Instillation of bradykinin into femoral artery elicits cardiorespiratory reflexes involving perivascular afferents in anesthetized rats.

The physiology of baroreceptors and chemoreceptors present in large blood vessels of the heart is well known in the regulation of cardiorespiratory functions. Since large blood vessels and peripheral blood vessels are of the same mesodermal origin, therefore, involvement of the latter in the regulation of cardiorespiratory system is expected. The role of perivascular nerves in mediating cardiorespiratory alterations produced after intra-arterial injection of a nociceptive agent (bradykinin) was examined in urethane-anesthetized male rats. Respiratory frequency, blood pressure, and heart rate were recorded for 30 min after the retrograde injection of bradykinin/saline into the femoral artery. In addition, paw edema was determined and water content was expressed as percentage of wet weight. Injection of bradykinin produced immediate tachypneic, hypotensive and bradycardiac responses of shorter latency (5-8 s) favoring the neural mechanisms involved in it. Injection of equi-volume of saline did not produce any responses and served as time-matched control. Paw edema was observed in the ipsilateral hind limb. Pretreatment with diclofenac sodium significantly attenuated the bradykinin-induced responses and also blocked the paw edema. Ipsilateral femoral and sciatic nerve sectioning attenuated bradykinin-induced responses significantly, indicating the origin of responses from the local vascular bed. Administration of bradykinin in the segment of an artery produced reflex cardiorespiratory changes by stimulating the perivascular nociceptors involving prostaglandins. This is a novel study exhibiting the role of peripheral blood vessels in the regulation of the cardiorespiratory system.

Age and sex differences in sympathetic and hemodynamic responses to hypoxia and cold pressor test.

Emerging evidence suggests that sympathetic vasoconstriction is lower in young women. We hypothesized that increases in muscle sympathetic nerve activity (MSNA) during acute physiological stressors induce less vasoconstriction in young women compared to young men. Healthy young men (n = 10, 27 ± 1 years), young women (n = 12, 25 ± 1 years), and older women (n = 10, 63 ± 6 years) performed the cold pressor test (hand in ice for 2 min) and continuous hypoxia (10% O2 , 90% N2 ) for 5 min. MSNA, femoral blood flow velocity, heart rate, and blood pressure were acquired continuously. Femoral artery diameter was obtained every minute and used to calculate femoral blood flow, and femoral vascular resistance and conductance. MSNA responses to cold pressor test (P = 0.345) and hypoxia (P = 0.969) were not different between groups. Young women had greater femoral blood flow (P = 0.002) and vascular conductance (P = 0.041) responses to cold pressor test compared with young men. The femoral blood flow response to hypoxia was not different between the two sexes but the increase in femoral flow was attenuated in older women compared with younger women (P = 0.036). These data show that young women had paradoxical vasodilation to cold pressor test. The mechanisms responsible for the attenuated sympathetic vasoconstriction or for enhanced vasodilation in young women during the CPT require further investigation.

Risk factors to predict leg ischemia in patients undergoing single femoral artery cannulation in minimally invasive cardiac surgery.

BACKGROUND: In peripheral cannulation for cardiopulmonary bypass, there is always a risk of ischemia in the extremities, caused by femoral artery cannulation. This report aimed to evaluate the outcome and the risk factors in patients undergoing minimally invasive cardiac surgery in mitral valve surgery. METHODS: We retrospectively reviewed all minimally invasive mitral valve surgery at our institute from May 2014 to December 2016. Operative outcomes and intra-operative monitoring for distal leg saturation were measured by the near-infrared spectroscopy values. For post-operative outcomes, the creatinine phosphorus kinase level was measured for the assessment of leg ischemia. Risk factors were evaluated for the elevation of post-operative creatinine phosphorus kinase. RESULTS: There were 162 patients who underwent single femoral artery cannulation for minimally invasive mitral valve surgery. The mean operation, cardiopulmonary bypass and aortic cross-clamp time were 212±44, 124±30, 76.6±22 minutes (min), respectively. The factors related to increased creatinine phosphorus kinase were male, body mass index, larger cannula size, operation time, cardiopulmonary bypass time and aortic cross-clamp time. The measurement of minimum near-infrared spectroscopy values did not show any association with creatinine phosphorus kinase elevation. There were significant associations between body mass index, cannula size and operation time and post-operative creatinine phosphorus kinase increase by multiple regression analysis. Two male patients had extremely high post-operative creatinine phosphorus kinase (18188 U/L and 16831 U/L) and they had high body mass index, large cannula size and longer operation time. CONCLUSIONS: In peripheral cannulation for minimally invasive cardiac surgery, body mass index, cannula size and operation time can be considered as risk factors for leg ischemia.

Denervation in Femoral Artery-Ligated Hindlimbs Diminishes Ischemic Recovery Primarily via Impaired Arteriogenesis.

AIMS: Multiple factors regulate arteriogenesis. Peripheral nerves play a crucial role in vascular remodeling, but the function of peripheral nerves during arteriogenesis is obscure. Our study investigated the contribution of denervation to arteriogenesis during post-ischemic recovery from hindlimb femoral artery ligation. METHODS AND RESULTS: Sprague-Dawley rats were randomly allocated into four groups of normal control (NC), hindlimb ischemia (HI), hindlimb ischemia with denervation (HID) and hindlimb simple denervation (HD). Hindlimb ischemic recovery was assessed by clinical assessment and tibialis anterior muscle remodeling on day 28 post-surgery. Blood flow was determined by laser Doppler imaging on day 0, 3, 7, 14 and 28 post-surgery. Collateral number of hindlimb was observed by angiography and gracilis muscles were tested by immunostaining on day 7 and 28 post-surgery. Angiogenesis was accessed by counting CD31 positive capillaries in tibialis anterior muscles on day 28 post-surgery. Group HID showed impaired ischemic recovery compared with the other 3 groups and impaired blood flow recovery compared with group HI on day 28 post-surgery. The collateral number and capillary density of group HID were lower than group HI. The collateral diameter of both group HID and group HI significantly increased compared with group NC. However, the lumen diameter was much narrower and the vessel wall was much thicker in group HID than group HI. We also demonstrated that the thickened neointima of collaterals in group HID comprised of smooth muscle cells and endothelial cells. CONCLUSIONS: Denervation of the ligated femoral artery in the hindlimb impairs ischemic recovery via impaired perfusion. The possible mechanisms of impaired perfusion are lower collateral number, lower capillary density and most likely narrower lumen, which damage ischemic recovery. This study illustrates the crucial role of peripheral nerves in arteriogenesis using a model combined ischemia with denervation in hindlimb.

Label-free in vivo imaging of peripheral nerve by multispectral photoacoustic tomography.

Unintentional surgical damage to nerves is mainly due to poor visualization of nerve tissue relative to adjacent structures. Multispectral photoacoustic tomography can provide chemical information with specificity and ultrasonic spatial resolution with centimeter imaging depth, making it a potential tool for noninvasive neural imaging. To implement this label-free imaging approach, a multispectral photoacoustic tomography platform was built. Imaging depth and spatial resolution were characterized. In vivo imaging of the femoral nerve that is 2 mm deep in a nude mouse was performed. Through multivariate curve resolution analysis, the femoral nerve was discriminated from the femoral artery and chemical maps of their spatial distributions were generated.

Impact of shear rate pattern on upper and lower limb conduit artery endothelial function in both spinal cord-injured and able-bodied men.

NEW FINDINGS: What is the central question of this study? This study addresses the following two central questions. (i) What is the impact of vascular deconditioning after spinal cord injury (SCI) on shear rate patterns and endothelial function? (ii) What is the impact of acutely altered shear rate on endothelial function in both SCI and able-bodied control subjects? What is the main finding and its importance? Two main findings in the present study were as follows: (i) reduced superficial femoral artery endothelial function in the SCI group; and (ii) acutely altered shear rate decreased endothelial function in both SCI and able-bodied control subjects. These findings may shed some light on future interventions taking into account these regulatory mechanisms. Spinal cord injury (SCI) induces vascular deconditioning below the level of the lesion and disrupts sympathetic innervation of blood vessels. It is unclear how these changes affect shear rate (SR) profiles and endothelial function when compared with able-bodied (AB) persons. Recent evidence suggests that periods of increased retrograde SR are associated with acute decreases in endothelial function, but is unknown how modified SR patterns influence sublesional vasculature in SCI. The present study examined the acute and chronic effects of altered SR patterns and oscillatory shear index on endothelial function via relative flow-mediated dilatation (FMD%) in both the brachial and superficial femoral arteries (BA and SFA, respectively) of eight individuals with SCI and eight matched AB control subjects. Baseline BA SR patterns and FMD% were similar between groups, while SFA anterograde SR was higher (P < 0.01) and FMD% lower (P = 0.04) in SCI versus AB subjects. Shear rate patterns were then acutely altered through the BA and SFA using a subsystolic cuff-inflation model. Bilateral FMD assessments were conducted before and after 30 min of unilateral inflation of a forearm or thigh blood pressure cuff to 75 mmHg. Cuff inflation resulted in concomitant increases in both anterograde (P < 0.05) and retrograde SR (P < 0.05), as well as acute decreases in FMD% (P < 0.05) in the BA and SFA in both groups. These results highlight that brief manipulation of SR patterns can acutely impair FMD% in conditions of both normal and altered sympathetic innervation and arterial remodelling. This information is crucial when designing strategies to combat impaired vascular function in both healthy and clinical populations.

Local sympathetic denervation of femoral artery in a rabbit model by using 6-hydroxydopamine in situ.

Both artery bundle and sympathetic nerve were involved with the metabolism of bone tissues. Whether the enhancing effects of artery bundle result from its accompanying sympathetic nerve or blood supply is still unknown. There is no ideal sympathetic nerve-inhibited method for the in situ denervation of artery bundle. Therefore, we dipped the femoral artery in the 6-hydroxydopamine (6-OHDA) locally and observed its effect. Compared with control group, the in situ treatment of 6-OHDA did not damage the normal structure of vascular bundle indicated by hematoxylin-eosin (HE) staining. However, the functions of sympathetic nerve was completely inhibited for more than 2 weeks, and only a few function of sympathetic nerve resumed 4 weeks later, evidenced by glyoxylic acid staining and the expression of tyrosine hydroxylase (TH) and nerve peptide Y (NPY). Thus, 6-OHDA is promising as an ideal reagent for the local denervation of sympathetic nerve from artery system.

Exercise training improves functional sympatholysis in spontaneously hypertensive rats through a nitric oxide-dependent mechanism.

Functional sympatholysis is impaired in hypertensive animals and patients. Exercise training (ET) improves functional sympatholysis through a nitric oxide (NO)-dependent mechanism in normotensive rats. However, whether ET has similar physiological benefits in hypertension remains to be elucidated. Thus we tested the hypothesis that the impairment in functional sympatholysis in hypertension is reversed by ET through a NO-dependent mechanism. In untrained normotensive Wistar-Kyoto rats (WKYUT; n = 13), untrained spontaneously hypertensive rats (SHRUT; n = 13), and exercise-trained SHR (SHRET; n = 6), changes in femoral vascular conductance (FVC) were examined during lumbar sympathetic nerve stimulation (1, 2.5, and 5 Hz) at rest and during muscle contraction. The magnitude of functional sympatholysis (Δ%FVC = Δ%FVC muscle contraction - Δ%FVC rest) in SHRUT was significantly lower than WKYUT (1 Hz: -2 ± 4 vs. 13 ± 3%; 2.5 Hz: 9 ± 3 vs. 21 ± 3%; and 5 Hz: 12 ± 3 vs. 26 ± 3%, respectively; P < 0.05). Three months of voluntary wheel running significantly increased maximal oxygen uptake in SHRET compared with nontrained SHRUT (78 ± 6 vs. 62 ± 4 ml·kg(-1)·min(-1), respectively; P < 0.05) and restored the magnitude of functional sympatholysis in SHRET (1 Hz: 9 ± 2%; 2.5 Hz: 20 ± 4%; and 5 Hz: 34 ± 5%). Blockade of NO synthase (NOS) by N(G)-nitro-l-arginine methyl ester attenuated functional sympatholysis in WKYUT but not SHRUT. Furthermore, NOS inhibition significantly diminished the improvements in functional sympatholysis in SHRET. These data demonstrate that impairments in functional sympatholysis are normalized via a NO mechanism by voluntary wheel running in hypertensive rats.

Intravital Förster resonance energy transfer imaging reveals elevated [Ca2+]i and enhanced sympathetic tone in femoral arteries of angiotensin II-infused hypertensive biosensor mice.

Artery narrowing in hypertension can only result from structural remodelling of the artery, or increased smooth muscle contraction. The latter may occur with, or without, increases in [Ca(2+)]i. Here, we sought to measure, in living hypertensive mice, possible changes in artery dimensions and/or [Ca(2+)]i, and to determine some of the mechanisms involved. Ca(2+)/calmodulin biosensor (Förster resonance energy transfer-based) mice were made hypertensive by s.c. infusion of angiotensin II (Ang II, 400 ng kg(-1) min(-1), 2-3 weeks). Intravital fluorescence microscopy was used to determine [Ca(2+)]i and outer diameter of surgically exposed, intact femoral artery (FA) of anaesthetized mice. Active contractile FA 'tone' was calculated from the basal-state diameter and the passive (i.e. Ca(2+)-free) diameter (PD). Compared to saline control, FAs of Ang II-infused mice had (1) ∼21% higher active tone and (2) ∼78 nm higher smooth muscle [Ca(2+)]i, but (3) the same PDs. The local Ang II receptor (AT1R) blocker losartan had negligible effect on tone or [Ca(2+)]i in control FAs, but reduced the basal tone by ∼9% in Ang II FAs. Both i.v. hexamethonium and locally applied prazosin abolished the difference in FA tone and [Ca(2+)]i, suggesting a dominant role of sympathetic nerve activity (SNA). Changes in diameter and [Ca(2+)]i in response to locally applied phenylephrine, Ang II, arginine vasopressin, elevated [K(+)]o and acetylcholine were not altered. In summary, FAs of living Ang II hypertensive mice have higher [Ca(2+)]i, and are more constricted, due, primarily, to elevated SNA and some increased arterial AT1R activation. Evidence of altered artery reactivity or remodeling was not found.

High vascular tone of mouse femoral arteries in vivo is determined by sympathetic nerve activity via α1A- and α1D-adrenoceptor subtypes.

BACKGROUND AND PURPOSE: Determining the role of vascular receptors in vivo is difficult and not readily accomplished by systemic application of antagonists or genetic manipulations. Here we used intravital microscopy to measure the contributions of sympathetic receptors, particularly α1-adrenoceptor subtypes, to contractile activation of femoral artery in vivo. EXPERIMENTAL APPROACH: Diameter and intracellular calcium ([Ca(2+)]i) in femoral arteries were determined by intravital fluorescence microscopy in mice expressing a Myosin Light Chain Kinase (MLCK) based calcium-calmodulin biosensor. Pharmacological agents were applied locally to the femoral artery to determine the contributions of vascular receptors to tonic contraction and [Ca(2+)]i,. KEY RESULTS: In the anesthetized animal, femoral arteries were constricted to a diameter equal to 54% of their passive diameter (i.e. tone = 46%). Of this total basal tone, 16% was blocked by RS79948 (0.1 µM) and thus attributable to α2-adrenoceptors. A further 46% was blocked by prazosin (0.1 µM) and thus attributable to α1-adrenoceptors. Blockade of P2X and NPY1 receptors with suramin (0.5 mM) and BIBP3226 (1.0 µM) respectively, reduced tone by a further 22%, leaving 16% of basal tone unaffected at these concentrations of antagonists. Application of RS100329 (α1A-selective antagonist) and BMY7378 (α1D-selective) decreased tone by 29% and 26%, respectively, and reduced [Ca(2+)]i. Chloroethylclonidine (1 µM preferential for α1B-) had no effect. Abolition of sympathetic nerve activity (hexamethonium, i.p.) reduced basal tone by 90%. CONCLUSION AND IMPLICATIONS: Tone of mouse femoral arteries in vivo is almost entirely sympathetic in origin. Activation of α1A- and α1D-adrenoceptors elevates [Ca(2+)]i and accounts for at least 55% of the tone.

Spontaneous bursts of muscle sympathetic nerve activity decrease leg vascular conductance in resting humans.

Previous studies in humans attempting to assess sympathetic vascular transduction have related large reflex-mediated increases in muscle sympathetic nerve activity (MSNA) to associated changes in limb vascular resistance. However, such procedures do not provide insight into the ability of MSNA to dynamically control vascular tone on a beat-by-beat basis. Thus we examined the influence of spontaneous MSNA bursts on leg vascular conductance (LVC) and how variations in MSNA burst pattern (single vs. multiple bursts) and burst size may affect the magnitude of the LVC response. In 11 young men, arterial blood pressure, common femoral artery blood flow, and MSNA were continuously recorded during 20 min of supine rest. Signal averaging was used to characterize percent changes in LVC for 15 cardiac cycles following heartbeats associated with and without MSNA bursts. LVC significantly decreased following MSNA bursts, reaching a nadir during the 6th cardiac cycle (single bursts, -2.9 ± 1.1%; and multiple bursts, -11.0 ± 1.4%; both, P < 0.001). Individual MSNA burst amplitudes and the total amplitude of consecutive bursts were related to the magnitude of peak decreases in LVC. In contrast, cardiac cycles without MSNA bursts were associated with a significant increase in LVC (+3.1 ± 0.5%; P < 0.001). Total vascular conductance decreased in parallel with LVC also reaching a nadir around the peak rise in arterial blood pressure following an MSNA burst. Collectively, these data are the first to assess beat-by-beat sympathetic vascular transduction in resting humans, demonstrating robust and dynamic decreases in LVC following MSNA bursts, an effect that was absent for cardiac cycles without MSNA bursts.

Blockade of the TP receptor attenuates the exercise pressor reflex in decerebrated rats with chronic femoral artery occlusion.

Cyclooxygenase metabolites stimulate or sensitize group III and IV muscle afferents, which comprise the sensory arm of the exercise pressor reflex. The thromboxane (TP) receptor binds several of these metabolites, whose concentrations in the muscle interstitium are increased by exercise under freely perfused conditions and even more so under ischemic conditions, which occur in peripheral artery disease. We showed that the exercise pressor reflex is greater in rats with simulated peripheral artery disease than in rats with freely perfused limbs. These findings prompted us to test the hypothesis that the TP receptor contributes to the exaggerated exercise pressor reflex occurring in a rat model of peripheral artery disease. We compared the cardiovascular responses to static contraction and stretch before and after femoral arterial injections of daltroban (80 µg), a TP receptor antagonist. We performed these experiments in decerebrate rats whose femoral arteries were ligated 72 h before the experiment (a model of simulated peripheral artery disease) and in control rats whose hindlimbs were freely perfused. Daltroban reduced the pressor response to static contraction in both freely perfused (n = 6; before: Δ12 ± 2 mmHg, after: Δ6 ± 2 mmHg, P = 0.024) and 72-h-ligated rats (n = 10; before: Δ25 ± 3 mmHg, after: Δ7 ± 4 mmHg, P = 0.001). Likewise, daltroban reduced the pressor response to stretch in the freely perfused group (n = 9; before: Δ30 ± 3 mmHg, after: Δ17 ± 3 mmHg, P < 0.0001) and in the ligated group (n = 11; before: Δ37 ± 5 mmHg, after: Δ23 ± 3 mmHg, P = 0.016). Intravenous injections of daltroban had no effect on the pressor response to contraction. We conclude that the TP receptor contributes to the pressor responses evoked by contraction and stretch in both freely perfused rats and rats with simulated peripheral artery disease.

Vascular-dependent effects of elevated glucose on postganglionic sympathetic neurons.

Perivascular sympathetic nerves are important determinants of vascular function that are likely to contribute to vascular complications associated with hyperglycemia and diabetes. The present study tested the hypothesis that glucose modulates perivascular sympathetic nerves by studying the effects of 7 days of hyperglycemia on norepinephrine (NE) synthesis [tyrosine hydroxylase (TH)], release, and uptake. Direct and vascular-dependent effects were studied in vitro in neuronal and neurovascular cultures. Effects were also studied in vivo in rats made hyperglycemic (blood glucose >296 mg/dl) with streptozotocin (50 mg/kg). In neuronal cultures, TH and NE uptake measured in neurons grown in high glucose (HG; 25 mM) were less than that in neurons grown in low glucose (LG; 5 mM) (P < 0.05; n = 4 and 6, respectively). In neurovascular cultures, elevated glucose did not affect TH or NE uptake, but it increased NE release. Release from neurovascular cultures grown in HG (1.8 ± 0.2%; n = 5) was greater than that from cultures grown in LG (0.37 ± 0.28%; n = 5; P < 0.05; unpaired t-test). In vivo, elevated glucose did not affect TH or NE uptake, but it increased NE release. Release in hyperglycemic animals (9.4 + 1.1%; n = 6) was greater than that in control animals (5.39 + 1.1%; n = 6; P < 0.05; unpaired t-test). These data identify a novel vascular-dependent effect of elevated glucose on postganglionic sympathetic neurons that is likely to affect the function of perivascular sympathetic nerves and thereby affect vascular function.

Effects of cold pressor-induced sympathetic stimulation on the mechanical properties of common carotid and femoral arteries in healthy males.

Our aim was to evaluate the effects of sympathetic excitation and elevation of blood pressure on mechanical properties of common carotid and femoral arteries by wave intensity analysis (WIA). The diameters and arterial stiffness parameters of right common carotid artery (RCCA) and right common femoral artery (RCFA) in healthy young men were measured by WIA at baseline and during cold pressor test (CPT). In addition, the blood pressure and heart rate were recorded simultaneously. The heart rates and blood pressures increased during CPT compared with baseline, while the pulse pressures remained unchanged. The diameters of RCCA increased slightly, while those of RCFA did not change. The Peterson's pressure modulus (Ep), augment index (AI), and pulse wave velocity from ß (PWVß) increased obviously, while arterial compliance (AC) decreased with no change in stiffness index (ß) of both arteries during CPT when compared with baseline. There was an obvious increase in pulse wave velocity from wave intensity (PWV_WI) of RCCA, while the PWV_WI of RCFA showed no significant change during CPT. The sympathetic nervous system exerts a more marked tonic restraint on RCFA than on RCCA. The Ep, AC, AI, PWVß of RCCA, and RCFA are much affected by variations in blood pressure and sympathetic status, while the ß of both arteries are less vulnerable to these factors and are more reliable in reflecting the actual arterial stiffness; The PWV_WI appears to be suitable only for evaluating the stiffness of RCCA instead of RCFA.

Eph/ephrin interactions modulate vascular sympathetic innervation.

Ephs and ephrins are membrane-bound proteins that interact to modulate axon growth and neuronal function. We tested the hypothesis that eph/ephrin interactions affected the growth and function of vascular sympathetic innervation. Using RT-PCR analyses, we detected both classes of ephs (A and B) and both classes of ephrins (A and B) in sympathetic ganglia from neonatal and adult rats. Both classes of ephs (A and B) and both classes of ephrins (A and B) bound to the cell bodies and neurites of dissociated postganglionic sympathetic neurons. Messenger RNAs encoding for both classes of ephs (A and B) and both classes of ephrins (A and B) were also detected in sympathetically innervated arteries from neonatal and adult rats. These data suggest that ephrins/ephs on nerve fibers of postganglionic sympathetic neurons could interact with ephs/ephrins on cells in innervated arteries. We found that ephA4 reduced reinnervation of denervated femoral arteries. Reinnervation in the presence of ephA4-Fc (38.9±6.6%) was significantly less than that in the presence of IgG-Fc (62±10%; n=5; p<0.05; one-tailed unpaired t-test). These data indicate that eph/ephrin interactions modulated the growth of vascular sympathetic innervation. We also found that ephA4 increased basal release of norepinephrine from nerve terminals of isolated tail arteries. These data indicate that eph/ephrin interactions affect the growth and function of vascular sympathetic innervation.

Peripheral mu-opioid receptors attenuate the augmented exercise pressor reflex in rats with chronic femoral artery occlusion.

Recently, opioid receptors have been shown to be expressed on group III and IV afferents, which comprise the sensory arm of the exercise pressor reflex. Although the stimulation of opioid receptors in the central nervous system has been shown to attenuate the exercise pressor reflex, the effect on the reflex of their stimulation in the periphery is unknown. We therefore tested the hypothesis that the activation of peripheral mu-opioid receptors attenuates the exercise pressor reflex. The pressor responses to static contraction were compared before and after the injection of the mu-opioid receptor agonist [d-Ala(2),N-MePhe(4),Gly-ol(5)]enkephalin (DAMGO; 1 microg) into the abdominal aorta of decerebrated rats in which one femoral artery had been occluded 72 h previously (n = 10) and in control rats whose femoral arteries were freely perfused (n = 8). DAMGO attenuated the peak pressor response to contraction in rats whose femoral arteries had been occluded (before: increase of 34 + or - 3 mmHg and after: increase of 22 + or - 2 mmHg, P = 0.008); the inhibitory effect of DAMGO was prevented by the injection of naloxone (100 microg) into the abdominal aorta (before: increase of 29 + or - 5 mmHg and after: increase of 29 + or - 5 mmHg, P = 0.646, n = 7). An intravenous injection of DAMGO (1 microg, n = 6) had no effect on the peak pressor response to contraction in both groups of rats. DAMGO had no effect on the peak pressor response to contraction in rats whose femoral arteries were freely perfused (before: Delta 23 + or - 4 mmHg, after: Delta 23 + or - 3 mmHg, n = 6) but appeared to have a small effect on topography of the response. DAMGO had no effect on the peak pressor response to tendon stretch in both groups of rats (both P > 0.05). We conclude that the stimulation of peripheral mu-opioid receptors attenuates the exercise pressor reflex in rats whose femoral arteries have been ligated for 72 h.

Age-related changes in the sympathetic innervation of cerebral vessels and in carotid vascular responses to norepinephrine in the rat: in vitro and in vivo studies.

We hypothesized that the density of sympathetic noradrenergic innervation of cerebral arteries and vasoconstrictor responses evoked in carotid circulation by norepinephrine (NE) increase with maturation and age. In rats of 4-5, 10-12, and 42-44 wk of age (juvenile, mature, middle aged), glyoxylic acid applied to stretch preparations showed the density of noradrenergic nerves in basilar and middle cerebral arteries was greater in mature than juvenile or middle-aged rats. In anesthetized rats, infusion of NE (2.5 mug/kg iv) increased mean arterial pressure (ABP) to approximately 180 mmHg in mature and middle-aged but to only approximately 150 mmHg in juveniles rats. Concomitantly, carotid blood flow (CBF) decreased in mature and middle-aged rats but remained constant in juveniles because carotid vascular conductance (CVC) decreased more in mature and middle-aged than juvenile rats. We also hypothesized that nitric oxide (NO) blunts cerebral vasoconstrictor responses to NE. Inhibition of NO synthase with l-NAME (10 mg/kg iv) induced similar increases in baseline ABP in each group, but larger decreases in CVC and CBF in mature and middle-aged than juvenile rats. Thereafter, the NE-evoked increase in ABP was similar in juvenile and mature but accentuated in middle-aged rats. Concomitantly, NE decreased CVC in juvenile and mature, but not middle-aged rats; in them, CBF increased. Thus, in juvenile rats, sparse noradrenergic innervation of cerebral arteries is associated with weak NE-evoked pressor responses and weak carotid vasoconstriction that allows autoregulation of CBF. Cerebral artery innervation density increases with maturation but lessens by middle age. Meanwhile, NE-evoked pressor responses and carotid vasoconstriction are stronger in mature and middle-aged rats, such that CBF falls despite the evoked increase in ABP. We propose that in juvenile and mature rats, NO does not modulate NE-evoked pressor responses, cerebral vasoconstriction, or CBF autoregulation, but by middle age, NO limits pressor responses and prevents breakthrough of CBF in the upper part of the autoregulatory range.

Retrograde arterial leg blood flow during tilt-back from a head-up posture: importance of capacitive flows when arterial pressure changes.

The windkessel function of the arterial system converts the intermittent action of the heart into more continuous microcirculatory blood flow during diastole via the return of elastic energy stored in the walls of the arteries during systole. Might the same phenomenon occur regionally within the arterial system during tilting owing to regional differences in local arterial pressure imposed by gravity? We sought to test the hypothesis that during tilt-back from a head-up posture, the return of stored elastic energy in leg arteries would work to slow, or perhaps transiently reverse, the flow of blood in the femoral artery. Femoral artery blood flow and arterial pressure were recorded during tilt back from a 30 degrees head-up posture to supine (approximately 0.5 G) in young, healthy subjects (n = 7 males and 3 females) before and during clonidine infusion. During control (no drug) conditions femoral artery blood flow ceased for an entire heart beat during tilt-back. During clonidine infusion femoral artery blood flow reversed for at least one entire heart beat during tilt-back, i.e., blood flow in the retrograde direction in the femoral artery from the leg into the abdomen. Thus substantial capacitive effects of tilting on leg blood flow occur in humans during mild changes in posture.

The applied anatomy of anterior approach for minimally invasive hip joint surgery.

The anterior approach for minimally invasive hip joint surgery is one of the common approaches utilized in hip joint surgery. Here, we report the results of dissections in 60 sides of human adult cadavers. We observed and measured the branches of the superficial circumflex iliac artery, the lateral femoral cutaneous nerves, the lateral circumflex femoral artery, and the superior gluteal nerves in the experiment via the anterior approach for minimally invasive hip joint surgery. The relationship between these structures and the anterior approach was studied. The present study provides important data demonstrating the location, path of dominant structures that might be encountered during the surgery and their relationships with the surgical incision. These data may allow surgeons performing the anterior approach for hip joint surgery to minimize the risk of neurovascular injury.