Increase In Femoral Vascular Resistance Research Articles

Functional sympatholysis (FS) in rats is graded with exercise but is not NO‐mediated

FS is the exercise attenuation of sympathetic vasoconstriction. It is unclear if NO is the major mediator of FS or if the size of FS is graded to the level of exercise. Experiments were performed on anaesthetised rats (under UK legislation). Sympathetic vasoconstriction was induced by stimulation of the lumbar sympathetic chain (LSC). EDL contraction was evoked and tension recorded; femoral vascular resistance (FVR) was calculated. Vasoconstriction was evoked during baseline and graded muscle contraction (10–30% max twitch) under control conditions, after NOS inhibition (L‐NAME) and following restoration of baseline (SNP infusion). LSC‐evoked vasoconstriction (an increase in FVR) was attenuated at all levels of muscle contraction. FS was graded and correlated to the peak force at each level. L‐NAME increased baseline FVR and the vasoconstriction, but had no effect on FS at any level of muscle contraction. SNP restored baseline FVR and the vasoconstriction ‐ FS was similar to control conditions. FS was graded to the peak level of muscle contraction, not the force recorded during the sympathetic stimulation per se. Manipulation of endogenous levels of NO changes the magnitude of sympathetic vasoconstriction but does not alter the extent of FS during any of the muscle contractions used. These results are similar to human studies (no role for NO) but differ from animal studies (role for NO; see Saltin et al, 2012).

The effect of short‐term exercise training on the skeletal muscle vascular response to sympathetic stimulation

The effect of 4 weeks of exercise training (ET) on skeletal muscle sympathetic vasoconstriction was investigated. It was hypothesized that vascular responsiveness to sympathetic stimulation would be increased following ET. Sprague-dawley rats were randomly assigned to sedentary (S: n=12), mild- (M: 20m.min−15% grade; n=13) or heavy-intensity (H: 40m.min−15% grade, n=8) ET groups. Rats were trained 5d.week−1 for 4 weeks with total training volume matched between ET groups. Rats were anesthetised and instrumented with indwelling catheters and a femoral artery flow probe. The vascular response to lumbar sympathetic chain stimulation delivered continuously at 2Hz or in patterns at 20 or 40Hz was determined. The change in femoral vascular resistance (FVR) was calculated and expressed in arbitrary resistance units (RU). Basal blood flow (S: 4±1, M: 3±1, H: 4±1 mL·min−1), MAP (S: 100±14, M: 90±14, H: 89±15 mmHg) and FVR (S: 33±15, M: 27±5, H: 25±7 mmHg.mL·min−1) were similar between groups (p>0.05). Lumbar chain stimulations produced a smaller (p<0.05) increase in FVR at all frequencies in S (2Hz: 7±3; 20Hz: 9±4; 40Hz: 11±5 RU) compared to M (2Hz: 14±4; 20Hz: 18±4; 40Hz: 18±6 RU) and H (2Hz: 21±4; 20Hz: 27±6; 40Hz: 28±4 RU). These data demonstrate that following ET, the vascular response to sympathetic stimulation was up-regulated in a manner dependent on the intensity of training stimulus. NSERC Canada.

Contribution of α2‐adrenoceptors and Y1 neuropeptide Y receptors to the blunting of sympathetic vasoconstriction induced by systemic hypoxia in the rat

There is evidence that sympathetically evoked vasoconstriction in skeletal muscle is blunted in systemic hypoxia, but the mechanisms underlying this phenomenon are not clear. In Saffan-anaesthetized Wistar rats, we have studied the role of α2-adrenoceptors and neuropeptide Y (NPY) Y1 receptors in mediating vasoconstriction evoked by direct stimulation of the lumbar sympathetic chain by different patterns of impulses in normoxia (N) and systemic hypoxia (H: breathing 8% O2). Patterns comprised 120 impulses delivered in bursts over a 1 min period at 40 or 20 Hz, or continuously at 2 Hz. Hypoxia attenuated the evoked increases in femoral vascular resistance (FVR) by all patterns, the response to 2 Hz being most affected (40 Hz bursts: N = 3.25 ± 0.75 arbitrary resistance units (RU); H = 1.14 ± 0.29 RU). Yohimbine (Yoh, α2-adrenoceptor antagonist) or BIBP 3226 (Y1-receptor antagonist) did not affect baseline FVR. In normoxia, Yoh attenuated the responses evoked by high frequency bursts and 2 Hz, whereas BIBP 3226 only attenuated the response to 40 Hz (40 Hz bursts: N + Yoh = 2.1 ± 0.59 RU; N + BIBP 3226 = 1.9 ± 0.4 RU). In hypoxia, Yoh did not further attenuate the evoked responses, but BIBP 3226 further attenuated the response to 40 Hz bursts. These results indicate that neither α2-adrenoceptors nor Y1 receptors contribute to basal vascular tone in skeletal muscle, but both contribute to constrictor responses evoked by high frequency bursts of sympathetic activity. We propose that in systemic hypoxia, the α2-mediated component represents about 50% of the sympathetically evoked constriction that is blunted, whereas the contribution made by Y1 receptors is resistant. Thus we suggest the importance of NPY in the regulation of FVR and blood pressure increases during challenges such as systemic hypoxia.

Acute Hypoxia Increases S100β Protein in Association with Blood Flow Redistribution away from Peripheral Circulations in Fetal Sheep

We investigated in fetal sheep during late gestation the effects of acute hypoxemia on fetal plasma S100beta protein concentrations and how these relate to fetal redistribution of blood flow and acid-base status. Under general anesthesia, five Welsh Mountain sheep fetuses were instrumented with vascular catheters, and transit-time flow transducers were implanted around a femoral artery and an umbilical artery. At least 5 d after surgery, fetuses were subjected to 1 h of normoxia, 0.5 h of hypoxemia, and 1 h of recovery. Hypoxemia induced significant falls in fetal pH(a), arterial oxygen pressure, acid-base excess, and [HCO(3)(-)], without alteration to arterial partial pressure of carbon dioxide. An increase in arterial blood pressure, a fall in heart rate, an increase in femoral vascular resistance, and a decrease in umbilical vascular resistance occurred in all fetuses. During hypoxemia, plasma S100beta increased significantly and remained elevated until the end of the protocol. Within individual fetuses, plasma S100beta correlated with femoral vascular resistance and pH. In contrast, no relationship was found between S100beta and umbilical vascular resistance. This study reports for the first time that a controlled period of fetal hypoxemia with associated acidemia leads to persistent elevations in plasma S100beta concentrations that strongly correlate with hemodynamic changes that are known to occur during fetal blood flow redistribution. These findings open up a new role for changes in fetal S100beta concentrations as a possible early marker of fetal hypoxia with associated acidemia in perinatal medicine.

Differential responses to CO2 and sympathetic stimulation in the cerebral and femoral circulations in humans

The relative importance of CO2 and sympathetic stimulation in the regulation of cerebral and peripheral vasculatures has not been previously studied in humans. We investigated the effect of sympathetic activation, produced by isometric handgrip (HG) exercise, on cerebral and femoral vasculatures during periods of isocapnia and hypercapnia. In 14 healthy males (28.1 +/- 3.7 (mean +/- S.D.) years), we measured flow velocity (VP; transcranial Doppler ultrasound) in the middle cerebral artery during euoxic isocapnia (ISO, +1 mmHg above rest) and two levels of euoxic hypercapnia (HC5, end-tidal P(CO(2)), P(ET,CO2), = +5 mmHg above ISO; HC10, P(ET,CO2) = +10 above ISO). Each P(ET,CO2) level was maintained for 10 min using the dynamic end-tidal forcing technique, during which increases in sympathetic activity were elicited by a 2-min HG at 30% of maximal voluntary contraction. Femoral blood flow (FBF; Doppler ultrasound), muscle sympathetic nerve activity (MSNA; microneurography) and mean arterial pressure (MAP; Portapres) were also measured. Hypercapnia increased VP and FBF by 5.0 and 0.6% mmHg-1, respectively, and MSNA by 20-220%. Isometric HG increased MSNA by 50% and MAP by 20%, with no differences between ISO, HC5 and HC10. During the ISO HG there was an increase in cerebral vascular resistance (CVR; 20 +/- 11%), while VP remained unchanged. During HC5 and HC10 HG, VP increased (13% and 14%, respectively), but CVR was unchanged. In contrast, HG-induced sympathetic stimulation increased femoral vascular resistance (FVR) during ISO, HC5 and HC10 (17-41%), while there was a general decrease in FBF below ISO. The HG-induced increases in MSNA were associated with increases in FVR in all conditions (r = 0.76-0.87), whereas increases in MSNA were associated with increases in CVR only during ISO (r = 0.91). In summary, in the absence of hypercapnia, HG exercise caused cerebral vasoconstriction, myogenically and/or neurally, which was reflected by increases in CVR and a maintained VP. In contrast, HG increased FVR during conditions of ISO, HC5 and HC10. Therefore, the cerebral circulation is more responsive to alterations in PCO2, and less responsive to sympathetic stimulation than the femoral circulation.

Cortisol and ACTH responses to severe asphyxia in preterm fetal sheep

It has been hypothesized that the hypothalamic-pituitary-adrenal (HPA) axis is immature in the preterm fetus and that this compromises their ability to adapt to hypoxic stress; however, there are few direct data. We therefore examined the effects of asphyxia on HPA responses in chronically instrumented preterm fetal sheep (104 days of gestation; term is 147 days), allocated to a sham control group (n = 7) or 25 min of complete umbilical cord occlusion (n = 8), followed by recovery for 72 h. During umbilical cord occlusion there was a rapid rise in ACTH levels (230.4 +/- 63.5 versus 14.1 +/- 1.8 ng ml(-1) in sham controls, 16-fold) and cortisol levels (7.4 +/- 4.9 versus 0.2 +/- 0.1 ng ml(-1), 31-fold), with further increases after release of cord occlusion. ACTH levels were normalized by 24 h, while plasma cortisol levels returned to sham control values 72 h after asphyxia. Fetal arterial blood pressure was elevated in the first 36 h, with a marked increase in femoral vascular resistance, and correlated positively with cortisol levels after asphyxia (P = 0.05). In conclusion, the preterm fetus shows a brisk, substantial HPA response to severe hypoxia.

Influence of endogenous nitric oxide on sympathetic vasoconstriction in normoxia, acute and chronic systemic hypoxia in the rat.

We studied the role of nitric oxide (NO) in blunting sympathetically evoked muscle vasoconstriction during acute and chronic systemic hypoxia. Experiments were performed on anaesthetized normoxic (N) and chronically hypoxic (CH) rats that had been acclimated to 12% O(2) for 3-4 weeks. The lumbar sympathetic chain was stimulated for 1 min with bursts at 20 or 40 Hz and continuously at 2 Hz. In N rats, acute hypoxia (breathing 8% O(2)) reduced baseline femoral vascular resistance (FVR) and depressed increases in FVR evoked by all three patterns of stimulation, but infusion of the NO donor sodium nitroprusside (SNP), so as to similarly reduce baseline FVR, did not affect sympathetically evoked responses. Blockade of NO synthase (NOS) with L-NAME increased baseline FVR and facilitated the sympathetically evoked increases in FVR, but when baseline FVR was restored by SNP infusion, these evoked responses were restored. Acute hypoxia after L-NAME still reduced baseline FVR and depressed evoked responses. In CH rats breathing 12% O(2), baseline FVR was lower than in N rats breathing air, but L-NAME had qualitatively similar effects on baseline FVR and sympathetically evoked increases in FVR. SNP similarly restored baseline FVR and evoked responses. Inhibition of neuronal NOS or inducible NOS did not affect baselines, or evoked responses. We propose that in N and CH rats sympathetically evoked muscle vasoconstriction is modulated by tonically released NO, but not depressed by additional NO released on sympathetic activation. The present results suggest that hypoxia-induced blunting of sympathetic vasoconstriction in skeletal muscle is not mediated by NO.

Contribution of adenosine to the depression of sympathetically evoked vasoconstriction induced by systemic hypoxia in the rat.

Previous studies have shown that systemic hypoxia evokes vasodilatation in skeletal muscle that is mediated mainly by adenosine acting on A1 receptors, and that the vasoconstrictor effects of sympathetic nerve activity are depressed during hypoxia. The aim of the present study was to investigate the role of adenosine in this depression. In anaesthetised rats, increases in femoral vascular resistance (FVR) evoked by stimulation of the lumbar sympathetic chain with bursts of impulses at 40 or 20 Hz were greater than those evoked by continuous stimulation at 2 Hz with the same number of impulses (120) over 1 min. All of these responses were substantially reduced by infusion of adenosine or by graded systemic hypoxia (breathing 12, 10 or 8 % O2), increases in FVR evoked by continuous stimulation at 2 Hz being most vulnerable. Blockade of A1 receptors ameliorated the depression caused by adenosine infusion of the increase in FVR evoked by 2 Hz only and did not ameliorate the depression caused by 8 % O2 of increases in FVR evoked by any pattern of sympathetic stimulation. A2A receptor blockade accentuated hypoxia-induced depression of the increase in FVR evoked by burst stimulation at 40 Hz, but had no other effect. Neither A1 nor A2A receptor blockade affected the depression caused by hypoxia (8 % O2) of the FVR increase evoked by noradrenaline infusion. These results indicate that endogenously released adenosine is not responsible for the depression of sympathetically evoked muscle vasoconstriction caused by systemic hypoxia; adenosine may exert a presynaptic facilitatory influence on the vasoconstrictor responses evoked by bursts at high frequency.

Betamethasone-mediated vascular dysfunction and changes in hematological profile in the ovine fetus.

Glucocorticoid administration to fetal sheep induces a sustained systemic blood pressure rise and an associated increase in femoral vascular resistance. We utilized a small vessel myograph to compare isometric vascular responses of small femoral arterial branches from fetal sheep infused intravenously with either betamethasone or vehicle in vivo from 128 days gestation. Changes in hematological parameters were also determined. Betamethasone was infused for 48 h to produce fetal plasma betamethasone concentrations similar to those observed in human fetuses after maternal treatment with betamethasone to accelerate fetal lung maturation. When compared with vessels removed from vehicle-infused fetuses, vessels obtained from betamethasone-treated fetuses exhibited 1) enhanced sensitivity to depolarizing potassium solutions; 2) no differences in response to the thromboxane mimetic U-46619 or norepinephrine; and 3) differential responses to vasodilators, enhanced sensitivity to ACh, but decreased response to bradykinin and forskolin. In addition, erythrocyte and leukocyte counts were increased in betamethasone-infused fetuses. These observations indicate that multiple mechanisms operate to increase fetal vascular resistance during antenatal betamethasone exposure.

Effect of carotid denervation on plasma vasopressin levels during acute hypoxia in the late‐gestation sheep fetus.

1. We measured plasma concentrations of arginine vasopressin (AVP), arterial, venous and amniotic pressures, and carotid and femoral blood flows in fifteen chronically instrumented fetal sheep at 119-125 days of gestation. In eight of the fetuses the carotid sinus nerves were cut (denervated fetuses); the other seven remained intact and served as controls (intact fetuses). 2. In the intact fetuses during hypoxia there was an increase in plasma [AVP] and in perfusion (arterial-venous) pressure, a transient bradycardia, and an increase in carotid and a decrease in femoral blood flow. Whilst femoral vascular resistance (perfusion pressure/femoral blood flow) increased, there were no changes in carotid vascular resistance during hypoxia. 3. In the denervated fetuses no significant bradycardia, fall in femoral blood flow or increase in femoral vascular resistance was present soon after the onset of hypoxia but plasma AVP increased to similar concentrations to those observed in intact fetuses during hypoxia. 4. We conclude that carotid denervation does not affect plasma [AVP] during hypoxia in fetal sheep. This suggests that (1) AVP release during hypoxia is not mediated by a carotid chemoreflex and (2) AVP does not play an important role in these initial fetal cardiovascular responses. Furthermore, we previously reported that intact fetuses survive acute hypoxia better than denervated fetuses following phentolamine treatment, and we believe this to be due to the action of a non-alpha-adrenergic vasoconstrictor released in part via a carotid chemoreflex. The present results suggest that this vasoconstrictor is not AVP.

Renal versus femoral hemodynamic response to endothelium-derived relaxing factor synthesis inhibition.

Systemic inhibition of endothelium-derived relaxing factor (EDRF) synthesis leads to acute hypertension and increased peripheral vascular resistance. The changes in vascular resistance are not evenly distributed to all vascular beds. In this study, we compared the renal and femoral hemodynamic responses to EDRF synthesis inhibition. Renal blood flow (RBF) and femoral blood flow (FBF) were assessed in the presence and absence of DuP 753, an angiotensin II receptor antagonist. Inhibition of EDRF synthesis by a bolus dose of Lw-nitroarginine methyl ester (L-NAME) increased blood pressure (BP) by 21 +/- 1 mm Hg (p < 0.001) and decreased RBF by 32 +/- 5% (from 5.9 +/- 0.5 to 3.9 +/- 0.3 ml/min/g kidney weight; p < 0.005) while FBF remained unchanged (9.5 +/- 0.4 versus 9.4 +/- 0.4 ml/min). Renal vascular resistance (RVR) increased by 83 +/- 16% (p < 0.001), compared with only a 24 +/- 6% increase in femoral vascular resistance (FVR; p < 0.005). To eliminate the influence of systemic hypertension, we returned organ perfusion pressure to pre-L-NAME levels by partial aortic constriction. The kidney maintained RBF by decreasing RVR by 8 +/- 2% (p < 0.02), while FBF decreased by 15 +/- 5% (p < 0.01). When rats were pretreated with DuP 753, L-NAME still increased BP by 22 +/- 2 mm Hg, but RVR increased by only 26 +/- 5% (from 13.2 +/- 1.6 to 16.8 +/- 2.7; p < 0.01) and RBF did not change. DuP 753 had no effect on the femoral vascular response to L-NAME.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiovascular-respiratory reflex interactions between carotid bodies and upper-airways receptors in the monkey

The carotid bodies were stimulated in the anesthetized pig-tailed macaque monkey (Macaca nemestrina) using i) brief injections of cyanide or CO2-equilibrated bicarbonate solution into a common carotid artery, and ii) longer perfusion with hypoxic hypercapnic blood in vascularly isolated chemoreceptor preparations. In spontaneously breathing animals, brief stimulations of the chemoreceptors consistently caused an increase in pulmonary ventilation, bradycardia, and an increase in femoral vascular resistance. When the same chemoreceptor stimulus was superimposed during the apneic period, reflexly evoked by stimulating either the central ends of the superior laryngeal nerves or the nasopharynx, the respiratory stimulation was absent or minimal, but the bradycardia and vasconstriction were greatly enhanced and exceeded the summed responses of separate stimulation of the chemoreceptors and one or the other of the upper-airways inputs. With sustained stimulation of the carotid bodies, hyperventilation, tachycardia, and femoral vasodilatation occurred due to overriding respiratory mechanisms. When superior laryngeal nerve stimulation was superimposed on this response, apnea occurred and tachycardia was reversed to bradycardia, and femoral vascular resistance increased above resting level. The interaction of autonomic responses resulting from chemoreceptor stimulation and from increases in the upper-airways inputs are qualitatively similar in the monkey and in subprimate species. Those involving specifically cardioinhibitory vagal responses are, in part at least, dependent on mechanisms related to the concomitant changes in respiration.

Attenuation of postganglionic sympathetic nerve activity by L-dopa.

In anesthetized dogs and cats, intravenous L-dopa reduced the increase in mean blood pressure in response to bilateral carotid occlusion by 77.5% ( P &lt;0.01). In the presence of a dopa decarboxylase inhibitor (Ro 4·4602), this effect was absent. Transmission across the superior cervical sympathetic ganglion in the cat was unaltered by the administration of L-dopa. Carotid artery infusion in the dog of 20% of the effective intravenous dose of L-dopa or dopamine failed to inhibit the response to bilateral carotid occlusion. The pressor response to intravenous tyramine in the dog was potentiated ( P &lt;0.05) by L-dopa. In the dog, the increase in femoral vascular resistance to lumbar sympathetic nerve stimulation was attenuated ( P &lt;0.05) by L-dopa while the response to intra-arterial norepinephrine was unchanged. Thus, inhibition of postganglionic sympathetic nerve activity is a possible mechanism by which L-dopa impaired the carotid sinus reflex.