Frequency modulation of mesenteric and renal vascular resistance

The hypothesis was tested that low-frequency vasomotions in individual vascular beds are integrated by the cardiovascular system, such that new fluctuations at additional frequencies occur in arterial blood pressure. In anesthetized rats (n = 8), the sympathetic splanchnic and renal nerves were simultaneously stimulated at combinations of frequencies ranging from 0.075 to 0.8 Hz. Blood pressure was recorded together with mesenteric and renal blood flow velocities. Dual nerve stimulation at low frequencies (<0.6 Hz) caused corresponding oscillations in vascular resistance and blood pressure, whereas higher stimulation frequencies increased the mean levels. Blood pressure oscillations were only detected at the individual stimulation frequencies and their harmonics. The strongest periodic responses in vascular resistance were found at 0.40 +/- 0.02 Hz in the mesenteric and at 0.32 +/- 0.03 Hz (P < 0.05) in the renal vascular bed. Thus frequency modulation of low-frequency vasomotions in individual vascular beds does not cause significant blood pressure oscillations at additional frequencies. Furthermore, our data suggest that sympathetic modulation of mesenteric vascular resistance can initiate blood pressure oscillations at slightly higher frequencies than sympathetic modulation of renal vascular resistance.     

Skeletal muscle vasoconstriction produced by prostaglandin synthesis inhibitors; dependence on pump perfusion

A comparison was made of the effect of prostaglandin synthesis inhibitors (PGSI) on systemic blood pressure and hindlimb muscle vascular resistance of anesthetized dogs under different experimental conditions. When muscle blood flow was monitored using an extracorporeal or noncannulating electromagnetic blood flow probe, indomethacin (5 mg/kg i.v.) increased blood pressure slightly, but did not change vascular resistance. Administration of PGSI (indomethacin, meclofenamate, or naproxen, 5 mg/kg i.v.) after 2 hr of pump perfusion of the hindlimb caused a 22% increase in blood pressure, and 39% increase in vascular resistance 30 min afterwards. When administered immediately after instituting pump perfusion, indomethacin caused no significant change in blood pressure or vascular resistance at the 30 min interval, but at 60 min vascular resistance was increased. A similar vasoconstrictor response to indomethacin was obtained when it was infused in a lower dose intraarterially to the hindlimb, or when given i.v. after ligation of the renal pedicles. The results indicate that pump perfusion results in elaboration of a nonrenal prostaglandin(s) which maintains a vasodilator influence on the skeletal muscle vascular bed.     

Phrenic blood flow in cats with closed abdominal cavity]

By means of ultrasonic method, used in acute experiments on cats with closed abdominal cavity under nembutal narcosis, the authors studied the linear and volumetric blood flow velocity in left phrenic artery, the resistance of vascular bed of the phrenic artery, systemic blood pressure, respiration excursions during asphyxia, hypoxia, infusion of some biologically active substances. It was shown, that shortening of the diaphragm has definite influence on the blood flow and resistance of the vascular bed of the phrenic artery; the degree of the decrease of the blood flow in inspiration (on relation to the value of the blood flow in expiration, that passed as 100%) does not differ significantly in quiet and intensive respiration. Under the influences, the resistance of vascular bed of the phrenic artery decreases, the linear and volumetric blood flow increases, that indicates large reserve of the vascular bed of the phrenic artery for the increase of the blood flow.     

The influence of muscular contractions on acetylcholine effects on nutritive blood flow in the hindpaw of dog.

In the earlier investigations it was shown that muscular exercise augmented the dilator effects of ACh in the vascular bed of the hind leg of dog. To get a closer insight into this phenonenon the effects of acetylcholine on the nutritive blood flow in contracting skeletal muscle in the dog were studied. It was found that i.a. acetylcholine administration raises the nutritive blood flow in the investigated vascular bed within about 30--36 minutes after muscular contractions. The nutritive blood flow during and following muscular contractions induced by stimuli of varying frequency was also investigated.     

Stroma-free hemoglobin: its presence in plasma does not improve oxygen supply to the resting hindlimb vascular bed of hemodiluted dogs.

In hemodilution, red cell spacing in the microcirculation is increased, flow distribution may become more heterogeneous, and, as a result, oxygen supply to tissues may suffer. We tested the hypothesis that oxygen extraction from diluted blood may be enhanced by the presence of hemoglobin in the plasma phase in relatively low concentrations. In anesthetized dogs, the hindlimb vascular bed was isolated and perfused with the animal's own blood by a roller pump. One group of dogs (n = 6) was hemodiluted (hematocrit = 15.0 +/- 1.0%) with a 6% solution of dextran. A second group of dogs (n = 6) was similarly hemodiluted (hematocrit = 16.0 +/- 0.4%) with dextran containing stroma-free hemoglobin solution whereby plasma-phase hemoglobin concentration was raised to 1.1 +/- 0.1 g.dL-1. Systemic hemodynamic observations were made repeatedly over the subsequent 2.5 h, while blood flow to the hindlimb was progressively reduced in stepwise decrements. The hemoglobin-hemodiluted group showed increased systemic arterial blood pressure and total peripheral resistance when compared with the control (dextran diluted) group. The isolated hindlimb also showed evidence of increased vascular resistance in the hemoglobin-treated group. In each individual animal, critical oxygen delivery and extraction were determined by finding the intercept of the supply-independent and supply-dependent portions of the oxygen uptake/oxygen delivery relationship. Neither the critical oxygen delivery rates (5.75 +/- 0.83 vs. 6.41 +/- 0.53 mL.kg-1.min-1) nor critical oxygen extraction ratios (0.75 +/- 0.03 vs. 0.76 +/- 0.04) were found to be significantly different in the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

Muscle pump function during locomotion: mechanical coupling of stride frequency and muscle blood flow

We imposed opposing oscillations in treadmill speed and grade on nine rats to test for direct mechanical coupling between stride frequency and hindlimb blood flow. Resting hindlimb blood flow was 15.5 +/- 1.7 ml/min. For 90 s at 7.5 m/min, rats alternated walking at -10 degrees for 10 s and +10 degrees for 10 s. This elicited oscillations in hindlimb blood flow having an amplitude of 4.1 +/- 0.5 ml/min (18% of mean flow) with a delay presumably due to metabolic vasodilation. Similar oscillations in speed (5.5-9.5 m/min) elicited oscillations in hindlimb blood flow (amplitude 3.4 +/- 0.5 ml/min, 15% of mean flow) with less of a delay, possibly due to changes in vasodilation and muscle pump function. We then simultaneously imposed these speed and grade oscillations out of phase (slow uphill, fast downhill). The rationale was that the oscillations in vasodilation evoked by the opposing oscillations in speed and grade would cancel each other, thereby testing the degree to which stride frequency affects hindlimb blood flow directly (i.e., muscle pumping). Opposing oscillations in speed and grade evoked oscillations in hindlimb blood flow having an amplitude of 3.3 +/- 0.6 ml/min (16% of mean flow) with no delay and directly in phase with the changes in speed and stride frequency. The finding that hindlimb blood flow changes directly with speed (when vasodilation caused by changes in speed and grade oppose each other) indicates that there is a direct coupling of stride frequency and hindlimb blood flow (i.e., muscle pumping).     

Assessment of the changes in regulatory systems of human's skin blood flow during local heating

The mechanisms of thermal regulation of skin blood flow during local heating to 35, 40 and 45 'C have been studied by the method of laser Doppler flowmetry in healthy volunteers. To estimate the state of microvascular bed the continuous wavelet-transform spectral analysis has been used. The amplitudes of fluxmotions in the range of blood flow active modulation significantly increase during local heating to 35 degrees C. The amplitudes of blood flow oscillations in the ranges of cardiorhythm and respiratory rhythm increase during local heating to 40 degrees C. The high amplitude oscillations in the range of myogenic activity are maintained. The amplitude of oscillations in the range of endothelial activity distinctly decreases and the oscillations in the range of neurogenic activity are inhibited. Local heating to 45 degrees C results in a significant decreasing of the oscillation amplitudes in the range of myogenic activity, and the amplitudes of cardio- and respiratory spectral components amount to their peak values among the temperatures of local heating under study.     

Comparative responses to endothelin-2 and sarafotoxin 6b in the pulmonary vascular bed of the cat

Pulmonary vascular responses to endothelin-2 and sarafotoxin 6b were investigated in the feline pulmonary vascular bed under natural flow and constant flow conditions. Injections of endothelin-2 and sarafotoxin 6b in a dose of 0.3 nmol/kg iv increased pulmonary arterial and left atrial pressures and cardiac output, and caused a biphasic change in calculated pulmonary vascular resistance. Endothelin-2 caused a biphasic change in systemic arterial pressure, while sarafotoxin 6b only decreased arterial pressure. Under constant flow conditions in the intact-chest cat, injections of endothelin-2 and sarafotoxin 6b in doses of 0.1-1 nmol into the perfused lobar artery increased lobar arterial pressure in a dose-related manner but were less potent than the thromboxane A2 mimic, U46619. An ET analog with only the Cys1-Cys15 disulfide bond and an amidated carboxy terminus had no significant activity in the pulmonary vascular bed. The present data show that endothelin-2 and sarafotoxin 6b have significant vasoconstrictor activity in the pulmonary vascular bed of the cat.     

The problem of adaptation and oscillatory processes in the microvascular bed

Healthy people (n = 16), patients with autonomic dystonia syndrome (n = 38), and patients with traumatic rupture of the median nerve before and after nerve suture (n = 28) were examined by laser Doppler flowmetry (LDF) with a computer wavelet analysis of blood flow oscillations. Functional states (FSs) of the microcirculatory bed wеre assessed using energetic and information indices of microvascular blood flow oscillations. The variation coefficient and the information regime (multistable or resonance) were used as key characteristics. Oscillatory processes are an integral part of adaptation and the FS formation in the microvascular bed. FSs were classified as adaptive, hyperadaptive, hypoadaptive, and failure of adaptation. Because supporting the optimal function of nutritive microvessels is a leading component of the adaptation process, FSs of nutritive and nonnutritive microvessels may differ. A selective contribution of the autonomic sympathetic regulatory channel was related to maintaining considerable hyperadaptation in the microvascular bed with overstrain or marked overstrain of regulatory systems, as in emotional stress. Hypoadaptive FSs formed when skin blood flow increased, an excess decrease in flow resistance was unnecessary, and especially when regulatory factors were in deficiency, e.g., in neurodystrophic syndrome.     

Skeletal muscle blood bed in growing rats

Morphometric study of vascular bifurcations and capillaries in biceps femoris artery basin was performed in 2-week old, 1-month old, and adult Wistar rats. Proceeding from the results, the blood tree was digitally reconstructed, and the main haemodynamic parameters in digital simulation were evaluated in this vascular bed: the blood flow velocity, wall shear stress, drop of perfusion pressure, and resistance. The comparison with a similar study of cerebral vascular bed revealed peculiarities of the vascular bed formation and intraorgan haemodynamics in these organs.     

A nonlinear dynamic approach reveals a long-term stroke effect on cerebral blood flow regulation at multiple time scales

Cerebral autoregulation (CA) is an important vascular control mechanism responsible for relatively stable cerebral blood flow despite changes of systemic blood pressure (BP). Impaired CA may leave brain tissue unprotected against potentially harmful effects of BP fluctuations. It is generally accepted that CA is less effective or even inactive at frequencies >∼0.1 Hz. Without any physiological foundation, this concept is based on studies that quantified the coupling between BP and cerebral blood flow velocity (BFV) using transfer function analysis. This traditional analysis assumes stationary oscillations with constant amplitude and period, and may be unreliable or even invalid for analysis of nonstationary BP and BFV signals. In this study we propose a novel computational tool for CA assessment that is based on nonlinear dynamic theory without the assumption of stationary signals. Using this method, we studied BP and BFV recordings collected from 39 patients with chronic ischemic infarctions and 40 age-matched non-stroke subjects during baseline resting conditions. The active CA function in non-stroke subjects was associated with an advanced phase in BFV oscillations compared to BP oscillations at frequencies from ∼0.02 to 0.38 Hz. The phase shift was reduced in stroke patients even at > = 6 months after stroke, and the reduction was consistent at all tested frequencies and in both stroke and non-stroke hemispheres. These results provide strong evidence that CA may be active in a much wider frequency region than previously believed and that the altered multiscale CA in different vascular territories following stroke may have important clinical implications for post-stroke recovery. Moreover, the stroke effects on multiscale cerebral blood flow regulation could not be detected by transfer function analysis, suggesting that nonlinear approaches without the assumption of stationarity are more sensitive for the assessment of the coupling of nonstationary physiological signals.     

Cardio- and hemodynamics of dogs in exposure of the heart to immune complexes

The cardiovascular effects induced by in-vitro obtained immune complexes (horse serum antigens--rabbit specific antibodies) were studied in dogs. Intracoronary administration of immune complexes was followed by the development of a hypotensive reaction, with a marked decrease in the cardiac output, left ventricle performance, and impairment of pump heart function. After administering immune complexes no marked injuries to the myocardium or depression of its contractility were recorded in the acute period of the reaction. A substantial decrease of venous blood return to the heart caused by blood pooling in the venous peripheral vascular bed underlies pump heart function impairment and the decreased cardiac output.     

Effects of 13, 14-dehydroprostacyclin methyl ester on the feline intestinal vascular bed.

The effects of a stable PGI2 analog, 13, 14-dehydro-PGI2 methyl ester and several vasoactive hormones were compared in the feline intestinal vascular bed under conditions of controlled blood flow so that changes in perfusion pressure directly reflect changes in vascular resistance. The PGI2 analog decreased perfusion pressure in a dose-dependent fashion when injected in the range of dose of 0.03-3 microgram and was quite similar to PGE2 whereas isoproterenol was somewhat more potent as a vasodilagor in the feline intestinal vascular bed. The present data show that 13, 14-dehydro-PGI2 methyl ester has potent vasodilator activity in the intestinal vascular bed.     

Synthetic human adrenomedullin and ADM15-52 have potent short-lasting vasodilator activity in the pulmonary vascular bed of the cat

Responses to synthetic human adrenomedullin, a novel hypotensive peptide localized in several organ systems, including the lung, and the carboxy terminal 15-52 amino acid fragment of adrenomedullin (ADM15-52) were investigated in the pulmonary vascular bed of the intact-chest cat. Under constant flow conditions when baseline tone in the pulmonary vascular bed was raised to a high steady level, injections of adrenomedullin and ADM15-52 into the perfused lobar artery in doses of 0.1-1 nmol, caused significant doserelated decreases in lobar arterial pressure. Since left atrial pressure was unchanged, the decreases in lobar arterial pressure reflect decreases in pulmonary lobar vascular resistance. Adrenomedullin and ADM15-52 exhibited similar vasodilator activity and were approximately 3-fold more potent than bradykinin in the pulmonary vascular bed of the cat. Pulmonary vasodilator responses to adrenomedullin and ADM15-52 were rapid in onset and laster for 150–200 sec, depending on the dose of the peptide injected. The present results demonstrate that synthetic human adrenomedullin and ADM15-52 possess potent, short-lasting vasodilator activity in the pulmonary vascular bed of the cat and suggest that amino acids 15-52 in the peptide are important for the expression of vasodilator activity in the pulmonary vascular bed of the cat.     

Interaction of the formed elements of blood with the coronary vasculature in vivo

Considerable attention is being given to the interactions that occur among blood platelets, neutrophils, and the vascular endothelium. There is an increasing awareness that the various blood elements interact in the process of thrombus formation and vascular occlusion. In addition, interactions among these cells can lead to the formation and release of vasoactive substances that have the potential to modulate regional blood flow. This review focuses on the coronary vascular bed and an assessment of how cell-cell interactions, under normal physiological conditions as well as in the presence of myocardial injury, may lead to alterations in coronary vascular resistance and myocardial function. Should related events be operative in human clinical states of disease, the circulating elements of the blood may serve as targets in the development of therapeutic interventions to regulate myocardial blood flow.     

Role of mechanosensitivity of the endothelium in weakening of the vascular bed vasoconstriction

The effect of control of arterial diameter by the shear stress at the endothelium on noradrenaline-induced constriction of femoral vascular bed was investigated in anaesthetised cats. We compared noradrenaline-induced responses during the perfusion of the hindlimb at a constant blood flow and at a constant pressure as vasoconstriction is accompanied by an increase in wall shear stress only in the former case. We found that the same concentration of noradrenaline at a constant flow caused an augmentation of vascular resistance that was considerably smaller than at a constant pressure perfusion. This difference was almost eliminated after either removal of the endothelium or selective impairment of the endothelial sensitivity to the shear stress. These findings demonstrate that the control of arterial smooth muscle tone at a constant blood flow by shear stress at the endothelium does weaken noradrenaline-induced vasoconstriction.     

Arteriovenous oscillations of the redox potential: Is the redox state influencing blood flow?

Objective: Studies on the regulation of human blood flow revealed several modes of oscillations with frequencies ranging from 0.005 to 1 Hz. Several mechanisms were proposed that might influence these oscillations, such as the activity of vascular endothelium, the neurogenic activity of vessel wall, the intrinsic activity of vascular smooth muscle, respiration, and heartbeat. These studies relied typically on non-invasive techniques, for example, laser Doppler flowmetry. Oscillations of biochemical markers were rarely coupled to blood flow.

Methods: The redox potential difference between the artery and the vein was measured by platinum electrodes placed in the parallel homonymous femoral artery and the femoral vein of ventilated anesthetized pigs.

Results: Continuous measurement at 5 Hz sampling rate using a digital nanovoltmeter revealed fluctuating signals with three basic modes of oscillations: ～ 1, ～ 0.1 and ～ 0.01 Hz. These signals clearly overlap with reported modes of oscillations in blood flow, suggesting coupling of the redox potential and blood flow.

Discussion: The amplitude of the oscillations associated with heart action was significantly smaller than for the other two modes, despite the fact that heart action has the greatest influence on blood flow. This finding suggests that redox potential in blood might be not a derivative but either a mediator or an effector of the blood flow control system.     

The role of the endothelium in the vascular effects of vintoperol]

The effects of vintoperol have been studied in the experiments on the vascular bed of femoral artery of 15 mongrel dogs under chlorazol-urethane narcosis and on isolated vascular preparations of rats. It is shown that ++de-endothelization of vascular bed using saponin and mechanical removal of endothelial stripes decreased the vasodilatation reaction and relaxation of stripes by 50-60% of the initial values. While infusing ventoperol (0.3 mg.kg-1 min-1) to ++de-endothelized vascular bed, the blood flow increased by 18 +/- 5% as against 47 +/- 3.9% of the initial value under intact endothelium. Blockade of guanylate cyclase by methylene blue decreased blood flow under vintoperol action to 24 +/- 3.5%. The similar results are obtained in the experiments in vitro. After ++de-endothelization of pulmonary artery++ the amplitude of relaxation of preactivated smooth muscles decreased vs. initial tone (21 +/- 3.7% vs. 56% +/- 5.3%). Inhibition of relaxation reaction of vascular stripe under vintoperol effect is also observed after treatment with gossypol, or methylene blue. Thus, endothelium is involved in the realization of vasodilating effect of vintoperol, its action being mediated by endothelium--derived relaxing factor.     

Resistance and capacitance functions of gastric vessels under the action of noradrenaline

In acute experiments on cats, the gastric vascular bed being perfused under constant blood flow, the actions of gastric vessels was investigated using newly elaborated approach to their humoral isolation. Increased doses of noradrenaline elicited the dose-dependent constrictive response of gastric arterial vessels. Perfusion pressure increase in the gastric vascular bed under action of the minimal dose of noradrenaline was more pronounced, than in the intestinal vessels. The capacity of the gastric vascular bed under action of the drug changed in different manner, mostly increased, but could be decreased as well. In contrast to the small intestine the gastric vessels are characterized by more pronounced action of noradrenaline on blood depoting processes.     

Uterine blood flow in the pregnant rabbit.

Two methods are described for the measurement of uterine blood flow in the pregnant rabbit. The first involves the use of a Parks ultrasonic Doppler probe placed over the exposed uterine artery. The second method uses a drop counter system connected between the uterine and jugular veins. The Doppler flowmeter was used to measure uterine arterial blood flow in twenty rabbits on Day 28 or 29 of pregnancy. No significant difference was observed between blood flow on these 2 days and the absolute blood flow to one horn (plus or minus S. E.) was found to be 16.8 plus or minus 1.4 ml/min, equivalent to 27.1 plus or minus 1.8 ml/100 g tissue/min. Using the drop recorder technique, the flow to one uterine horn in eleven rabbits on Day 27 or 28 of pregnancy was 12.5 plus or minus 1.9 ml/min, equivalent to 23.6 plus or minus 3.2 ml/100 g tissue/min. The pressure-flow relationship in the uterine vascular bed was studied using the Doppler flowmeter and graded mechanical occlusion of the arterial supply. Within the range of pressures studied, the flow was found to be linearly related to the arterio-venous pressure difference. This suggests that the uterine vascular bed was fully dilated under the conditions of study.