Dynamic in vivo measurement of erythrocyte velocity and flow in capillaries and of microvessel diameter in the rat brain by confocal laser microscopy.
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A new method for studying brain microcirculation is described. Both fluorescently labeled erythrocytes and plasma were visualized on-line through a closed cranial window in anesthetized rats, using laser-scanning two-dimension confocal microscopy. Video images of capillaries, arterioles, and venules were digitized off-line to measure microvessel diameter and labeled erythrocyte flow and velocity in parenchymal capillaries up to 200 microm beneath the brain surface. The method was used to analyze the rapid adaptation of microcirculation to a brief decrease in perfusion pressure. Twenty-second periods of forebrain ischemia were induced using the tour-vessel occlusion model in eight rats. EEG, arterial blood pressure, and body temperature were continuously controlled. In all conditions, labeled erythrocyte flow and velocity were both very heterogeneous in capillaries. During ischemia, capillary perfusion was close to 0, but a low blood flow persisted in arterioles and venules, while EEG was flattening. The arteriole and venule diameter did not significantly change. At the unclamping of carotid arteries, there was an instantaneous increase (by about 150%) of arteriole diameter. Capillary erythrocyte flow and velocity increased within 5 seconds, up to, respectively, 346 +/- 229% and 233 +/- 156% of their basal value. No capillary recruitment of erythrocytes was detected. All variables returned to their basal levels within less than 100 seconds after declamping. The data are discussed in terms of a possible involvement of shear stress in the reperfusion period. (+info)
Effects of chronic heparin administration on coronary vascular adaptation to hypertension and ventricular hypertrophy in sheep.
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BACKGROUND: Hypertension decreases myocardial perfusion capacity in adults for several reasons, including insufficient coronary angiogenesis with left ventricular (LV) hypertrophy, arteriolar hypertrophy, and altered vasomotion. Heparin influences growth factors that promote angiogenesis and vasodilation and inhibit arteriolar wall thickening. METHODS AND RESULTS: Adult sheep were given heparin 200 U/kg body wt SC twice daily throughout 6 weeks of LV and coronary hypertension from a progressively constricted ascending aortic band (n=14). They were compared with untreated sheep with (n=13) and without (n=13) aortic stenosis. After 6 weeks, maximum myocardial perfusion was measured during adenosine infusion in the conscious state by the microsphere method. Sheep with aortic stenosis had less maximum coronary flow per gram, less conductance reserve, and thicker arteriolar walls in the LV and nonhypertrophied right ventricle. Capillary density decreased in the LV endomyocardium and remained unchanged in the right ventricle. Heparin-treated sheep had significant partial normalization of coronary conductance reserve and maximum perfusion in both ventricles and capillary density in the LV endomyocardium. Arteriolar wall thickness was unchanged. Compared with untreated sheep with aortic stenosis, in heparin-treated sheep LV FGF-2 protein increased 2-fold, whereas FGF-2 mRNA remained unchanged. VEGF mRNA and protein increased 3-fold and 1.4-fold, respectively, whereas TGF-beta(1) mRNA declined 3-fold. CONCLUSIONS: Heparin administration during LV hypertension increases heparin-binding angiogenic factors FGF-2 and VEGF in the LV and ameliorates decreases in LV perfusion capacity and capillary density. (+info)
Effects of low doses of endothelin-1 on basal vascular tone and autoregulatory vasodilation in canine coronary microcirculation in vivo.
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The plasma level of endothelin-1 (ET-1) increases in several cardiovascular disorders. The present study examined whether threshold doses of ET-1 affect vascular tone and autoregulatory vasodilation during a reduction in perfusion pressure in the coronary microcirculation in vivo. In anesthetized open-chest dogs, arterial microvessels in the epimyocardium were observed through a microscope equipped with a floating objective. In 6 dogs, ET-1 (10(-13) to 10(-8)mol/L) was superfused onto the epimyocardium in a cumulative fashion. In another set of dogs (n= 16), the perfusion pressure of the observed vascular bed was reduced to 60 mmHg (mild stenosis) and to 40 mmHg (severe stenosis) by a hydraulic occluder, and the microvascular responses were observed in the presence (n=9) or absence (n=7) of ET-1 (10(-12) or 10(-11) mol/L). ET-1 > or =10(-11) mol/L constricted coronary arterioles (< or =100 microm in diameter) and small arteries (>100 microm in diameter) in a dose-dependent fashion. ET-1 of 10(-12) mol/L affected neither the basal diameters nor the dilation of vessels during the pressure reduction. ET-1 of 10(-11) mol/L decreased the diameters of arterioles and small arteries before and during the mild and severe stenosis. However, ET-1 did not attenuate the percentage dilation of arterioles from the baseline in response to the mild and severe stenosis. The data indicates the following: (1) ET-1 at doses > or =10(-11) mol/L similarly constricts coronary arterioles and small arteries; (2) ET-1 at 10(-11) mol/L, which is slightly higher than the pathophysiological plasma level, increases the basal vascular tone, but does not attenuate the autoregulatory vasodilation of the coronary microcirculation. (+info)
Microcirculatory basis for nonuniform flow delivery with intravenous nitroprusside.
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BACKGROUND: The purpose of this study was to determine the effects of systemic infusions of nitroglycerin and sodium nitroprusside on flow distribution and wall shear stress in the microcirculation. METHODS: With university approval, the cremaster muscle of 28 anesthetized (70 mg/kg pentobarbital given intraperitoneally) hamsters (Harlan Sprague Dawley: Syrian; weight, 121+/-11 g [mean +/- SDD) was observed using in vivo fluorescence microscopy. Arteriolar diameter, erythrocyte flux, and velocity were measured for a feed arteriole and its sequential branches. Observations were made during control (mean arterial pressure, 88+/-4 mm Hg) and after 30 min of intravenous delivery of sodium nitroprusside or nitroglycerin, titrated to decrease mean arterial pressure by 20 mm Hg. RESULTS: Sodium nitroprusside significantly dilated select upstream portions of the network (23+/-2.6 to 29+/-2.6 microm); no arterioles were dilated with nitroglycerin. Erythrocyte flux into the feed (i.e., inflow into the arteriolar network) and into the sequential branches (i.e., distribution within the network) were evaluated. With nitroglycerin, inflow decreased significantly from 1,560+/-335 to 855+/-171 cells/s, and flux into the branches decreased evenly. With sodium nitroprusside, inflow increased significantly to 2,600+/-918 cells/s, yet cells were "stolen" from upstream branches (a decrease from 425+/-67 to 309+/-87 cells/s in the first branch). Excess flow passed into a downstream "thorough-fare channel," significantly increasing flux from 347+/-111 to 761+/-246 cells/s. Wall shear stress decreased uniformly with nitroglycerin infusion, with a decrease in the feed from 8.8+/-2.5 to 6+/-1.7 dyn/cm2. With sodium nitroprusside, variable changes occurred that were location specific within the network. For instance, at the inflow point to the network, wall shear stress changed from 8.3+/-2.5 to 4.2+/-3.3 dyn/cm2. CONCLUSIONS: Nitroglycerin infusion promoted homogeneity of flow. Sodium nitroprusside significantly increased the heterogeneity of flow within this arteriolar network; an anatomic location for steal induced by sodium nitroprusside is identified. (+info)
The incidence and development of periarteritis nodosa in testicular arterioles and mesenteric arteries of spontaneously hypertensive rats.
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We sought to clarify the incidence, vessel-size and age distribution of periarteritis nodosa in rats occurring as a vascular lesion in malignant hypertension. Stroke-prone spontaneously hypertensive and stroke-resistant spontaneously hypertensive rat strains were studied, as well as Wistar-Kyoto control rats. Mesenteric arteries and testicular arteries were examined histologically. Additionally, electron microscopy investigation was carried out on one stroke-prone hypertensive rat and one control. Periarteritis nodosa lesions were present in testicular arterioles in 57.1%, and mesenteric arteries in 28.6%, of stroke-prone hypertensive rats aged 9.5 mo. Lesion incidence at these sites was 100% and 60% respectively in 10 stroke-prone rats aged 15.5 mo, and 42.9% and 28.6% in stroke-resistant hypertensive rats aged 22.5 mo. In contrast, the incidence rate was 0% at both sites in stroke-resistant hypertensive rats aged 8 or 14.5 mo, and in control rats aged 9.5 or 25 mo. In stroke-prone rats, arteritis lesion counts (mean+/-SD) in testicular sections were 11.6+/-17 at age 9.5 mo and 96.3+/-60.9 at age 15.5 mo. In individual lesion scoring, arteritis was more severe in mesenteric arteries than in testicular arterioles. For arteriolar lesion distribution patterns in testicular sections, partial peripheral, partial peripheral plus central, and circumferential patterns were all noted. In conclusion, periarteritis nodosa in hypertensive stroke-prone rats occurs earlier in testicular arterioles, but attains greater severity in the mesenteric artery. (+info)
cAMP-independent dilation of coronary arterioles to adenosine : role of nitric oxide, G proteins, and K(ATP) channels.
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Adenosine is known to play an important role in the regulation of coronary blood flow during metabolic stress. However, there is sparse information on the mechanism of adenosine-induced dilation at the microcirculatory levels. In the present study, we examined the role of endothelial nitric oxide (NO), G proteins, cyclic nucleotides, and potassium channels in coronary arteriolar dilation to adenosine. Pig subepicardial coronary arterioles (50 to 100 microm in diameter) were isolated, cannulated, and pressurized to 60 cm H(2)O without flow for in vitro study. The arterioles developed basal tone and dilated dose dependently to adenosine. Disruption of endothelium, blocking of endothelial ATP-sensitive potassium (K(ATP)) channels by glibenclamide, and inhibition of NO synthase by N(G)-nitro-L-arginine methyl ester and of soluble guanylyl cyclase by 1H-[1,2,4]oxadiazolo[4,3,-a]quinoxalin-1-one produced identical attenuation of vasodilation to adenosine. Combined administration of these inhibitors did not further attenuate the vasodilatory response. Production of NO from coronary arterioles was significantly increased by adenosine. Pertussis toxin, but not cholera toxin, significantly inhibited vasodilation to adenosine, and this inhibitory effect was only evident in vessels with an intact endothelium. Tetraethylammonium, glibenclamide, and a high concentration of extraluminal KCl abolished vasodilation of denuded vessels to adenosine; however, inhibition of calcium-activated potassium channels by iberiotoxin had no effect on this dilation. Rp-8-Br-cAMPS, a cAMP antagonist, inhibited vasodilation to cAMP analog 8-Br-cAMP but failed to block adenosine-induced dilation. Furthermore, vasodilations to 8-Br-cAMP and sodium nitroprusside were not inhibited by glibenclamide, indicating that cAMP- and cGMP-induced dilations are not mediated by the activation of K(ATP) channels. These results suggest that adenosine activates both endothelial and smooth muscle pathways to exert its vasodilatory function. On one hand, adenosine opens endothelial K(ATP) channels through activation of pertussis toxin-sensitive G proteins. This signaling leads to the production and release of NO, which subsequently activates smooth muscle soluble guanylyl cyclase for vasodilation. On the other hand, adenosine activates smooth muscle K(ATP) channels and leads to vasodilation through hyperpolarization. It appears that the latter vasodilatory process is independent of G proteins and of cAMP/cGMP pathways. (+info)
NO mediates postjunctional inhibitory effect of neurogenic ACh in guinea pig small intestinal microcirculation.
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The present study was designed to evaluate the role of the endothelium as an effector organ of neurally mediated inhibition of vascular tone. Acetylcholine (ACh), either released by stimulation of the submucosal ganglia or applied exogenously, inhibited phenylephrine (PE)-induced constrictions in arterioles of the guinea pig intestinal submucosa. N(G)-monomethyl-L-arginine (L-NMMA), an inhibitor of nitric oxide (NO) synthesis, attenuated the response to superfused ACh by 74% compared with 94% attenuation obtained with N(G)-nitro-L-arginine (L-NNA). L-NNA attenuated the response to neurally released ACh by 98% and that to iontophoretically applied ACh by 92%. L-Arginine reversed the effects of both L-NMMA and L-NNA. Functional integrity of the endothelium was essential for the neurally mediated inhibition of PE-induced constrictions. However, neurogenic inhibition of neurally evoked constrictions was preserved despite endothelial disruption. It was concluded that at the postjunctional level, the mechanism of action of neurally released ACh was almost exclusively via a NO-dependent pathway, with the source of NO being the vascular endothelium. (+info)
Cerebrovascular reactivity to CO(2) and hypotension after mild cortical impact injury.
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Cerebrovascular reactivity to CO(2) or hypotension was studied in vivo and in vitro [pressurized arteries ( approximately 82 micrometer) and arterioles ( approximately 30 micrometer)] at 1 h after mild controlled cortical impact (CCI) injury in rats. The cortical perfusion response [assessed using laser-Doppler flowmetry (LDF)] to altered CO(2) was diminished (up to 81%) after mild CCI injury. The responses to CO(2) alterations in arteries and arterioles isolated from the injured cortex were similar to responses in vessels isolated from sham-injured animals. After mild CCI injury, the autoregulatory response to hypotension (measured using LDF) was maintained or even enhanced, depending on the method used to measure the response. Vessels isolated from the injury site showed a response to changes in pressure similar to that in vessels isolated from sham-injured rats. We conclude that mild CCI injury produces complicated alterations in cerebrovascular control. Whereas the autoregulatory response to hypotension was maintained or even enhanced, the in vivo vascular response to CO(2) was severely compromised. The altered response to CO(2) was not caused by an intrinsic vascular perturbation but rather an altered milieu after mild CCI injury. (+info)