5 to 2.1 +/- 0.5 N m-2; n = 4) along the artery. In conclusion, these results demonstrate that shear stress is not the only factor in determining vascular calibre. We suggest that arteriolar calibre may rather depend on an interplay between shear stress and the local pressure profile.

Electro-acupuncture stimulation to muscle afferents in anesthetized rats modulates the blood flow to the knee joint through autonomic reflexes and nitric oxide

Recent reports have focused on the mechanisms of the action of electro-acupuncture stimulation (EAS) in the regulation of blood flow to different tissues. In the knee joint, blood flow is known to be modulated mainly by sympathetic postganglionic fibers, but recently the release or induction of nitric oxide (NO) synthesis in response to electrical stimulation has also been suggested. Therefore, a direct observation of the microcirculation is needed to further understand the mechanism by which blood flow is regulated by somatic afferent stimulation. In the present study, the effects of EAS to the vastus medialis muscle on systemic hemodynamics and the knee joint microcirculation were observed in vivo using a real-time confocal laser-scanning microscope system (CLMS). Electrical stimulation (5 mA, 0.5 ms, 5 Hz) was applied for 30 min using a pair of acupuncture needles introduced into the vastus medialis muscle. To clarify a plausible involvement of NO in the responses to EAS, the stimulus was applied either in the presence or absence of N ω-nitro-L-arginine methyl ester (L-NAME). Stimulation to either the muscle or the skin of the thigh after blockade of neuromuscular transmission was performed to determine the involvement of muscle contraction during EAS treatment. The changes in mean arterial pressure (MAP) and diameter of the arterioles supplying the knee joint were monitored continuously until 60 min poststimulus. Significant and persistent increases in arteriolar diameter by 26±6% and MAP by 17±2%, respectively, were observed after EAS to the muscle. Electro-acupuncture to the vastus medialis in the presence of L-NAME produced a strong decrease in diameter of the knee joint arterioles by −38±14% under the baseline with a simultaneous increase of 35±5% in MAP. EAS to the skin did not produce changes in arteriolar diameter while a slight increase in MAP by 12±6% over the baseline occurred after the stimulus. EAS to the muscle after neuromuscular blockade did not produce significant changes in diameter, while an increase in MAP by 24±8% was still observed, which facts suggest that the muscle contraction is required to produce vasodilatation. These responses suggest that a dynamic balance between the autonomic nervous system and the release of NO is the primary mechanism mediating the EAS effects on knee joint microcirculation.

Albumin therapy of transient focal cerebral ischemia: in vivo analysis of dynamic microvascular responses.

To study whether intravascular or hemodynamic factors contribute to the marked neuroprotective effect of albumin therapy in focal cerebral ischemia, 2 complementary methods were applied: laser-scanning confocal microscopy (LSCM) and laser-Doppler perfusion imaging (LDPI). In the LSCM study, Sprague-Dawley rats were anesthetized with halothane/nitrous oxide, and a cranial window was placed over the dorsolateral frontoparietal cortex. Rats received 2-hour middle cerebral artery occlusion (MCAO) by an intraluminal suture and were treated with human albumin (1.25 g/kg; n=4) or saline (n=3) after 30 minutes of recirculation. Video images of cortical vessels were continually acquired and were digitized offline to measure diameters and fluorescent erythrocyte velocities. In the LDPI study, cortical perfusion was measured in anesthetized Sprague-Dawley rats that received 2-hour MCAO and were treated with albumin (2.5 g/kg; n=6) or saline (n=5) at 30 minutes after recirculation. In the LSCM study, MCAO was associated with arteriolar dilation and slowing of capillary and venular erythrocyte perfusion. During the first 15 to 30 minutes of postischemic recirculation, prominent foci of vascular stagnation developed within cortical venules, associated with thrombuslike foci and adherent corpuscular structures consistent in size with neutrophils. Saline administration failed to affect these phenomena, while albumin therapy was followed by significant increases in arteriolar diameter ( approximately 12%; P=0.007) and by a prompt improvement of venular and capillary erythrocyte perfusion and a partial disappearance of adherent thrombotic material. Albumin therapy increased erythrocyte flow velocity in both capillaries (288+/-73% versus 76+/-18% in the saline group; P=0.023) and venules (2.7-fold [P=0.001] versus 1.0-fold in the saline group [P=NS]). In the LDPI study, cortical perfusion declined during MCAO and rose initially with recirculation (to approximately 135% of baseline) in both groups. Mean cortical perfusion improved slightly (approximately 14%; P=NS) in albumin-treated animals. These results reveal a beneficial effect of albumin therapy in reversing stagnation, thrombosis, and corpuscular adherence within cortical venules in the reperfusion phase after focal ischemia and support its utility in the treatment of acute ischemic stroke.

Beta-Adrenoceptor and nNOS-derived NO interactions modulate hypoglycemic pial arteriolar dilation in rats.

We examined the relative contributions from nitric oxide (NO) and catecholaminergic pathways in promoting cerebral arteriolar dilation during hypoglycemia (plasma glucose congruent with 1.4 mM). To that end, we monitored the effects of beta-adrenoceptor (beta-AR) blockade with propranolol (Pro, 1.5 mg/kg iv), neuronal nitric oxide synthase (nNOS) inhibition with 7-nitroindazole (7-NI, 40 mg/kg ip) or ARR-17477 (300 microM, via topical application), or combined intravenous Pro + 7-NI or ARR-17477 on pial arteriolar diameter changes in anesthetized rats subjected to insulin-induced hypoglycemia. Additional experiments, employing topically applied TTX (1 microM), addressed the possibility that the pial arteriolar response to hypoglycemia required neuronal transmission. Separately, Pro and 7-NI elicited modest but statistically insignificant 10-20% reductions in the normal ~40% increase in arteriolar diameter accompanying hypoglycemia. However, combined Pro-7-NI was accompanied by a >80% reduction in the hypoglycemia-induced dilation. On the other hand, the combination of intravenous Pro and topical ARR-17477 did not affect the hypoglycemia response. In the presence of TTX, the pial arteriolar response to hypoglycemia was lost completely. These results suggest that 1) beta-ARs and nNOS-derived NO interact in contributing to hypoglycemia-induced pial arteriolar dilation; 2) the interaction does not occur in the vicinity of the arteriole; and 3) the vasodilating signal is transmitted via a neuronal pathway.