An explanation of the "supernormal" b-wave in vitro.

The isolated arterially perfused eye preparation has proven to be comparable to the in vivo model in many respects. However, the existence of "supernormal" b-wave amplitudes in the perfused eyes has remained an unexplained functional difference between the two preparations. The term "supernormal" reflected the observation that at high perfusate flow rates the amplitude of the b-wave from the perfused eyes was frequently larger than that recorded in vivo under the same stimulus and adaptation conditions. Recent investigations in this laboratory have demonstrated that the position of the scleral electrode on the isolated eye greatly influences the amplitude of the b-wave obtained. The simple comparison of b-wave amplitudes in vivo and in vitro was therefore not appropriate, due to the different electrode locations used in the two situations. In addition, the relationship between perfusate flow rate and b-wave amplitude at a fixed location has been reinvestigated. In our perfusion system the b-wave amplitude has been shown to saturate at moderate flow rates (1.5 ml/min), considerably lower than those required to maximize the b-wave amplitude in earlier studies. This difference is due to the higher oxygen tension of our perfusate at the entry point to the eye. It is concluded that b-wave stability with increasing perfusate flow can be achieved in vitro, and that the apparently supernormal b-wave amplitudes observed under these conditions can be explained in terms of the different electrode environment in the in vivo and in vitro preparations. The implications of these findings with regard to autoregulation of the retinal circulation are discussed.

Effect of hypoxia on the maintained firing rate of retinal ganglion cells.

The effect of systemic hypoxia on the maintained firing rate (MFR) of single retinal ganglion cells has been measured in the cat at a constant luminance level. Systemic hypoxia was produced by reducing the percentage of oxygen in the respiratory mixture under forced ventilation so that arterial PCO2 and pH were constant. Extracellular recordings were obtained from both X and Y retinal ganglion cells before, during, and after systemic hypoxia, with each cell acting as its own control. The MFR was unaltered by arterial PO2 levels of greater than 45 mm Hg. However, at and below this level of hypoxia the MFR was reversibly increased in 67% of the cells tested. Whether or not this increase occurred was independent of cell type or location. For arterial PO2 values of 24 to 34 mm Hg the initial increase in MFR was followed by a decrease for these cells; for PO2 values of less than 24 mm Hg the MFR showed a large initial increase followed by a complete cessation of firing. The remaining 33% of cells displayed only reduced MFR during hypoxia. The results indicate that ganglion cell function may be drastically affected by hypoxia. This may be relevant to the visual loss of a variety of retinal disorders.

The effect of regional retinal photocoagulation on vitreal oxygen tension.

PO2 measurements have been made for the first time within the retina and vitreous of cat eyes to compare normal and photocoagulated areas. This was done to test the hypothesis that the observed beneficial effects of pan-retinal photocoagulation therapy in the treatment of retinal vascular diseases with an ischemic origin, may be due to more oxygen becoming available to the remaining functioning retina. A xenon arc photocoagulator was used to photocoagulate large areas of cat retinas served by one major set of vessels while leaving the remaining retina untouched. After 6 months an acute experiment was performed in which retinal and vitreal oxygen tension profiles were measured using oxygen-sensitive microelectrodes to compare PO2 profiles in normal and photocoagulated regions, for two ventilation conditions: air and 100% O2. The only differences in PO2 values were found for the 100% O2 breathing condition, where values within the retina and in the overlying vitreous were larger in photocoagulated areas. It is proposed that any differences in PO2 distribution which occur for air breathing are masked by the autoregulatory capacity of the retinal circulation and the PO2 buffering capacity of hemoglobin.

The retinal oxygen profile in cats.

This study records for the first time the retinal tissue oxygen partial pressure as a function of location within the retina of the domestic cat. Tissue pO2 was recorded with oxygen sensitive microelectrodes that use the polarographic principle. The mean vitreal pO2 close to the internal limiting membrane was 20.2 +/- 2.3 mmHg. The internal limiting membrane does not act as a diffusion barrier for oxygen. As the electrode was advanced into the inner retina, the tissue pO2 rose gradually to a value of 24.6 +/- 2.3 mmHg and then fell to a minimum of 12.0 +/- 5.5 mmHg before rising again to a value of 29.2 +/- 2.5 mmHg. Further insertion resulted in a sudden steep rise of tissue pO2 values to 72.0 +/- 5.1 mmHg, after which there was no further alteration in measured values. Although the exact location within the retina of the recording electrode was not known, it is probable that the tissue pO2 minimum occurs at about the level of the inner nuclear layer. Therefore, it is probable that the retinal avascular layers receive their oxygen supply primarily from the choroidal circulation in the cat.

PO2 profiles and oxygen consumption in cat retina with an occluded retinal circulation.

If the retinal circulation is occluded, the retina is forced to rely on the choroidal circulation for its oxygen supply. We have measured intraretinal PO2 profiles before, during, and after such an occlusion in cat. Oxygen-sensitive microelectrodes were used to measure intraretinal PO2, and the retinal circulation was occluded by means of a glass probe placed on the retinal vessels at the optic disk. Both air and 100% O2 breathing conditions were investigated. With the retinal circulation occluded, intra-retinal PO2 fell to zero within 60% of the distance through the retina, measured from the choriocapillaris to the internal limiting membrane. With the circulation occluded, but with breathing of 100% O2, PO2 rose throughout the retina so that values within the inner retina were as high or higher than for air breathing with the retinal circulation present. This meant that the whole retina could be supplied with adequate oxygen by breathing with 100% O2 in cat. From these PO2 profiles, oxygen flux and consumption were calculated as a function of distance through the retina. These calculations showed that the outer 20% of the retina had a consumption of 5.45 +/- 2.46 (SD) ml.min-1.100 ml-1 compared with a mean value for the remaining retina of 1.47 +/- 2.66 ml.min-1.100 ml-1. This difference was statistically significant (P less than 0.001) which indicates that there are at least two regions in the retina with different oxygen consumption.

The response of rat vitreal oxygen tension to stepwise increases in inspired percentage oxygen.

The effect of graded systemic hyperoxia on vitreal PO2 distribution has been determined for the rat eye. Oxygen tension profiles were measured, using oxygen-sensitive microelectrodes, as a function of distance from the internal limiting membrane as the inspired oxygen percentage was increased in 10% steps from 20-100%. Depending on the original touching location of the microelectrode on the retina, there could be substantial PO2 gradients within 500 microns of the retina; at greater distances vitreal PO2 was constant and a function of the inspired oxygen percentage. Whatever the location of the microelectrode in the vitreous, PO2 rose with increasing hyperoxia. The relationship between vitreal PO2 and inspired oxygen was nonlinear with a central relatively flat region between 50-80% inspired oxygen. The ratio between vitreal PO2 during 100% O2 breathing and air breathing was 3.42 +/- 1.08 (standard deviation, n = 7). Possible explanations for the plateau region are the maintenance of a relatively constant PO2 by vascular autoregulation and/or the buffering of capillary PO2 by hemoglobin. The rat eye, therefore, responds to hyperoxia similarly to that of the cat and monkey but differs from that of the miniature pig where there is no rise in preretinal PO2 during hyperoxia.

A new method for oxygen supply to acute ischemic retina.

This paper introduces a new method for supplying oxygen directly to ischemic inner retina, using an oxygen source in the vitreous. Acute retinal vascular occlusion was created in cat eyes by direct pressure on the optic disk and its margins with a glass probe. The satisfactory occlusion of the retinal vessels was documented by direct observation, and functionally by recording the ERG. The vascular occlusion caused a large decrease in the size of the ERG b wave, with no change in the a wave amplitude. The oxygen source was a catheter made of strands of an oxygen-permeable membrane which was inserted into the vitreal cavity. After successful vascular occlusion was documented, 100% gaseous oxygen was perfused through the catheter while recording the ERG. In response to the perfused oxygen the b wave partially recovered. Ventilating the animal with 100% oxygen when the retinal vessels were occluded also caused recovery of the b wave amplitude. Termination of the vitreal oxygen source caused a decrease in b wave amplitude to the level previously observed after the occlusion of the retinal vessels. When the retinal circulation was restored by removal of the glass probe the b wave recovered. The results show that it is possible to supply adequate oxygen to the inner retina via the vitreous to replace the oxygen normally supplied by the retinal circulation. Modification of this method may be useful for the treatment of recent and incomplete retinal vascular occlusion.

Direct vasodilatory effect of insulin on isolated retinal arterioles.

PURPOSE: To test the hypothesis that insulin has a direct vasodilatory effect on retinal arteries and their branches and to investigate the mechanisms involved. METHODS: Segments of porcine retinal arteries were dissected, cannulated, and perfused. Vessel diameter was measured continuously on-line. Vessels were precontracted to 66% +/- 0.9% (SEM, n = 148) of their original diameter by perfusing with 124 mM K(+)-Krebs solution. Dose-response curves to insulin (2 to 2000 microU/ml) were compared for extraluminal (EL), intraluminal (IL), and combined IL-EL application. The effect of cyclooxygenase and nitric oxide synthase inhibition on the insulin response was determined, as was Ca2+ channel involvement. RESULTS: EL insulin alone had no significant effect on vessel diameter. IL insulin produced a dose-dependent dilatation of 5.6% +/- 2.9% (n = 22) of the K+ contracted diameter at 200 microU/ml and up to 12.4% +/- 3.6% (n = 22) by 2000 microU/ml, whereas combined IL-EL insulin application caused dilatation at all concentrations, rising to 15.1% +/- 2.9% (n = 44) at 200 microU/ml and 19.7% +/- 3% (n = 44) at 2000 microU/ml. IL indomethacin (5 x 10(-5) M) had no significant effect on the insulin-induced dilatation, whereas IL L-NAME (10(-4) M) inhibited insulin dilatation completely. The addition of EL verapamil (10(-6) M) during insulin-induced dilatation resulted in further dilatation to 37.8% +/- 4.2% (n = 18). However, the addition of insulin to verapamil-dilated vessels caused no further dilatation. Exposure to EL insulin while the IL K+ contraction dose-response curve was measured had no effect. Results in main arteries and branches did not differ. CONCLUSIONS: The IL application of insulin dilates potassium-contracted pig retinal arteries. This effect was enhanced by the EL presence of insulin, which did not result in dilatation when it was administered alone. The dilatation response was mediated by nitric oxide but not by prostaglandins. There was some evidence for the involvement of Ca2+ channels in insulin-induced dilatation. These results imply that insulin is a vascular regulator in normal conditions and may have relevance to the vascular changes occurring in diabetes and hypertension in the retina.

Effects of extracellular pH on agonist-induced vascular tone of the cat ophthalmociliary artery.

PURPOSE: To test whether changes in extracellular pH (pHe) in an in vitro preparation of the cat ophthalmociliary artery affect passive tone and agonist responses and whether the endothelial cells are mediators of any pH-induced effect. This will determine the ability of the ophthalmociliary artery to influence retinal and choroidal blood flow in response to metabolic stimuli. METHODS: The isometric tension generated by isolated ring segments preactivated by prostaglandin F2 alpha (PGF2 alpha), noradrenaline (NA), or 40 mM K+ was measured as the pHe of the bathing solution was changed stepwise from 6.0 to 8.0 by adjusting the bathing bicarbonate concentration in preparations with and without functioning endothelial cells. RESULTS: PGF2 alpha produces a concentration-dependent contraction that is insensitive to an alkaline shift from control pHe (7.4) in the bathing medium. For acidic shifts to pHe 7.0, there is no significant change in the magnitude of the PGF2 alpha contraction, whereas at pHe 6.0, the PGF2 alpha contraction is reduced to 23 +/- 4% (n = 23) of its value at pHe 7.4. Threshold response concentration remains unaffected. Deliberate damage to the endothelial cells does not significantly affect the magnitude of the 10(-5) M PGF2 alpha response at pHe 7.4 nor the effect of acidic pH on this response. The 10(-5) M NA response is reduced in a graded fashion to acidic shifts to pH 7.0 and 6.0 (40 +/- 4% [n = 23]) and also to alkaline shift to pH 8.0 (22 +/- 5% [n = 23]) when compared to the induced tension at pHe 7.4. For the acidic shift only, endothelial cell damage causes a further significant reduction in the NA response to 20 +/- 3% (n = 5). For vessels contracted with K(+)-Krebs solution, there is a small but significant reduction in response at pHe 6.0 to 84 +/- 6% (n = 25), whereas for pHe 8.0 there is a much larger reduction to 45 +/- 5% (n = 24). All pHe-induced relaxations of K+ are endothelium independent. Passive tension is unaffected by all pHe manipulations. CONCLUSIONS: Vessel responses to vasoactive agents are selectively mediated by pHe changes. Major acidic shifts cause reduced responses (relaxation) to NA, PGF2 alpha, or K+, whereas only vessels preactivated with NA and K+ relax to alkaline shifts. This implies that NA or K+ induced vascular responses are maximal close to neutral pHe with major shifts from neutrality in either the acidic or alkaline direction causing a reduced response. These results imply that the ophthalmociliary artery probably does not play a major role in controlling ocular blood flow in response to pHe changes within the normal metabolic range, but it may become important in ischemic conditions.

Vasoactivity of intraluminal and extraluminal agonists in perfused retinal arteries.

PURPOSE: To evaluate the vasoactive response of isolated perfused arteries of the pig to K+ and adrenergic agonists and to compare the effects of intraluminal (IL) and extraluminal (EL) drug delivery. METHODS: A new microperfusion system was developed, in which short lengths of porcine retinal arteries (outer diameter 90.4 +/- 2.7 microns) were cannulated at both ends and perfused at a controlled rate (5 microliters/min) with outflow through a single side branch. The diameter of the vessel and the intraluminal pressure were monitored, and the effect of intraluminally and extraluminally applied agonists was determined. Endothelial cell function and the integrity of the blood retinal barrier was verified. RESULTS: Consistent vasoactive responses were obtained from most vessels. The resting diameter of the vessel was not greatly influenced by changes in flow rate or intraluminal pressure over the physiological range. Adrenaline and noradrenaline caused dose-dependent contractions, which were larger when applied intraluminally than they were when applied extraluminally. The largest contraction for adrenaline was 19.0% +/- 2.1% (n = 13) IL and 8.4% +/- 1.5% (n = 13) EL, and for noradrenaline, 17.8% +/- 1.9% (n = 13) IL and 6.8% +/- 1.1% (n = 13) EL. The IL contraction to 124-mM K+, 19.0% +/- 1.6% (n = 21), was also greater than that for EL application, 5.0% +/- 1.0% (n = 13). We found that the existence of myogenic contractions was restricted to the special case in which vessels with no branches were pressurized under zero flow conditions. CONCLUSIONS: Pig retinal arteries exhibited asymmetry in their responses to adrenergic agonists and K+, with contractions significantly larger when the drug was applied to the intraluminal surface rather than the extraluminal surface. This asymmetry may reflect an important property of retinal vessels. Microperfusion systems of this type may prove valuable in developing a better understanding of control mechanisms in retinal circulations.

The patency of the retinal vasculature to erythrocytes in retinal vascular disease.

This paper presents the first evidence that in retinas with experimentally induced vascular disease some vessels contain only plasma. This was demonstrated by a histologic technique developed specifically to test the hypothesis that at some stage in retinal vascular disease, vessel patency to erythrocytes is lost before vessels close to plasma. Using this technique, we visualized three major components of the circulation at all retinal locations: the erythrocytes; the plasma as marked by the presence of 0.2-micron fluorescent microspheres; and all functioning endothelial cell nuclei, which were marked by the fluorochrome bis-Benzimide. It was assumed that the distributions of the erythrocytes and small particles in retinal whole mounts reflected accurately the true in vivo distributions at the moment of circulation arrest. Postenucleation the retina can be viewed and photographed within 45 min of circulation arrest. The technique was used on normal rats and on rats induced with a fast-developing model of retinal vasculopathy. With this model, we demonstrated retinal vascular segments perfused by plasma but containing no erythrocytes with functioning endothelial cells in the vessel walls. This may mean that an early factor in some retinal vascular pathologies is tissue hypoxia caused by reduced erythrocyte perfusion.

Oxygen reactivity of the feline isolated ophthalmociliary artery.

PURPOSE: The goal of this study was to investigate the modulating role of oxygen tension on noradrenaline (NA) and KCl responses in the ophthalmociliary artery and to ascertain whether these effects are mediated by the endothelial cells. METHODS: The isometric tension generated by myograph ring segments activated by NA or KCl was measured as the PO2 of the bathing solution was decreased in discrete steps from 506.1 +/- 16.0 mmHg to 29.4 +/- 1.4 mmHg in preparations with and without endothelial cells. RESULTS: Vessels pre-activated with K+ Krebs solution were insensitive to oxygen tensions between 506.1 +/- 16.0 mmHg and 124.6 +/- 4.2 mmHg. Lower PO2s caused a graded and increasing contraction that reached 176 +/- 12% of the contraction at the highest PO2. Vessels pre-activated with NA had a dichotomous response to reductions in oxygen tension: 44% of vessels showed a graded contraction, whereas a graded relaxation was observed for the remaining 56% of vessels as bath PO2 was reduced. In all cases, a functional endothelium was demonstrated. However, deliberate disruption of the endothelium caused all vessels pre-activated with NA to exhibit a consistent graded contraction for PO2s below 124.6 +/- 4.2 mmHg, similar to that observed for endothelial intact vessels pre-activated with K+ Krebs. The acetylcholine dose-response curve and passive tension were not affected by changes in oxygen tension. CONCLUSIONS: Endothelial cells modify the intrinsic smooth muscle response to a gradual reduction in PO2 by releasing relaxing and contracting factors, causing the observed dichotomous response in NA-activated vessels. However, the KCl-induced response is modulated only by low oxygen tensions.

Retinal blood flow by hydrogen clearance polarography in the streptozotocin-induced diabetic rat.

PURPOSE: The authors compared retinal blood flow in rats after 5 weeks of streptozotocin (STZ)-induced diabetes with that in age-matched control animals. METHODS: The flow measurements were based on the hydrogen clearance technique and the intraocular placement microelectrodes at the surface of the retina. The hydrogen was delivered by bolus injection (100 microliters) of hydrogen-saturated saline into the ipsilateral carotid artery using a cannula through the lingual artery. The rats were anesthetized and artificially ventilated. Care was taken to match the systemic blood pressure and blood gases in the two groups. RESULTS: The mean retinal blood flow in the STZ group after 5-6 weeks duration of hyperglycemia was 487 +/- 59 ml/min/100g (standard error) compared with 330 +/- 16 ml/min/100 g in the age-matched controls. The variation in retinal blood flow was far more pronounced in the STZ group, even in different locations in the same eye. Changes in fundus appearance were also noted, with second-order arterioles being more apparent and the retina more "pinkish" in appearance in the STZ animals. CONCLUSIONS: The mean retinal blood flow in the region of retina studied in the two groups was significantly higher in the STZ animals than in age-matched controls. The increased heterogeneity of retinal blood flow may reflect a disruption to the normal blood flow control mechanisms in the retina after only 5 weeks of STZ-induced diabetes.

Agonist response of human isolated posterior ciliary artery.

The isometric responses of isolated human posterior ciliary artery to adrenergic agonists, histamine (HIS), and 5-hydroxytryptamine (5-HT) were studied in passively stretched ring segments mounted in a myograph bath. Cumulative dose response curves were measured for nine agonists: HIS, 5-HT, dopamine (DOPA), epinephrine (A), norepinephrine (NA), tyramine (TYR), phenylephrine (PHE), isoproterenol (ISOP), and xylazine (XYL), and the log(molar concentration) at which one half of the maximum active tension was developed (EC50) was estimated. The ring segments were unresponsive to DOPA and XYL; HIS and ISOP produced biphasic responses with a mild relaxation for low concentrations and small contractions for high concentrations of the agonist. The remaining agonists caused contractile responses of magnitude listed in the rank order following compared with the maximum active tension in response to 0.124 M K(+)-Krebs: Kmax much greater than A greater than 5-HT = PHE greater than NA greater than TYR It was concluded that functional HIS, alpha 1-adrenergic, and 5-HT receptors were present on human posterior ciliary artery but that there are no alpha 2-adrenergic receptors.

The influence of cerebrospinal fluid pressure on the lamina cribrosa tissue pressure gradient.

PURPOSE: To measure the tissue pressure gradient through the optic disk and to determine the relationship between intraocular, cerebrospinal fluid, and retrolaminar tissue pressures. The relationship of optic nerve subarachnoid space pressure to intracranial cerebrospinal fluid pressure also was explored. METHODS: Micropipettes coupled to a pressure transducer were passed through pars plana and vitreous to enter the optic disk in the anesthetized dog. Using a micromanipulator, pipettes penetrated the optic disk in steps while pressure measurements were taken. In some animals, pipettes also were passed into the optic nerve subarachnoid space. Lateral ventricle cerebrospinal fluid pressure, intraocular pressure, and arterial blood pressure were measured concurrently, and the effect of raising CSF pressure was explored. RESULTS: Retrolaminar tissue pressure was largely dependent on the surrounding cerebrospinal fluid pressure, which was on average 8.6 +/- 3.5 mm Hg (SD, n = 8) higher, and was independent of intraocular pressure. Most (85% +/- 15% [SD, n = 8]) of the pressure drop between intraocular pressure and retrolaminar pressure occurred across the anterior 400 microns of disk tissue. When the intraocular pressure was 21 mm Hg and the cerebrospinal fluid pressure was zero, retrolaminar tissue pressure averaged 7 mm Hg and the translaminar pressure gradient was 3.08 +/- 0.29 mm Hg/100 microns tissue (SD, n = 3). Optic nerve subarachnoid space pressure was equivalent to lateral ventricular pressure. CONCLUSIONS: These results show that cerebrospinal fluid pressure largely determines retrolaminar tissue pressure; hence, along with intraocular pressure, it is of major importance in setting the translaminar tissue pressure gradient. Results also demonstrate hydrostatic continuity between the optic nerve subarachnoid space and the lateral ventricle. That the translaminar pressure gradient can vary independently of intraocular pressure may be of importance in understanding the pathophysiology of glaucoma.

The correlation between cerebrospinal fluid pressure and retrolaminar tissue pressure.

PURPOSE: To measure the effects of cerebrospinal fluid pressure (CSFp) on retrolaminar tissue pressure (RLTp) and the translaminar pressure gradient (TLPG), particularly at low CSFp, which is the normal situation in erect posture. METHODS: Micropipettes coupled to a servonull pressure system were passed into eyes of anesthetized dogs to the optic disc and advanced in steps through the lamina cribrosa to the optic nerve subarachnoid space (ONSAS), while pressure measurements were taken. Cerebrospinal fluid pressure and intraocular pressure (IOP) were monitored and controlled. The TLPG was measured at varying IOPs and CSFps. The RLTp and ONSAS pressure (ONSASp) were measured at varying CSFps. In separate experiments, the optic nerve dura was incised, and pressure measurements were taken across the pia mater. RESULTS: The TLPG was strongly correlated to the difference between IOP and CSFp (r=0.93; n=18) when CSFp was more than zero. Mean RLTp was 3.7+/-0.2 mm Hg (SEM; n=15) when CSFp was 0 mm Hg. The ONSASp and RLTp were largely dependent on the presence of CSFp higher than break point pressures of -0.5 mm Hg and 1.33 mm Hg, respectively. However, below these break points, RLTp (slope 0.07) and ONSASp (slope 0.18) were little influenced by CSFp. Separate measurements across the pia mater revealed that 95% of the pressure drop occurred within 100 microm of the pial surface. CONCLUSIONS: The TLPG and RLTp are dependent on CSFp when CSFp is more than -0.5 mm Hg. Below this level, there is no hydrostatic continuity between the intracranial and optic nerve subarachnoid space. In this range, RLTp is stable and is little influenced by CSFp changes.

Systemic and ocular vascular roles of the antiglaucoma agents beta-adrenergic antagonists and Ca2+ entry blockers.

This review addresses whether the antiglaucoma agents beta-adrenergic antagonists and Ca2+ entry blockers cause vasoactive effects in the retinal and other ocular vasculatures, as they do in other tissues. The potent vasodilating effects of Ca2+ entry blockers on ocular vessels have recently been demonstrated in in vivo and in vitro studies, implying that the maintenance of ocular vascular tone relies almost exclusively on extracellular Ca2+. Ca2+ entry blockers may potentially play a role in relaxing the retinal, long posterior ciliary, and ophthalmociliary arteries to improve the ocular circulation in vascular diseases in which there is considerable vascular tone present. The beta-adrenergic antagonists are discussed with reference to their antihypertensive role, their effect on other vascular beds, and finally what is known of their effect in the ocular vasculature. The emerging evidence that particular selective beta-adrenergic antagonists, such as betaxolol, are also potent Ca2+ channel entry blockers in other vascular beds is presented. Betaxolol has been shown to induce vasodilatation in the retinal and other ocular vascular beds, although studies have shown that beta1-adrenergic receptors are sparse in these vascular beds. This implies that an alternative mechanism must be responsible for betaxolol-induced vasodilatation. Evidence is presented that betaxolol vasodilates via its potent Ca2+ channel entry blocking properties, and its potency and ability to vasodilate are compared with those of nimodipine and timolol, as well as with those of other Ca2+ channel entry blockers. Important areas for future research in this area are discussed.

Acetylcholine-induced vasodilation of isolated pulpal arterioles.

The presence of cholinergic mechanisms in the control of pulpal microcirculation has been a controversial issue. In this study, we aimed to determine the direct vasoactive responses of isolated pulpal arterioles to acetylcholine, and to investigate whether such responses are endothelium-dependent. Using an in vitro micro-perfusion system, we isolated pig pulpal arterioles, cannulated and perfused them intraluminally, and monitored the diameter. Following equilibration, the vessels were contracted with 10(-5) M noradrenaline, and the effect of increasing doses of acetylcholine was determined. The influence of the muscarinic antagonist, atropine, or the loss of endothelial cell function following saponin treatment was also determined. Acetylcholine induced a dose-dependent vasodilation, reaching 94.6+/-1.4% (n = 22) of the uncontracted diameter at 10(-4) M. The vascular relaxation effect of acetylcholine was abolished in the presence of atropine, and by saponin treatment. Analysis of these data suggests that, in the pig, the acetylcholine-induced vasodilation of incisor pulpal arterioles is endothelium-dependent and mediated by muscarinic receptors.

Relation between pressure determined by ophthalmodynamometry and aortic pressure in the dog.

AIMS: Ophthalmodynamometry has been used extensively since the last century; however, controversy surrounds what it actually measures. This study was set up to determine the relation between ophthalmodynamometric (ODP) and systemic blood pressures. METHODS: Aortic pressure was continuously monitored and altered by phlebotomy in six anaesthetised dogs, while ophthalmodynamometry was performed, by directly altering intraocular pressure. Maxillary artery pressure was monitored in two animals. All pressure transducers were zeroed at eye level. RESULTS: Mean ODP was 96.6% (1.6%) (95% confidence interval, n = 49) of aortic pressure. Mean maxillary artery pressure was 95.7% (5.5%) (95% CI, n = 16) of aortic pressure. ODP was 1.9 (0.6) mm Hg (95% CI, n = 33) higher than maxillary artery pressures. CONCLUSION: ODP was only slightly below aortic pressure and not significantly different from maxillary artery pressure, the analogue of the internal carotid artery in humans. These results also suggest a retinal artery collapse pressure of at least 1.9 mm Hg.

Image splitting--a technique for measuring retinal vascular reactivity.

The observation of changes of pial vessel calibre has withstood the test of time in assessing cerebrovascular reactivity. A recent refinement has been the adoption of the image splitting television technique of Baez, which allows accurate and rapid measurements of vessel calibre to be made in situ. This method has been successfully applied to the eye, where the retinal vessels are readily visible through the pupil. Results are presented of preliminary experiments in normal persons, in whom an induced increased in intraocular pressure was associated with retinal vasodilatation.