Shear stress-induced vasodilation in porcine coronary conduit arteries is independent of nitric oxide release

The present study was performed to determine the importance of nitric oxide in eliciting epicardial coronary artery dilation during sustained increases in shear stress in the absence of pulsatile flow. Isolated first-order porcine epicardial coronary conduit arteries (approximately 500 microm) were preconstricted (U-46619) and subjected to steady-state changes in flow in vitro. Nonpulsatile flow (shear stress range from 0 to approximately 100 dyn/cm2) produced a graded dilation of epicardial arteries. Inhibiting nitric oxide synthase with 10(-5) M N(omega)-nitro-L-arginine methyl ester (L-NAME) blocked bradykinin-induced vasodilation but did not affect the flow-diameter relation or the maximum change in diameter from static conditions (67 +/- 10 microm in control vs. 71 +/- 8 microm after L-NAME, P = not significant). The addition of indomethacin (10(-5) M) had no effect on flow-mediated vasodilation. Depolarizing vascular smooth muscle with KCl (60 mM) or removing the endothelium blocked bradykinin vasodilation and completely abolished flow-mediated responses. The K+ channel blocker tetraethylammonium chloride (TEA; 10(-4)M) attenuated flow-mediated vasodilation (maximum diameter change was 110 +/- 18 microm under control conditions vs. 58 +/- 10 microm after TEA, P < 0.001). These data indicate that epicardial coronary arteries dilate to steady-state changes in nonpulsatile flow via a mechanism that is independent of nitric oxide production. The ability to completely block this with KCl and attenuate it with TEA supports the hypothesis that epicardial coronary arteries dilate to steady levels of shear stress through hyperpolarization of vascular smooth muscle. This may be secondary to the release of an endothelium-dependent hyperpolarizing factor.     

Role of hyaluronic acid glycosaminoglycans in shear-induced endothelium-derived nitric oxide release

Endothelium-derived nitric oxide (NO) is synthesized in response to chemical and physical stimuli. Here, we investigated a possible role of the endothelial cell glycocalyx as a biomechanical sensor that triggers endothelial NO production by transmitting flow-related shear forces to the endothelial membrane. Isolated canine femoral arteries were perfused with a Krebs-Henseleit solution at a wide range of perfusion rates with and without pretreatment with hyaluronidase to degrade hyaluronic acid glycosaminoglycans within the glycocalyx layer. NO production rate was evaluated as the product of nitrite concentration in the perfusate and steady-state perfusion rate. The slope that correlates the linear relation between perfusion rate and NO production rate was taken as a measure for flow-induced NO production. Hyaluronidase treatment significantly decreased flow-induced NO production to 19 +/- 9% of control (mean +/- SD; P < 0.0001 vs. control; n = 11), whereas it did not affect acetylcholine-induced NO production (88 +/- 17% of pretreatment level, P = not significant; n = 10). We conclude that hyaluronic acid glycosaminoglycans within the glycocalyx play a pivotal role in detecting and amplifying the shear force of flowing blood that triggers endothelium-derived NO production in isolated canine femoral arteries.     

Effects of luminal shear stress on cerebral arteries and arterioles

The effect of luminal shear stress was studied in cerebral arteries and arterioles. Middle cerebral arteries (MCA) and penetrating arterioles (PA) were isolated from male Long-Evans rats, mounted in a tissue bath, and pressurized. After the development of spontaneous tone, inside diameters were 186 +/- 5 microm (n = 28) for MCA and 65 +/- 3 microm (n = 37) for PA. MCA and PA constricted approximately 20% with increasing flow. Flow-induced constriction persisted in MCA and PA after removal of the endothelium. After removal of the endothelium, the luminal application of a polypeptide containing the Arg-Gly-Asp amino acid sequence (inhibitor of integrin attachment) abolished the flow-induced constriction. Similarly, an antibody specific for the beta(3)-chain of the integrin complex significantly inhibited the flow-induced constriction. The shear stress-induced constriction was accompanied by an increase in vascular smooth muscle Ca(2+). For example, a shear stress of 20 dyn/cm(2) constricted MCA 8% (n = 5) and increased Ca(2+) from 209 +/- 17 to 262 +/- 29 nM (n = 5). We conclude that isolated cerebral arteries and arterioles from the rat constrict to increased shear stress. Because the endothelium is not necessary for the response, the shear forces must be transmitted across the endothelium, presumably by the cytoskeletal matrix, to elicit constriction. Integrins containing the beta(3)-chain are involved with the shear stress-induced constrictions.     

Tracheal blood flow and luminal clearance of 99mTc-DTPA in sheep.

Tracheal blood flow and 99mTc-labeled diethylenetriamine pentaacetic acid (DTPA) clearance were measured in the sheep trachea in vivo. The tracheal arteries were isolated and perfused. An isolated segment of tracheal lumen was filled with Krebs-Henseleit solution containing 99mTc-DTPA, and radioactivity was measured in blood from a catheterized tracheal vein. Infusions at constant pressure of methacholine (n = 5), albuterol (n = 6), and histamine (n = 5) increased arterial inflow [+250 +/- 73.0, +74.2 +/- 22.9, +68.9 +/- 39.2% (SE), respectively] and venous outflow (+49.5 +/- 13.8, +11.6 +/- 4.5, +6.2 +/- 13.9%) but decreased 99mTc-DTPA output (-36.8 +/- 8.4, -20.4 +/- 6.2, -58.1 +/- 11.7%) and concentration (-53.9 +/- 10.1, -27.3 +/- 7.5, -49.3 +/- 14.4%). Phenylephrine (n = 9) decreased arterial inflow (-49.4 +/- 10.0%) and venous outflow (-4.1 +/- 5.9%) but increased 99mTc-DTPA output (+74.6 +/- 44.2%) and concentration (+94.4 +/- 56.6%). When the tracheal arteries were initially perfused at constant flow and the flow rate was then changed, 50% increases in flow (n = 5) increased perfusion pressure (+35.9 +/- 2.2%) and venous outflow (+10.5 +/- 3.8%) but decreased 99mTc-DTPA output (-24.4 +/- 7.8%) and concentration (-30.4 +/- 8.8%). Decreases in flow of 50% (n = 3) and 100% (n = 10) decreased perfusion pressure (-34.2 +/- 4.2, -80.1 +/- 3.5%, respectively) and venous outflow (-11.0 +/- 4.8, -29.7 +/- 7.2%) but increased 99mTc-DTPA output (+45.9 +/- 27.5, +167.4 +/- 70.4%) and concentration (+64.7 +/- 26.7, +305.7 +/- 110.2%).(ABSTRACT TRUNCATED AT 250 WORDS)     

Morphologic adaptation of arterial endothelial cells to longitudinal stretch in organ culture

Arteries in vivo are subjected to large longitudinal stretch, which changes significantly due to vascular disease and surgery. However, little is known about the effect of longitudinal stretch on arterial endothelium. The aim of this study was to determine the morphologic adaptation of arterial endothelial cells (ECs) to elevated axial stretch. Porcine carotid arteries were stretched 20% more than their in vivo length while being maintained at physiological pressure and flow rate in an organ culture system. The ECs were elongated with the application of the axial stretch (aspect ratio 2.81+/-0.25 versus 3.65+/-0.38, n=8, p<0.001). The elongation was slightly decreased after three days and the ECs recovered their normal shape after seven days, as measured by the shape index and aspect ratio (0.55+/-0.03 versus 0.56+/-0.04, and 2.93+/-0.28 versus 2.88+/-0.20, respectively, n=5). Cell proliferation was increased in the intima of stretched arteries in three days as compared to control arteries but showed no difference after seven days in organ culture. These results demonstrate that the ECs adapt to axial stretch and maintain their normal shape.     

Flow-induced control of arterial lumen

Blood flow velocity is a factor that affects the diameter of arteries. In order to investigate the flow-induced arterial dilatation, the outer diameter of the femoral, common carotid or renal arteries of anaesthetized cats was measured during perfusion of these arteries with blood or plasma-substituting solutions under conditions of stabilized perfusion pressure. It has been shown that, whatever the perfusate, blood or a substituent, an increase in flow makes the artery to dilate. Consequently, the flow-induced dilatation is not due to any blood-borne humoral factor. As an increase in the solution's viscosity causes dilatation even at constant flow-rate and pressure in the artery, the effect is to be ascribed to the ability of the vascular wall to perceive shear stress. As far as removal of endothelium eliminates the dilatation evoked by increasing flow or fluid viscosity, it may be concluded that the flow-induced dilatation is due to the sensitivity to shear stress of the endothelium.     

Exercise reduces arterial pressure augmentation through vasodilation of muscular arteries in humans

Exercise markedly influences pulse wave morphology, but the mechanism is unknown. We investigated whether effects of exercise on the arterial pulse result from alterations in stroke volume or pulse wave velocity (PWV)/large artery stiffness or reduction of pressure wave reflection. Healthy subjects (n = 25) performed bicycle ergometry. with workload increasing from 25 to 150 W for 12 min. Digital arterial pressure waveforms were recorded using a servo-controlled finger cuff. Radial arterial pressure waveforms and carotid-femoral PWV were determined by applanation tonometry. Stroke volume was measured by echocardiography, and brachial and femoral artery blood flows and diameters were measured by ultrasound. Digital waveforms were recorded continuously. Other measurements were made before and after exercise. Exercise markedly reduced late systolic and diastolic augmentation of the peripheral pressure pulse. At 15 min into recovery, stroke volume and PWV were similar to baseline values, but changes in pulse wave morphology persisted. Late systolic augmentation index (radial pulse) was reduced from 54 +/- 3.9% at baseline to 42 +/- 3.7% (P < 0.01), and diastolic augmentation index (radial pulse) was reduced from 37 +/- 1.8% to 25 +/- 2.9% (P < 0.001). These changes were accompanied by an increase in femoral blood flow (from 409 +/- 44 to 773 +/- 48 ml/min, P < 0.05) and an increase in femoral artery diameter (from 8.2 +/- 0.4 to 8.6 +/- 0.4 mm, P < 0.05). In conclusion, exercise dilates muscular arteries and reduces arterial pressure augmentation, an effect that will enhance ventricular-vascular coupling and reduce load on the left ventricle.     

Tracheal vascular and smooth muscle responses to air temperature and humidity in dogs

Twenty-five dogs were anesthetized, paralyzed, and artificially ventilated. Their cranial tracheal arteries were perfused bilaterally with blood at constant flow, and the perfusion pressures (Patr) were measured. Tracheal smooth muscle function was assessed by recording changes in external diameter (delta Dtr). The perfused segment of the trachea was exposed to air at a constant unidirectional airflow of 25 l/min. Group 1 (n = 6) was exposed to cold dry air, ambient room air, and hot dry and hot humid air, each for 10 min with exposures starting from zero flow. The tracheal vascular responses to all four conditions were small vasodilations (delta Patr from -2 to -6%) followed by recovery or small vasoconstrictions. In group 2 (n = 19), exposures to cold dry and hot humid air were preceded and followed by body-temperature fully humidified air. Cold dry air caused a sustained vasodilation (delta Patr -9.0 +/- 1.1%), and hot humid air usually caused a biphasic response: a vasoconstriction (delta Patr 4.4 +/- 1.0%) followed by a vasodilation (delta Patr -5.7 +/- 1.9%). The warm humid air after cold dry air or hot humid air caused a further vasodilation, which lasted a short time after cold dry air (delta Patr -3.7 +/- 0.4%) but greater than 10 min after hot humid air (delta Patr -13.8 +/- 1.4%). In both groups, all exposures that cooled the trachea (cold dry air, ambient room air, and hot dry air) caused smooth muscle contraction, and hot humid air that warmed the trachea caused relaxation.     

Effect of in vivo fetal infusion of dexamethasone at 0.75 GA on fetal ovine resistance artery responses to ET-1

At 110-111 days gestation, instrumented fetal sheep were administered saline or dexamethasone (2.2 microgram. kg(-1). h(-1) iv) for 48 h. Measurement of fetal blood pressure showed a greater increase in dexamethasone-treated (n = 6) compared with control (n = 5) fetuses (7.3 +/- 2.3 vs. 0.6 +/- 2.3 mmHg, P < 0.05). Fetuses were delivered by cesarean section, and the femoral muscle and brain were obtained under halothane anesthesia. Femoral and middle cerebral arteries (approximately 320-micrometer internal diameter) were evaluated using wire myography. Sensitivity to KCl (2.5-125 mM) and the magnitude of the maximal vasoconstriction to 125 mM K(+) were similar in femoral and middle cerebral arteries from dexamethasone-treated vs. control fetuses. Acetylcholine-induced vasorelaxation was similar in femoral arteries from control and dexamethasone-treated fetuses. Middle cerebral arteries did not relax to acetylcholine. Sensitivity to endothelin-1 (ET-1; 0.1 pM-0.1 microM) and magnitude of the ET-1-induced vasoconstriction were greater in femoral arteries from dexamethasone-treated vs. control fetuses (P < 0.05). Autoradiographical studies with receptor-specific ligands demonstrated increased ET(A)-receptor binding, the principal receptor subtype, in femoral muscle vessels (P < 0.001) but decreased ET(A)-receptor binding in middle cerebral arteries (P < 0.01) from dexamethasone-treated compared with control fetuses. Relatively little ET(B)-receptor binding was evident in all tissues examined. We conclude that hyperreactivity to ET-1, due to increased ET(A)-receptor binding, may be involved in the dexamethasone-induced increase in peripheral vascular resistance in fetal sheep in vivo.     

Myogenic response of rat femoral small arteries in relation to wall structure and [Ca(2+)](i)

The present study investigated the influence of media thickness on myogenic tone and intracellular calcium concentration ([Ca(2+)](i)) in rat skeletal muscle small arteries. A ligature was loosely tied around one external iliac artery of 5-wk-old spontaneously hypertensive rats. At 18 wk of age, femoral artery blood pressure was 102 +/- 11 mmHg (n = 15) on the ligated side and 164 +/- 6 mmHg (n = 15) on the contralateral side. Small arteries feeding the gracilis muscle had a reduced media cross-sectional area and a reduced media-to-lumen ratio on the ligated side, where also the range of myogenic constriction was shifted to lower pressures. However, when expressed as a function of wall stress, diameter responses were nearly identical. [Ca(2+)](i) was higher in vessels from the ligated hindlimb at pressures above 10 mmHg, but vasoconstriction was not accompanied by changes in [Ca(2+)](i). Thus the myogenic constriction here seems due primarily to changes in intracellular calcium sensitivity, which are determined mainly by the force per cross-sectional area of the wall and therefore altered by changes in vascular structure.     

Increased immunohistochemical expression of thrombomodulin at placental perivascular myofibroblast in severe preeclampsia (PE)

The presence of pro-coagulant and anti-coagulant components of the placental vascular endothelium and syncytiotrophoblast are essential for homeostasis. Vascular endothelium prevents blood clot formation in vivo by involving a cell surface thrombin-binding glycoprotein, thrombomodulin (TM), that activates plasma anti-coagulant protein C. The TM levels increase during pregnancy, but the fibrinolytic capacity diminishes. Since vascular lesions with placental coagulation disorders can be associated with preeclampsia (PE), we hypothesized that TM expression in the stem villous vasculature and syncytiotrophoblast of the placenta are impaired in PE. Plasma and placental tissue samples were collected from PE (n=12) and normotensive pregnant patients (n=11). Patient's gestational age was 35.7+/-1.2 (normotensive) and 30.6+/-1.5 weeks (PE). Blood samples were drawn 30 min before delivery. Serum PAI-1 and PAI-2 antigens were determined by enzyme-linked immunoabsorbent assay (ELISA). A monoclonal antibody specific for TM was used for immunohistochemical tissue staining (ABC) and the staining was quantified by semi quantitative scores. Results show no intensity differences at the apical syncytiotrophoblast between the two groups. However, in preeclamptic placenta, TM expression diminished in the endothelium of the stem villi arteries and increased in the perivascular and stromal myofibroblats in cases of severe PE. TM changes were associated with an increased PAI-1/PAI-2 ratio. It is suggested that in severe PE, the decreased placental blood flow may be due to structural and functional impairment of the endothelium of the stem villi vessels and the surrounding perivascular and stromal myofibroblast, by increasing TM expression which may modulate fetal blow flow in the villous tree.     

Cerebral artery responses to pressure and flow in uremic hypertensive and spontaneously hypertensive rats

Impaired cerebral blood flow autoregulation is seen in uremic hypertension, whereas in nonuremic hypertension autoregulation is shifted toward higher perfusion pressure. The cerebral artery constricts in response to a rise in either lumen pressure or flow; we examined these responses in isolated middle cerebral artery segments from uremic Wistar-Kyoto rats (WKYU), normotensive control rats (WKYC), and spontaneously hypertensive rats (SHR). Pressure-induced (myogenic) constriction developed at 100 mmHg; lumen flow was then increased in steps from 0 to 98 microl/min. Some vessels were studied after endothelium ablation. Myogenic constriction was significantly lower in WKYU (28 +/- 2.9%) compared with both WKYC (39 +/- 2.5%, P = 0.035) and SHR (40 +/- 3.1%, P = 0.018). Flow caused constriction of arteries from all groups in an endothelium-independent manner. The response to flow was similar in WKYU and WKYC, whereas SHR displayed increased constriction compared with WKYU (P < 0.001) and WKYC (P < 0.001). We conclude that cerebral myogenic constriction is decreased in WKYU, whereas flow-induced constriction is enhanced in SHR.     

Vascular adaptation to deconditioning and the effect of an exercise countermeasure: results of the Berlin Bed Rest study.

Deconditioning is a risk factor for cardiovascular disease. The physiology of vascular adaptation to deconditioning has not been elucidated. The purpose of the present study was to assess the effects of bed rest deconditioning on vascular dimension and function of leg conduit arteries. In addition, the effectiveness of resistive vibration exercise as a countermeasure for vascular deconditioning during bed rest was evaluated. Sixteen healthy men were randomly assigned to bed rest (BR-Ctrl) or to bed rest with resistive vibration exercise (BR-RVE). Before and after 25 and 52 days of strict horizontal bed rest, arterial diameter, blood flow, flow-mediated dilatation (FMD), and nitroglycerin-mediated dilatation were measured by echo Doppler ultrasound. In the BR-Ctrl group, the diameter of the common femoral artery decreased by 13 +/- 3% after 25 and 17 +/- 1% after 52 days of bed rest (P < 0.001). In the BR-RVE group this decrease in diameter was significantly attenuated (5 +/- 2% after 25 days and 6 +/- 2% after 52 days, P < 0.01 vs. BR-Ctrl). Baseline blood flow did not change after bed rest in either group. After 52 days of bed rest, FMD and nitroglycerin-mediated dilatation of the superficial femoral artery were increased in both groups, possibly by increased nitric oxide sensitivity. In conclusion, bed rest deconditioning is accompanied by a reduction in the diameter of the conduit arteries and by an increased reactivity to nitric oxide. Resistive vibration exercise effectively attenuates the diameter decrease of leg conduit arteries after bed rest.     

Measurements of mouse pulmonary artery biomechanics

BACKGROUND: Robust techniques for characterizing the biomechanical properties of mouse pulmonary arteries will permit exciting gene-level hypotheses regarding pulmonary vascular disease to be tested in genetically engineered animals. In this paper, we present the first measurements of the biomechanical properties of mouse pulmonary arteries. METHOD OF APPROACH: In an isolated vessel perfusion system, transmural pressure, internal diameter and wall thickness were measured during inflation and deflation of mouse pulmonary arteries over low (5-40 mmHg) and high (10-120 mmHg) pressure ranges representing physiological pressures in the pulmonary and systemic circulations, respectively. RESULTS: During inflation, circumferential stress versus strain showed the nonlinear "J"-shape typical of arteries. Hudetz's incremental elastic modulus ranged from 27 +/- 13 kPa (n = 7) during low-pressure inflation to 2,700 +/- 1,700 kPa (n = 9) during high-pressure inflation. The low and high-pressure testing protocols yielded quantitatively indistinguishable stress-strain and modulus-strain results. Histology performed to assess the state of the tissue after mechanical testing showed intact medial and adventitial architecture with some loss of endothelium, suggesting that smooth muscle cell contractile strength could also be measured with these techniques. CONCLUSIONS: The measurement techniques described demonstrate the feasibility of quantifying mouse pulmonary artery biomechanical properties. Stress-strain behavior and incremental modulus values are presented for normal, healthy arteries over a wide pressure range. These techniques will be useful for investigations into biomechanical abnormalities in pulmonary vascular disease.     

ATP-mediated release of arachidonic acid metabolites from venular endothelium causes arteriolar dilation

This study was designed to test the hypothesis that venular administration of ATP resulted in endothelium-dependent dilation of adjacent arterioles through a mechanism involving cyclooxygenase products. Forty-three male golden hamsters were anesthetized with pentobarbital sodium (60 mg/kg ip), and the cremaster muscle was prepared for in vivo microscopy. ATP (100 microM) injected into venules dilated adjacent arterioles from a mean diameter of 51 +/- 4 to 76 +/- 6 microm (P < 0.05, n = 6). To remove the source of endothelial-derived relaxing factors, the venules were then perfused with air bubbles to disrupt the endothelium. Resting arteriolar diameter was not altered after disruption of the venular endothelium (51 +/- 5 microm), and the responses to venular ATP infusions were significantly attenuated (59 +/- 4 microm, P < 0.05). To determine whether the relaxing factor was a cyclooxygenase product, ATP infusion studies were repeated in the absence and presence of indomethacin (28 microM). Under control conditions, ATP (100 microM) infusion into the venule caused an increase in mean arteriolar diameter from 55 +/- 4 to 78 +/- 3 microm (P < 0.05, n = 6). In the presence of indomethacin, mean resting arteriolar tone was not significantly altered (49 +/- 4 microm), and the response to ATP was significantly attenuated (54 +/- 4 microm, P < 0.05, n = 6). These studies show that increases in venular ATP concentrations stimulate the release of cyclooxygenase products, possibly from the venular endothelium, to vasodilate the adjacent arteriole.     

Resveratrol reduction of infarct size in Long-Evans rats subjected to focal cerebral ischemia

Although vasomotion has been considered a feature of the microvascular bed under physiological conditions, it has also been observed following hypotension in several tissues. In this work, 158 mesenteric microvessels of 36 rats were investigated quantitatively in normovolemic and hemorrhaged animals, focussing on diameter changes, particularly vasomotion incidence and characteristics. The femoral arteries of Wistar rats (body weight BW = 188 +/- 23 g, mean +/- SD) anesthetized with pentobarbital were cannulated for arterial pressure (AP) monitoring and blood withdrawal. The protocol consisted of 15 min control and 30 min of hemorrhagic hypotension (AP = 52 +/- 5 mmHg, hemorrhaged vol. = 17 +/- 4 ml/kg BW). During control normovolemic conditions, analysis of mesenteric microcirculation using intravital videomicroscopy revealed neither arteriolar nor venular vasomotion. During hemorrhagic hypotension (HH) microvascular blood flow reduced to 25% of control. While venules did not show diameter changes during HH, arterioles contracted to 85 +/- 20% of control and arteriolar vasomotion appeared in 42% of the animals and 27% of the arterioles. The amplitude of arteriolar diameter change during HH relative to mean diameter and to control diameter averaged 65 +/- 24% (range: 32-129%) and 41 +/- 10% (range: 25-62%), respectively. Vasomotion analysis showed two major frequency components: 1.7 +/- 0.8 and 7.0 +/- 5.2 cycles/min. Arterioles showing vasomotion had a mean control diameter larger than the remaining arterioles and showed the largest constriction during HH. We conclude that hemorrhagic hypotension does not change venular diameter but induces arteriolar constriction and vasomotion in rat mesentery. This activity is expressed as slow waves with high amplitude and fast waves with low amplitude, and is dependent on vessel size.     

Endothelium-dependent and -independent vasodilation of the superficial femoral artery in spinal cord-injured subjects

Extreme inactivity of the legs in spinal cord-injured (SCI) individuals does not result in an impairment of the superficial femoral artery flow-mediated dilation (FMD). To gain insight into the underlying mechanism, the present study examined nitric oxide (NO) responsiveness of vascular smooth muscles in controls and SCI subjects. In eight healthy men (34 +/- 13 yr) and six SCI subjects (37 +/- 10 yr), superficial femoral artery FMD response was assessed by echo Doppler. Subsequently, infusion of incremental dosages of sodium nitroprusside (SNP) was used to assess NO responsiveness. Peak diameter was examined on a second day after 13 min of arterial occlusion in combination with sublingual administration of nitroglycerine. Resting and peak superficial femoral artery diameter in SCI subjects were smaller than in controls (P < 0.001). The FMD response in controls (4.2 +/- 0.9%) was lower than in SCI subjects (8.2 +/- 0.9%, P < 0.001), but not after correcting for area under the curve for shear rate (P = 0.35). When expressed as relative change from baseline, SCI subjects demonstrate a significantly larger diameter increase compared with controls at each dose of SNP. However, when expressed as a relative increase within the range of diameter changes [baseline (0%) - peak diameter (100%)], both groups demonstrate similar changes in response to SNP. Changes in diameter during SNP infusion and FMD response are larger in SCI subjects compared with controls. When these results are corrected, superficial femoral artery FMD and NO sensitivity in SCI subjects are not different from those in controls. This illustrates the importance of appropriate data presentation and suggests that, subsequent to structural inward remodeling of conduit arteries as a consequence of extreme physical inactivity, arterial function is normalized.     

Human femoral artery diameter in relation to knee extensor muscle mass, peak blood flow, and oxygen uptake

It is not known whether the diameter of peripheral conduit arteries may impose a limitation on muscle blood flow and oxygen uptake at peak effort in humans, and it is not clear whether these arteries are dimensioned in relation to the tissue volume they supply or, rather, to the type and intensity of muscular activity. In this study, eight humans, with a peak pulmonary oxygen uptake of 3.90 +/- 0.31 (range 2.29-5.03) l/min during ergometer cycle exercise, performed one-legged dynamic knee extensor exercise up to peak effort at 68 +/- 7 W (range 55-100 W). Peak values for knee extensor blood flow (thermodilution) and oxygen uptake of 6.06 +/- 0.74 (range 4.75-9.52) l/min and 874 +/- 124 (range 590-1,521) ml/min, respectively, were achieved. Pulmonary oxygen uptake reached a peak of 1.72 +/- 0.19 (range 1.54-2.33) l/min. Diameters of common and profunda femoral arteries determined by ultrasound Doppler were 10.6 +/- 0.4 (range 8.2-12.7) and 6.0 +/- 0.4 (range 4.5-8.0) mm, respectively. Thigh and quadriceps muscle volume measured by computer tomography were 10.06 +/- 0.66 (range 6.18-10.95) and 2.36 +/- 0.19 (range 1.31-3.27) liters, respectively. The common femoral artery diameter, but not that of the profunda branch, correlated with the thigh volume and quadriceps muscle mass. There were no relationships between either of the diameters and the absolute or muscle mass-related resting and peak values of blood flow and oxygen uptake, peak pulmonary oxygen uptake, or peak power output during knee extensor exercise. However, common femoral artery diameter correlated to peak pulmonary oxygen uptake during ergometer cycle exercise. In conclusion, common and profunda femoral artery diameters are sufficient to ensure delivery to the quadriceps muscle. However, the common branch may impose a limitation during ergometer cycle exercise.     

Conduction of hyperpolarization along hamster feed arteries: augmentation by acetylcholine

The conduction of vasodilation along resistance vessels has been presumed to reflect the electrotonic spread of hyperpolarization from cell to cell along the vessel wall through gap junction channels. However, the vasomotor response to acetylcholine (ACh) encompasses greater distances than can be explained by passive decay. To investigate the underlying mechanism for this behavior, we tested the hypothesis that ACh augments the conduction of hyperpolarization. Feed arteries (n = 23; diameter, 58 +/- 4 microm; segment length, 2-8 mm) were isolated from the hamster retractor muscle, cannulated at each end, and pressurized to 75 mmHg (at 37 degrees C). Vessels were impaled with one or two dye-containing microelectrodes simultaneously (separation distance, 50 microm to 3.5 mm). Membrane potential (E(m)) (rest, approximately -30 mV) and electrical responses were similar between endothelium and smooth muscle, as predicted for robust myoendothelial coupling. Current injection (-0.8 nA, 1.5 s) evoked hyperpolarization (-10 +/- 1 mV; membrane time constant, 240 ms) that conducted along the vessel with a length constant (lambda) = 1.2 +/- 0.1 mm; spontaneous E(m) oscillations (approximately 1 Hz) decayed with lambda = 1.2 + 0.1 mm. In contrast, ACh microiontophoresis (500 nA, 500 ms, 1 microm tip) evoked hyperpolarization (-14 +/- 2 mV) that conducted with lambda = 1.9 +/- 0.1 mm, 60% further (P < 0.05) than responses evoked by purely electrical stimuli. These findings indicate that ACh augments the conduction of hyperpolarization along the vessel wall.     

Transport of uterine PGF2 alpha to the ovaries by systemic circulation and local lymphovenous-arterial diffusion during luteolysis in sheep.

The theory of countercurrent vascular transfer of PGF2 alpha during luteolysis was examined. In the first experiment, pulmonary clearance of PGF2 alpha was determined to re-examine whether the total amount of PGF2 alpha was degraded in the lungs after one passage. Cardiac output was measured by the Fick method and PGF2 alpha by radio-immunoassay before and after vascular lung supply, using pulmonary catheterization and the interventional radiology method in ten anaesthetized ewes on day 16 of the oestrous cycle. Cardiac output remained stable (7156 +/- 439 ml min-1). Infusion of 5 iu oxytocin resulted in an increase in plasma PGF2 alpha concentrations at 30 min in the uterine vein and the pulmonary and femoral arteries (3811 +/- 806, 224 +/- 55 and 18 +/- 4 pg ml-1, respectively). The PGF2 alpha concentrations decreased exponentially and the half-time decreases were 27 (r = 0.99), 16 (r = 0.99) and 18 (r = 0.98) min, respectively. Pulmonary clearance of PGF2 alpha was estimated at 6338 +/- 451 ml min-1. In a second experiment, an arterio-arterial gradient of plasma PGF2 alpha concentrations was analysed between the proximal and distal segments of the ovarian artery to verify whether the total amount of PGF2 alpha flowing to the ovary was from the local venous-arterial countercurrent pathway. Surgical catheterization techniques were performed on 11 ewes on day 16 of the oestrous cycle. The ovarian arterial blood flow was measured by the implantable Doppler method (8 +/- 1 ml min-1). The maximum plasma PGF2 alpha concentrations in the femoral and distal ovarian arteries were 23 +/- 6 and 42 +/- 11 pg ml-1 (P < 0.05), respectively. Plasma PGF2 alpha decreased exponentially in the femoral artery and the half-time decrease was 26 min (r = 0.98), and in the distal ovarian artery close to the ovary PGF2 alpha decreased linearly and the half-time decrease was 108 min (r = 0.96). Consequently, the arterio-arterial diffusion gradient of PGF2 alpha concentrations was extended to 3 h. These experiments showed that the PGF2 alpha flow rate in the pulmonary artery was 42.275 +/- 10.793 micrograms per 150 min (n = 10) and the systemic arterial PGF2 alpha flow rate was 5.359 +/- 1.658 micrograms per 150 min (n = 10). Therefore, 12% of the PGF2 alpha was not oxidized by the lungs. The proximal ovarian PGF2 alpha flow rate was 6.909 +/- 2.341 ng per 150 min, while the distal flow rate was 21.003 +/- 5.703 ng per 150 min (n = 11). Thus, 33% of the PGF2 alpha was transported rapidly to the ovary via the systemic route, while 67% was transported by slow local countercurrent diffusion, which extended the duration of luteolytic activity to four times that of the PGF2 alpha surge. These results indicate both rapid systemic transport of PGF2 alpha to the ovaries and a slower buffer mechanism involving a local diffusion pathway, rather than a direct countercurrent system.