Changes In Arteriolar Diameter Research Articles

Effect of inosine on pial arterioles: potentiation of adenosine-induced vasodilation.

We examined the cerebral vasoactivity of inosine and its effect on pial arteriolar vasodilation induced by adenosine. Pial circulation was observed through cranial windows implanted in rats anesthetized with halothane. No significant change in venous or arteriolar diameter was apparent when inosine (10(-6) to 10(-3) M) was superfused. In contrast, adenosine in concentrations of 10(-7) and 10(-6) M dilated pial arterioles by 9.0 +/- 1.2 and 17.7 +/- 1.7%, respectively. Addition of 10(-5) M inosine had no effect, whereas 10(-4) M inosine enhanced the vasodilation induced by 10(-7) M adenosine to 19.4 +/- 1.7% and that by 10(-6) M adenosine to 23.3 +/- 2.3%. When theophylline (5 X 10(-5) M) was perfused together with 10(-7) M adenosine and 10(-4) M inosine, the vasodilation was almost completely abolished. The present study indicates that inosine alone does not affect pial vessel diameter but potentiates the response of pial arterioles to exogenous adenosine. This potentiating action of inosine may be attributed to an increase in perivascular adenosine and may be explained by the action of inosine as an adenosine uptake inhibitor.

Microvascular actions of platelet-activating factor on rat gastric mucosa and submucosa.

Intravenous infusion of platelet-activating factor (PAF or AGEPC) induces extensive acute hemorrhagic damage in the ra gastric mucosa. The effects of PAF have now been investigated on several microcirculatory parameters in the rat gastric mucosa. Infusion of PAF (25-100 ng X kg-1 X min-1 iv) dose-dependently reduced systemic arterial blood pressure and mucosal blood flow, as determined by hydrogen gas clearance. Microscopic observation likewise indicated a dose-dependent slowing of mucosal capillary blood flow, as determined by red blood cell velocity after PAF infusion with stasis of flow at the highest dose. These actions were not the consequence of vasoconstriction, since there was no significant change in arteriolar and venular vessel diameter in the submucosa during PAF infusion, although a dose-related slowing and stasis of blood flow was observed. There was no capillary leakage of plasma protein in the gastric mucosa during PAF infusion, as determined by a fluorescence marker (FITC-BSA) technique. The precursor and breakdown product, lyso-PAF (200 ng X kg-1 X min-1) had no significant action on any of these microcirculatory parameters. These observations support the suggestion that microvascular changes leading to stasis may contribute to the ulcerogenic actions of PAF.

Effects of fluid-percussion brain injury on regional cerebral blood flow and pial arteriolar diameter.

The effects of two levels of fluid-percussion brain injury on cerebral blood flow (CBF) and pial arteriolar diameter were investigated in cats. Regional CBF was measured using the radioactive microsphere technique. Experimental brain injury resulted in changes in arterial blood pressure, CBF, and pial arteriolar diameter that were related to the severity of the injury. Low-level injury (1.88 +/- 0.11 atm, mean +/- standard error of the mean) resulted in a slight transient increase in CBF which had returned to preinjury levels by 30 minutes. High-level injury (2.68 +/- 0.19 atm) resulted in larger, statistically significant (p less than 0.01) increases in whole-brain CBF, decreases in cerebrovascular resistance, and increases in pial arteriolar diameter 1 minute postinjury. One hour after injury, CBF had returned to preinjury levels while cerebral perfusion pressure was significantly (p less than 0.01) reduced. There was no evidence of reduced CBF in any region studied. Pial arterioles dilated during the posttraumatic hypertensive period and then returned to control diameters within 1 hour after injury. Changes in the diameter of pial arterioles were significantly correlated with posttraumatic changes in CBF.

A microcirculatory technique for evaluating intravascular and topical administration of vasoactive agents: Response to AVP in the SHR

A “closed bath” cremaster muscle preparation is described which permits the administration of vasoactive materials to the microvasculature via intraarterial injection and topical suffusion. The technique is evaluated in spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats by comparing arteriolar responses to intraarterial and topically suffused arginine vasopressin. The preparation utilizes a thermostatically heated brass suffusion chamber overlying the cremaster. The chamber is closed with a glass coverslip. Experimental materials are presented to the microvessels via intraarterial injection or suffusion through the chamber. The coverglass permits high optical resolution with both routes of administration. Following vasopressin administration, changes in arteriolar diameter were continuously monitored by image-shearing techniques or variable-resistance calipers. The responses were analyzed by comparing both the peak 5-sec vasoconstriction and a 60-sec integrated response. Intraarterial and topical suffusion of vasopressin (1.25 × 10 −10–3.75 × 10 −7 M) caused dose-dependent vasoconstriction among 23-μm arterioles. Compared to the WKY, vasoconstriction was greater in the SHR when vasopressin was administered intraarterially. A similar strain difference was not observed with topical suffusion. The dose-response curves with intraarterial vasopressin were shifted approximately 100-fold in concentration to the right relative to those with topically suffused vasopressin. The “closed bath” cremaster muscle preparation described has several distinct advantages: (1) it permits introduction of different vasoactive materials in the most physiological manner in the same animal, and (2) it maintains high optical resolution and clarity for critical observation of the smallest vessels, even with suffusion.

Lidocaine constricts or dilates rat arterioles in a dose-dependent manner.

The microvascular effects of varying concentrations of lidocaine were evaluated with the use of videomicroscopy in an in vivo rat cremaster muscle preparation. Animals were anesthetized with chloralose and urethane and breathed room air spontaneously. Mean arterial pressure and heart rate were measured via a carotid artery cannula. The cremaster muscle was suffused with a balanced electrolyte solution and pH, temperature, PO2, PCO2, and osmolarity were controlled. Internal diameters of fourth-order arterioles in the cremaster muscle were measured with an electronic vernier system. In one group of animals (n = 7), arteriolar diameters were measured every 30 s during a 10-min control period, a 10-min period of topical application of lidocaine hydrochloride, and a 10-min recovery period. Lidocaine hydrochloride, 10(0), 10(1), 10(2), 10(3), or 10(4) micrograms X ml-1, produced changes in arteriolar diameters to 88.9 +/- 0.9, 79.0 +/- 1.3, 67.5 +/- 2.4, 60.1 +/- 3.4, and 127.1 +/- 7.2 per cent of control, respectively (P less than 0.001). In a second group of animals (n = 4), fourth-order arteriolar diameters were measured during administration of intravenous lidocaine, 1.2 mg X kg-1 bolus plus 0.3 mg X kg-1 X min-1. Vasoconstriction to 91.3 +/- 0.9% of control was observed (P less than 0.001). These results demonstrate a biphasic dose-dependent response to lidocaine. At lesser concentrations, including those that occur in the plasma of patients during intravenous infusion or nerve blocks, dose-related vasoconstriction occurred. Lidocaine, 10(4) micrograms X ml-1, a concentration similar to that which occurs at the site of injection during infiltration, nerve block, or epidural anesthesia, produced vasodilation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic sensitivity of different-size gastric submucosal arterioles

A gradation in the vasoconstriction response to norepinephrine has been reported in the rat mesentery, smaller arterioles being more sensitive than larger ones. The purpose of this investigation was to determine if this is also true of the rat gastric submucosal arterioles, the vessels which control gastric mucosal blood flow. The response of different-diameter gastric submucosal arterioles to the topical application of norepinephrine was studied. Arteriolar diameter changes were studied using in vivo microscopy with an image-splitting technique. Responses were expressed as percentage change from basal diameter. In response to topical norepinephrine all arterioles studied demonstrated constriction, escape, and poststimulation dilatation. The constriction responses of the precapillary arterioles (< 10 μ in diameter) and the larger arterioles (up to 79 μm) were of similar magnitude. The precapillary arterioles, however, dilated significantly more than larger ones in the post-stimulation period. These studies show that, unlike the rat mesentery, there is no gradation in sensitivity to norepinephrine constriction in the rat gastric submucosal arterioles.

Oxygen radicals mediate the cerebral arteriolar dilation from arachidonate and bradykinin in cats.

Topical application of sodium arachidonate (50-200 micrograms/ml) or bradykinin (0.1-10 micrograms/ml) on the brain surface of anesthetized cats caused dose-dependent cerebral arteriolar dilation. This dilation was blocked by 67-100% in the presence of superoxide dismutase and catalase. These enzymes did not affect the changes in arteriolar diameter caused by alterations in arterial blood PCO2, or the arteriolar dilation from topical acetylcholine. Enzymes inactivated by heat had no effect on the vasodilation from arachidonate or bradykinin. Superoxide dismutase alone or catalase alone reduced the dilation during application of 200 micrograms/ml of arachidonate for 15 minutes; they also completely prevented the residual dilation seen 1 hour after washout, as well as the reduction in the vasoconstrictive effects of arterial hypocapnia observed at this time. The results show that superoxide anion radical and hydrogen peroxide, or radicals derived from them, such as the hydroxyl radical, are mediators of the cerebral arteriolar dilation from sodium arachidonate or bradykinin. These radicals are not the endothelium-derived relaxant factor released by acetylcholine. The presence of both superoxide anion radical and hydrogen peroxide is required for the production of the vascular damage seen during prolonged application of high concentrations of sodium arachidonate.

Reduction of contraction-induced arteriolar vasodilation by adenosine deaminase or theophylline.

To test the hypothesis that adenosine mediates striated muscle blood flow, the cremaster muscle microcirculation was exposed to a continuous superfusion (10-30 min) of either a control, adenosine deaminase (7 micrograms protein/ml), or theophylline (10(-5) M) solution before, during, and following twitch contraction. Small arteriolar diameter and (dual-slit) blood flow velocity were continuously measured for 3 min before and after 2 min of electrical stimulation at 10, 5, or 2 Hz. Estimated arteriolar volume flow was calculated at 10-s intervals. The peak and average arteriolar diameter, peak and average estimated volume flow, duration of the exercise evoked response, and the total estimated volume of blood delivered in the 3-min postexercise period were reduced by deaminase as a function of stimulus frequency relative to a paired control. Deaminase reduced total estimated blood flow by 44, 35, and 22% at 10, 5, and 2 Hz, respectively. Although theophylline was more damaging to the tissue at a dose that was equieffective with deaminase, it produced a consistent reduction in peak and average arteriolar diameter and estimated volume flow after 5-Hz exercise. If changes in small arteriolar diameter are proportional to tissue blood flow changes, then these observations support the hypothesis that adenosine contributes to contraction-induced hyperemia in skeletal muscle in free-flow conditions and that its regulatory contribution depends on the intensity of the metabolic stimulus. Alternatively, these data could implicate adenosine in exercise-induced capillary recruitment.

Pial vessel caliber and cerebral blood flow during hemorrhage and hypercapnia in the rabbit.

We examined the relationship between cerebral blood flow (CBF) and pial vessel caliber responses to graded hemorrhagic hypotension at both normocapnia and hypercapnia in 31 anesthetized rabbits. Changes in CBF (hydrogen clearance) and pial arteriolar diameter (image splitting) were predictably related at all perfusion pressures (PP). Three autoregulatory regions were identified. 1) At PP greater than 65 mmHg, autoregulation was complete as CBF and the CBF response to hypercapnia remained at control levels. The pial vessels dilated progressively, and their response to hypercapnia increased. 2) At PP between 65 and 35 mmHg autoregulation continued but was incomplete. CBF decreased proportionately less than the corresponding reductions in PP due to continued pial vascular dilatation. Both the CBF and pial vessel responses to hypercapnia diminished. 3) At PP less than 35 mmHg, autoregulation was abolished. Pial arteriolar caliber and CBF decreased pressure passively, and there were no responses to hypercapnia. A comparison of changes in pial vascular resistance and total precapillary resistance indicated that the responses of pial vessels (particularly those less than 50 micron) paralleled the responses of the intraparenchymal arterioles.

Arteriolar responses to elevation of venous and arterial pressures in cat mesentery.

These studies were undertaken to determine the importance of metabolic (flow-dependent) and myogenic (pressure-dependent) factors in the response of arterioles to changes in intravascular pressure. The response of 26 arterioles in the isolated cat mesentery to increased venous and arterial pressure was studied by measuring changes of arteriolar diameter, red blood cell velocity, and intravascular pressure. Circumferential wall tension and volume flow in the arterioles were calculated. The fraction of the arteriolar responses to intravascular pressure elevation that could be attributed only to a myogenic response in which wall tension is regulated varied from 20 to 56%, depending on the method of pressure elevation. The largest fraction of the response attributable to a myogenic mechanism (ignoring the contributions of flow) varied from 50 to 93%. The fraction of the responses attributable only to flow dependency varied from 0 to 23%, whereas the largest fraction attributable to this mechanism varied from 18 to 73%, depending on the method of pressure elevation. It is concluded that, in cat mesentery, both metabolic and myogenic mechanisms appear to contribute to local regulation of flow with elevation of intravascular pressure, but other factors cannot be excluded.

The effects of thermal injury on rat skeletal muscle microcirculation.

An intravital microscopic study of rat skeletal muscle microvasculature was undertaken to assess changes in peripheral blood flow distant from thermal injury following burning. We found a significant increase in RBC velocity and quantitative flow in arterioles of animals with major thermal injury (28% TBSA full-thickness burn) compared to flow in animals with minor burns (18% TBSA) and control animals. There was no evidence for arteriolar diameter changes, erythrocyte sludging, or leukocyte-endothelial adherence. Major thermal injury is associated with an increase in skeletal muscle arteriolar blood flow distant from the site of injury.

Responses of single arterioles in vivo in cat skeletal muscle to change in arterial pressure applied at different rates.

The concept of a rate-dependent, dynamic as well as a static component in the myogenic control has been suggested in some previous in vitro and whole organ investigations. The present study is an attempt to reveal a dynamic component in the myogenic response directly on single arterioles by a vital microscopic technique. The study was made on the autonomically blocked vascular bed of cat tenuissimus muscle and performed by analysing the arteriolar diameter changes to an arterial pressure increase and decrease when applied at two different rates. The results demonstrate a transient, dynamic constrictor response upon the phasic increase in pressure and a transient, dynamic dilator response upon the phasic decrease in pressure, the magnitudes of which being related to the rate of the pressure change. The static response developing during the steady-state phase of constant increased pressure was also shown. The dynamic responses were confined to arterioles smaller than about 20 micrometers while the steady-state response was present in larger arterioles as well. Even if the metabolic control system partly could be responsible for the obtained responses, arguments are given that the described reactions are mainly myogenic in nature.

Acute effects of salbutamol on arteriolar vasodilatation and blood pressure in spontaneously hypertensive rats

The acute effects of salbutamol, a β 2 agonist, on arteriolar vasodilatation and blood pressure were studied in WKY and SHR rats. The cremaster muscle was prepared for in vivo microscopy and the femoral artery cannulated for administration of salbutamol (0.001- to 4.0-μg doses). Systemic mean arterial pressures were measured from the carotid artery. Changes in arteriolar diameter were recorded on videotape and analyzed using variable resistance calipers to trace the changes in diameter. In both WKYs and SHRs salbutamol induced dose-dependent vasodilatations, the magnitudes of which were inversely related to the resting diameter. Among arterioles 35 μm or less in diameter, the SHRs exhibited significantly greater percentage vasodilatations. Vasodilatation among arterioles greater than 35 μm was strongly attenuated at all doses in both WKYs and SHRs. These vasodilatory responses were accompanied by dose-dependent decreases in the mean arterial pressure. At all doses the absolute pressure drop was greater in the SHR, although the percentage decreases were similar. Both the vasodilatations and blood pressure decreases were blocked by propranolol. This enhanced vasodilatory capacity to β 2 stimulation by the smaller SHR arterioles may serve as part of a compensatory mechanism to maintain sufficient blood flow regulation in the face of a reduced vascular density.

Responses of pulmonary allograft and cheek pouch arterioles in the hamster to alterations in extravascular pressure in different oxygen environments.

The responses to changes in transmural pressure were investigated in pulmonary allograft and cheek pouch arterioles in two oxygen environments. Neonatal hamster lung tissue was transplanted into adult hamster cheek pouches. After vascularization (8-10 days), pulmonary and cheek pouch vessels were observed by intravital microscopy in hamsters anesthetized with pentobarbital. By gassing the suffusion solution (bicarbonate-buffered Ringer's) (pH 7.4 at 35-37 degrees C) with either low oxygen (95% N2/5% CO2) or high oxygen (75% N2/5% CO2/20% O2) and after sealing the top of the chamber, extravascular pressure was altered by varying the fluid volume of the closed chamber. Changes in arteriolar diameters in response to positive and negative square-wave pressure pulses were quantified using a video micrometer and close-circuit TV system. Pulmonary arterioles showed a passive dilation or constriction in response to increases or decreases in transmural pressure (+/-20 mm Hg). These responses were not altered either by changes in PO2 or nitroprusside. In contrast, cheek pouch arterioles showed myogenic responses by constricting when transmural pressure was increased and vice versa. These responses were potentiated at high PO2 and abolished with nitroprusside. It is concluded that a myogenic response is dominant in cheek pouch arterioles but not in pulmonary arterioles under these conditions. These latter observations are consistent with results obtained from isolated, intact lung.

Direct evidence for myogenic autoregulation of the renal microcirculation in the hamster.

We transplanted neonatal hamster renal tissue into a hamster check pouch chamber and subjected the renal tissue to increases and decreases in extravascular pressure. A decrease in extra-vascular pressure decreased, and an increase in extravascular pressure increased, the diameter of preglomerular arterioles. Thus, the change in preglomerular arteriolar diameter was directly related to alterations in extravascular pressure. Neither saralasin nor indomethacin affected these changes, whereas papaverin prevented them. The efferen arterioles responded passively to changes in extravascular pressure; i.e., the changes in their diameter were inversely related to changes in extravascular myogenic autoregulation of preglomerular vessels.

Histamine receptors in the gastric microcirculation.

The types and functions of histamine receptors in the submucosal arterioles of the corpus and antrum of the cat and rat stomach were studied using an in vivo microscopy technique. Change in arteriolar diameter in response to superfusion of histamine with and without antagonists was measured by an image-splitting technique. H1 and H2 histamine receptors subserving vasodilatation were demonstrated in both the antral and corpus submucosal arterioles of the cat and rat. However, the H1 effect was predominant in the antrum (the H2 antagonist inhibited histamine dilatation only in the presence of the H1 antagonist), while H1 and H2 effects were approximately equal and independent in the corpus.

Role of oxygen in arteriolar functional vasodilation in hamster striated muscle.

Small isolated groups of striated muscle cells were stimulated in the hamster cremaster muscle. During and after stimulation, oxygen microelectrodes were employed to determine the relationships among arteriolar vasodilation, tissue Po2, and periarteriolar Po2. Localized contraction produced a biphasic arteriolar vasodilation without associated alteration of Po2 on the surface of the arterioles (vascular smooth muscle Po2). In contrast, muscle contraction produced a decline in muscle tissue Po2 that was proportional to the contraction frequency over the range of 1--4 contractions per second. An increase in contraction frequency also produced a graded increase in arteriolar diameter, the magnitude of which was statistically correlated with the steady-state change in tissue Po2. However, arteriolar diameter changes preceded tissue Po2 changes, both with the initiation of functional dilation and during the recovery period. Tissue Po2 was manipulated at rest and during contraction by increasing the Po2 of the superfusion solution. Increasing the tissue Po2 caused a decrease in vascular diameter under both conditions and a reduction in the magnitude of the arteriolar vasodilation during contraction. Restoration of tissue Po2 to resting levels during muscle contraction produced only partial restoration of vascular diameters. The results are consistent with the hypothesis that at least three components are involved in the vascular control process during muscular activity: an early component independent of tissue oxygen levels, a late component independent of oxygen, and a late component associated with a decrease in muscle Po2, without an effect on vascular smooth muscle Po2. The evidence indicated that Po2 of the smooth muscle of the arterioles had no role in the dilation observed.

The sausage-string phenomenon in acutely induced hypertension--arguments against the vasospasm theory in the pathogenesis of acute hypertensive encephalopathy.

Pial microcirculation was observed in cats during acutely induced blood pressure increase using the window technique. Measurements of arteriolar diameter changes in situations of preserved and altered cerebrovascular autoregulation were made, when diffuse vasoconstriction and sausage-like dilation, respectively, occurred. Comparison of percentage changes of narrow segments between sausage-like dilated arterioles and diffusely constricted (= autoregulating) vessels gave evidence that a failure of autoregulation in this situation is not associated with vasospasm but with dilation. Individual narrow segments did not constrict more--but on an average even rather less--than diffusely constricted vessels. Evans blue extravasation occurred only with dilation, never with vascular constriction. From these data it is concluded that extravasation due to acute blood pressure increase is not of ischemic nature, but a consequence of high filtration pressure due to arteriolar and venous congestion.

Brain microvascular hemodynamic responses to induced seizures.

Arteriolar diameters and venular erythrocyte velocities in the small pial vessels on the surface of the cat brain were measured by TV methods during induced epileptic seizures through a cranial window. Grand mal seizures maximally dilated arterioles and increased venular erythrocyte velocity up to 400%. High positive correlation existed between changes in CSF hydrogen ion concentration and pial arteriolar diameter, suggesting metabolic regulation of CBF through CSF/interstitial fluid hydrogen ion alterations during the seizure.

Inhibition of bradykinin vasodilation and potentiation of norepinephrine and angiotensin vasoconstriction by inhibitors of prostaglandin synthesis in skeletal muscle of the rat.

Recent reports have indicated that vascular responsiveness can be altered by exogenously administered or endogenously released prostaglandins. Furthermore, in certain tissues inhibitors of prostaglandin synthesis have been shown to limit the increase in blood flow in response to bradykinin and to enhance the reduction in blood flow in response to angiotensin and norepinephrine. These findings suggest an important local circulatory role for prostaglandins. We attempted to implicate further prostaglandins in local blood flow regulation by examining the effects of indomethacin (IND) and 5,8,11,14-eicosatetraynoic acid (ETA), inhibitors of prostaglandin synthesis, on microvascular arteriolar responses to bradykinin, prostaglandin E1 (PGE1), prostaglandin E2 (PGE2), histamine, norepinephrine, and angiotensin. Male Wistar rats were anesthetized with sodium pentobarbital, and their cremaster muscle was exteriorized and prepared for in vivo microscopic observation of microvessels. Changes in arteriolar luminal diameters in response to topical administration of vasoactive agents were quantified with an image-shearing measuring eyepiece in conjunction with a television microscope and recorder. Local administration of IND or ETA significantly reduced the arteriolar dilation elicited by bradykinin, whereas the responses to PGE1 and PGE2 remained unaltered. Responses to histamine, although somewhat reduced, were not significantly different from control. Vasoconstrictor responses of arterioles elicited by norepinephrine and angiotensin were potentiated by IND or ETA administration. These results indicate that prostaglandins synthetized in skeletal muscle microcirculation in situ (1) mediate, in part, vasodilator responses to bradykinin and (2) modulate vasoconstrictor responses to angiotensin and norepinephrine. Thus, these findings support the hypothesis that prostaglandins are local regulators of microvascular responsiveness.