Marked Constriction Research Articles

Activities of endothelin‐1 in the vascular network of the rabbit ear: a microangiographic study

1. The effects of endothelin-1 on perfusion pressure and on arterial and venous diameters were examined simultaneously in a rabbit isolated ear preparation perfused with physiological buffer. The effects of hypoxia and inhibition of endothelium-derived relaxant factor (EDRF) activity on vascular responses to endothelin-1 were also investigated. 2. Endothelin-1 was potent at increasing perfusion pressure (ED50 = 46.7 +/- 11.0 pmol; Rmax = 85.3 +/- 5.3 mmHg). The potency and maximum reactivity were not significantly affected by hypoxia, inhibition of EDRF activity with 50 microns N-nitro-L-arginine methyl ester (NAME) or a combination of hypoxia and NAME. 3. Endothelin-1 caused equipotent dose-dependent constrictions of the first four generations of arterial branch vessels (G1-G4) but did not influence the diameter of the central ear artery except at high doses of the peptide when paradoxical dilatation' was observed. The peptide was also equipotent at causing constriction of the smaller venous vessels (V1-V4) but did not affect the large veins (V0). 4. Under conditions of hypoxia the potency of endothelin-1 was reduced in G2 and G3, was unaffected in G4 and the peptide did not significantly constrict either G0 or G1. Hypoxia reduced the potency of endothelin-1 in the smaller venous vessels (V1-V4), but conversely unmasked a marked constriction of the large veins (V0), which was not observed under normoxic conditions. 5. NAME 50 micron abolished the vasodilator effects of acetylcholine in this preparation. Inhibition of EDRF activity with NAME under normoxic conditions did not influence the constrictor activity of endothelin-1 on the arterial or venous branch vessels. However, inhibition of EDRF activity under hypoxic conditions prevented the reduction of potency of endothelin-1 as a constrictor of arterial and venous branch vessels which occurred in hypoxia. In the presence of NAME endothelin-1 constricted VO in both normoxia and hypoxia with equipotency but the maximum effect was greatest in hypoxia. 6. In conclusion, endothelin-1 is a powerful vasoconstrictor which acts with greater potency in veins than arteries in the rabbit isolated ear. Although hypoxia does not influence pressor responses it nevertheless alters the spatial pattern of vasoconstriction. In particular hypoxia unmasks constriction of the large veins by endothelin-1. Constriction of these veins was also observed in the absence of EDRF in normoxia, but to a much lesser degree so that the effect of hypoxia may only be partially due to reduced EDRF activity. Hypoxia may therefore directly or indirectly increase the sensitivity of the main veins to endothelin-1.

Role of endothelium‐derived nitric oxide in the regulation of tonus in large‐bore arterial resistance vessels, arterioles and veins in cat skeletal muscle

The role of endothelium-derived nitric oxide in the regulation of vascular resistance (tonus) in cat skeletal muscle was studied with the use of NG-monomethyl-L-arginine (L-NMMA), a specific inhibitor of nitric oxide formation from L-arginine. The study was performed with a whole-organ technique which permits simultaneous, continuous and quantitative recordings of resistance reactions in the whole vascular bed (RT) and in its three consecutive sections: large-bore arterial resistance vessels (greater than 25 microns; Ra,prox), small arterioles (less than 25 microns; Ra,micro) and veins (Rv). NG-monomethyl-L-arginine (3-100 mg kg-1 tissue, i.a.) induced a dose-dependent increase in resistance that was preferentially, but not selectively, confined to the large-bore arterial resistance vessels. At a maximally effective dose (100 mg kg-1), the nitric oxide inhibitor caused a marked constriction, within 5 min, on average increasing RT by 99%, Ra,prox by 138%, Ra,micro by 18% and Rv by 23%. The constrictor response to NG-monomethyl-L-arginine was long-lasting but disappeared gradually over a period of about 1 h. However, it could be abruptly abolished by excess L-arginine (300 mg kg-1, i.a.). The vasodilator response (RT) to acetylcholine was significantly attenuated in the presence of NG-monomethyl-L-arginine compared with the control response. The results suggested that nitric oxide formation from L-arginine by the vascular endothelium plays a fundamental role in the regulation of vascular resistance (tone) in vivo, with its main site of action located in the large-bore arterial resistance vessels.

Effects of Platelet-Activating Factor on Myocardial Contraction and Myocardial Relaxation of Isolated Perfused Guinea Pig Hearts

Platelet-activating factor (PAF) is an important mediator of cardiovascular shock owing to immunologic reactions, including anaphylaxis and endotoxaemia. Previous studies have shown that PAF is a potent cardio-depressive agent causing a marked coronary constriction and a sustained impairment of myocardial contractility. In this study, we attempted to characterize further the prolonged PAF effects on coronary circulation and myocardial contractile force in isolated guinea pig hearts perfused at constant pressure (60 cm H2O) or constant flow which was adjusted to a level of 100% above basal flow. In addition, the PAF-induced changes of ventricular systolic and diastolic function were distinguished. In the hearts perfused at constant pressure, PAF induced a dose-dependent (0.57, 5.7, and 57 pmol/min) decrease of coronary flow rates, left ventricular pressure (LVP), LV contraction (peak positive dP/dt) and LV relaxation (peak negative dP/dt). The decrement of peak negative dP/dt was more pronounced than that of peak positive dP/dt. Maintenance of coronary flow rates only attenuated, but did not suppress, the PAF-induced ventricular malfunction, and it improved ventricular relaxation less than it did ventricular contraction. Pretreatment with the PAF antagonist WEB 2086 (19.7 nmol/min) almost completely abolished the effects of the highest PAF dose on coronary circulation and ventricular contractile parameters. We conclude that the cardiodepressive effects of PAF are due to coronary constriction and direct contractile events. Furthermore, PAF impairs ventricular diastolic function more than ventricular systolic function.

Effects of Endothelin-1 in Isolated Perfused Rat Heart

We examined the effects of the vasoconstrictor peptide endothelin-1 in the isolated heart and defined interactions of endothelin-1 with other hormone systems. Isolated isovolumic rat hearts were perfused with Krebs-Henseleit buffer at constant pressure. First, the effect of a single bolus of endothelin-1 (4-400 pmol) was followed for 90 min. The effect of high dosages (40 and 400 pmol) of endothelin-1 on coronary flow was biphasic, with an early vasodilator and a late vasoconstrictor component that was irreversible. Second, cumulative dose-response curves were obtained for endothelin-1 boluses of 0.04-400 pmol. Coronary flow declined with increasing dosages and was almost abolished at 400 pmol. Neither alpha- nor beta-blocking agents (phentolamine and propranolol) nor the Ca2(+)-channel blocker nifedipine altered the effects of endothelin-1, but prostaglandin synthesis inhibition by indomethacin significantly augmented vasoconstriction by endothelin-1. Angiotensin-converting enzyme (ACE) inhibition by captopril antagonized endothelin-1-dependent vasoconstriction to a small extent at 400 pmol. Coronary constriction due to endothelin-1 could not be reversed by nitroglycerin. We conclude that in isolated rat heart endothelin-1 causes marked and long-lasting coronary constriction. The effect is not influenced by sympathetic and Ca2(+)-channel blockade, is enhanced by prostaglandin synthesis inhibition, and is reduced by ACE inhibition.

Sports Hematuria

Strenuous exercise makes extraordinary demands. The transition from rest to intensive physical activity can cause pathological changes in various organs, particularly in the urinary tract. Hematuria (microscopic or macroscopic) is one of the abnormalities commonly found after sports activity. This phenomenon can occur in noncontact sports (such as rowing, running and swimming) as well as in contact sports (boxing, football and so forth). The pathophysiology can be either traumatic or nontraumatic. Renal trauma and/or bladder injury due to repeated impact of the posterior bladder wall against the bladder base can cause vascular lesions and consequently hematuria. There are 2 mechanisms of nontraumatic injury. 1) Vasoconstriction of the splanchnic and renal vessels occurs during exercise in order that blood can be redistributed to the contracting skeletal muscles, thus causing hypoxic damage to the nephron. This results in increased glomerular permeability which would favor increased excretion of erythrocytes and protein into the urine. 2) A relatively more marked constriction of the efferent glomerular arterioli results in an increased filtration pressure, which favors increased excretion of protein and red blood cells into the urine. It must be noted that sports hematuria differs from other conditions that may cause reddish discoloration of the urine due to physical exercise, such as march hemoglobinuria and exercise myoglobinuria. In the latter 2 abnormalities there is excretion of hemoglobin and myoglobin molecules in the urine and not whole blood or intact red blood cells. Sports hematuria usually has a benign self-limited course. However, coexisting urinary tract pathological conditions should be excluded carefully.

EFFECTS OF ENDOTHELIAL CELL REMOVAL ON α‐ADRENOCEPTOR‐MEDIATED RESPONSES OF AORTAE OF PREGNANT RATS

1. The possibility that changes in sensitivity of the aorta occurring during pregnancy in the rat are due to changes in uptake mechanisms, alpha- and/or beta-adrenoceptor-mediated responses was investigated. 2. Thoracic aortic rings from 20 day pregnant rats showed increased sensitivity to the constrictor effects of phenylephrine, with increased maximum responses when compared with those from non-pregnant animals. Removal of endothelium caused leftward shifts of the log concentration-response curves with further increases in maxima to the same extent in rings of both non-pregnant and 20 day pregnant rats. 3. Propranolol, beta-oestradiol, and nisoxetine did not significantly alter the CR-curves to phenylephrine of endothelium-intact or denuded thoracic aortic rings obtained from either non-pregnant or 20 day pregnant rats. 4. BHT-920 failed to cause marked constriction of endothelium-intact rings. After removal of endothelium, significant constrictor responses to BHT-920 occurred which were of similar magnitude for rings from both non-pregnant and 20 day pregnant rats. 5. Relaxant responses to BHT-920 of endothelium-intact rings preconstricted with phenylephrine were not significantly different between those from non-pregnant and 20 day pregnant rats. Removal of endothelium resulted in rightward shifts of the curves together with decreased maximum responses. 6. These results support earlier suggestions that the endothelium plays a role in controlling vascular reactivity to phenylephrine. The increased maximum response of thoracic aortic rings to phenylephrine seen during pregnancy does not appear to be due to marked changes in amine uptake mechanisms or beta- or alpha 2-adrenoceptor-mediated responses.

Calcitonin gene-related peptide-LI in subarachnoid haemorrhage in man. Signs of activation of the trigemino-cerebrovascular system?

Calcitonin gene-related peptide (CGRP) is a neurotransmitter candidate together with the tachykinins in sensory fibres in the cerebral vasculature, with possible vasodilating properties. The origin of most of the CGRP-immunoreactive cerebrovascular nerve fibres seems to be the trigeminal ganglion. Experimentally produced vasoconstriction in cats after lesions of the trigeminal ganglion have shown marked prolonged constriction compared to controls. The possible involvement of the trigemino-cerebrovascular system as a defence system, with CGRP probably being the more potent vasodilatator, was investigated in 12 patients with subarachnoid haemorrhage (SAH). After operation with clipping of the aneurysm and treatment according to department policy, blood samples were taken from the external jugular vein on postoperative days 1, 2, 3, 5, 7, 9, frozen and analysed (radioimmunoassay) for CGRP-LI (-like immunoreactivity) levels. The patients were monitored with Doppler recordings from the middle cerebral arteries (MCA) and internal carotid arteries (ICA) following blood sampling. The relationship Vmean MCA/V mean ICA was used as an index of vasospasm. The highest CGRP-LI levels were found in the patient with highest velocities/index values. In patients with MCA aneurysms (n = 7), a correlation of r = 0.61 was found between the index and CGRP-LI levels. However, significant changes in the group as a whole was not found. The possible involvement of the trigemino-cerebrovascular system in SAH is discussed.

Altered microvascular reactivity in streptozotocin-induced diabetes in rats

This study examined the effect of short-term streptozotocin-induced diabetes in rats on the response of cremaster muscle arterioles to angiotensin II (ANG II) and vasodilatory prostaglandins. Topically applied ANG II (10(-10) to 10(-6) M) caused significantly greater vasoconstriction of third-order arterioles in diabetic animals in comparison with controls. For example, in response to 10(-6) M ANG II arterioles of the diabetic animals constricted to 43 +/- 10% of basal diameter compared with controls' 67 +/- 6% (P less than 0.05). Furthermore, the magnitude of the secondary vasodilatation after ANG II-induced constriction was decreased in diabetic animals (108 +/- 4 and 131 +/- 9%, P less than 0.025). Cyclooxygenase inhibition resulted in marked arteriolar constriction, with this effect being less evident in diabetic animals. In response to indomethacin (2.8 x 10(-5) M), arterioles of the diabetic animals constricted to 84 +/- 7% of basal diameter compared with 56 +/- 4% in controls (P less than 0.01). Arterioles of the diabetic animals were less responsive to exogenous prostaglandin I2 (PGI2) and PGE2 (10(-12) to 10(-6) M) despite evidence of increased in vitro PGI2 production. The data demonstrate potentiation of the vasoconstrictor response and a diminution of the secondary vasodilator response to ANG II in experimental diabetes. These alterations may be due, in part, to decreased responsiveness of skeletal muscle arterioles to vasodilatory prostaglandins.

Vascular responses to leukocyte products in atherosclerotic primates.

Little is known about the possible role of leukocytes in the pathogenesis of vasospasm. We hypothesized that vasoactive products released by leukocytes might produce constriction of atherosclerotic arteries. To test this hypothesis, we infused fmet-leu-phe (fMLP), a peptide that activates leukocytes to release their vasoactive products, into the perfused hind limb of normal and atherosclerotic cynomolgus monkeys. Infusion of fMLP did not change resistance of large arteries in normal monkeys. In contrast, fMLP produced pronounced constriction of large arteries in atherosclerotic monkeys. To determine whether leukotrienes, platelet-activating factor, or prostaglandin E2 (PGE2), which are released by leukocytes, may contribute to leukocyte-induced vasoconstriction in atherosclerotic monkeys, we injected leukotriene D4, platelet-activating factor, and PGE2 intra-arterially into the perfused hind limb. Leukotriene D4 and platelet-activating factor had minimal effects on large arteries in both normal and atherosclerotic monkeys. PGE2 produced marked constriction of large arteries in atherosclerotic, but not normal, monkeys. Thus, pronounced constriction in atherosclerotic, but not normal, arteries during infusion of fMLP suggests that products released by leukocytes may mediate vasoconstriction in atherosclerotic vessels. Vasoconstrictor responses to PGE2 are profoundly potentiated by atherosclerosis, which suggests that PGE2 may contribute to leukocyte-induced vasoconstriction.

Lipoxygenase metabolites in the rat gastric microvascular response to intragastric ethanol

The role of lipoxygenase metabolites in ethanol-induced gastric mucosal injury and submucosal microvascular change in the rat was studied by in vivo microscopy. Intragastric ethanol instillation caused marked submucosal venular constriction, dilatation of small arterioles, and corpus mucosal gross lesion formation. The venoconstriction was greater in the lesion than in the nonlesion area. Intragastric pretreatment with either BW755C, a lipoxygenase inhibitor, or Rioprostil, a synthetic prostaglandin E1 analogue, significantly inhibited both the ethanol-induced venoconstriction and the gross lesion formation. In contrast, pretreatment by the submucosal application of either BW755C (50 μg/ml) or Rioprostil (50–500 ng/ml) had no effect on either the submucosal venoconstriction or the mucosal lesion formation. In conclusion, leukotrienes released from the gastric mucosa appear to be involved in the ethanol-induced submucosal venoconstriction associated with gastric mucosal injury. Prostaglandin pretreatment protects against this venoconstriction and gross lesion by a mucosal effect but not by a direct effect on submucosal venules.

Involvement of D1 and D2 Dopamine Receptors in the Control of Horizontal Cell Electrical Coupling in the Turtle Retina

We studied the actions of D1 and D2 dopamine agonists and antagonists on the coupling of horizontal cell axons in the turtle retina by a combination of pharmacological and electrophysiological methods. Both D1 and D2 receptors were identified in membrane fractions by radioligand binding using [3H]-SCH 23390 and [3H]-spiperone, respectively. The KD of both receptor classes were identical (0.21 nM) but D1 receptor density exceeded that of D2 receptors by more than four-fold. D1 agonists increased the activity of adenylate cyclase in a dose-dependent manner, whereas D2 agonists were without significant effect by themselves, nor did D2 antagonists block the D1-mediated increase in adenylate cyclase activity. Intracellular recordings and Lucifer Yellow dye injections were used to characterize the modifications of the receptive field profile of horizontal cell axons (H1AT) exposed to different pharmacological agents. Dopamine or D1 agonists (0.05 - 10 microM) induced a marked constriction of the H1AT receptive field, whereas D2 agonists elicited a small expansion of the receptive field. However, in the presence of a D1 antagonist, as well as IBMX to inhibit phosphodiesterase, D2 agonists (10 - 70 microM) induced a marked increase in the receptive field profile. These results indicate that both D1 and D2 dopamine receptors play a role in shaping the receptive field profile of the horizontal cell axon terminal in the turtle retina.

The influence of extracellular calcium on microvascular tone in the rat cremaster muscle.

In vivo responses of arterioles and venules to changes in bath calcium concentrations were observed in the cremaster muscle of male Sprague-Dawley rats. Small arterioles (2A, 3A) initially exposed to a solution containing calcium (2.55 mM) significantly dilated in response to a 0-calcium bath. Reexposure to calcium (greater than 0.65 mM) caused 2A and 3A arterioles to constrict to diameters similar to the initial control values. In contrast, large arterioles (1A) and all venules (1V, 2V, 3V) were unresponsive to exposure to a 0-calcium solution or to reexposure to calcium (0.65-5.10 mM). Treatment with mefenamic acid (10 micrograms/ml), a prostaglandin synthesis inhibitor, produced marked constriction of arterioles but not of venules, suggesting the involvement of endogenous vasodilator prostaglandins in the regulation of resting diameters of arterioles. In the presence of mefenamic acid, 1A arterioles dilated when exposed to a 0-calcium solution and constricted back to control diameters following reintroduction of calcium into the bath. These data demonstrate heterogeneity in the responsiveness of cremasteric microvessels to changes in extracellular calcium. The small arterioles were most responsive to calcium. The lack of response by the largest arterioles appears to be due to the dilator influences of endogenous prostaglandins.

The blood vascular architecture of the rat pineal gland: a scanning electron microscopic study of corrosion casts.

The blood vascular bed of the rat pineal gland was reproduced through a low viscosity methacrylate casting medium and observed with a scanning electron microscope. The pineal gland was located in front of the confluens sinuum which was formed by the confluence of the left and right transverse sinuses and the superior sagittal and great cerebral veins. The pineal gland was found to contain a rich vascular network of freely anastomosing capillaries. This network received a few afferent arteries from the posterior cerebral arteries while emitting ten to fifteen efferent veins. Most of these efferent veins drained into the upper segment of the great cerebral vein; the remaining one or two efferent veins continued directly into the confluens sinuum. A marked constriction, probably representing a venous valve or valve-like projection, was observed in the opening area of the great cerebral vein. Circular constrictions, probably representing sphincters, were imprinted in the efferent vessels. No direct vascular connection was noted between the pineal gland and the nervous tissues or between the pineal gland and the choroid plexuses of the third and lateral ventricles.

Responses of coronary arteries of cardiac transplant patients to acetylcholine.

Accelerated coronary atherosclerosis is a major cause of graft failure after heart transplantation. Graft atherosclerosis is typically diffuse and difficult to detect even with coronary arteriography. Recently, acetylcholine was shown to dilate blood vessels by releasing a vasorelaxant substance from the endothelium (endothelium-derived relaxing factor). We have demonstrated paradoxical vasoconstriction induced by acetylcholine both early and late in the course of coronary atherosclerosis in patients, suggesting an association of endothelial dysfunction and atherosclerosis. In this report, we tested the hypothesis that coronary arteries of heart transplant patients can show endothelial dysfunction before or in the early stages of angiographically evident coronary atherosclerosis. Acetylcholine was infused into the left anterior descending artery of 13 heart transplant patients at 12 (n = 9) and 24 (n = 4) mo after transplantation. Vascular responses were evaluated by quantitative angiography. Among patients with angiographically smooth coronary arteries, relatively few (6/25) arterial segments had preserved vasodilator responses, while the majority failed to dilate (10/25) or paradoxically constricted (9/25). Angiographically irregular coronary arteries were present in three patients, in whom 8/10 segments showed marked paradoxical constriction and the remaining 2/10 failed to dilate. Only 1 of 13 patients retained appropriate dilation to acetylcholine in all segments. Nitroglycerin, which acts directly on vascular smooth muscle, dilated nearly all segments. No clinical features of the patients, including myocardial rejection appeared to correlate with the impaired functional response of vessels. Thus impaired response to acetylcholine is a common early finding in heart transplant patients and emphasizes the potential importance of endothelial dysfunction in the development of atherosclerosis.

Healing and Long-Term Viability of Grafts in the Venae Cavae Reconstruction

The need for superior vena cava (SVC) or inferior vena cava (IVC) recon struction is not uncommon: lung cancer, mediastinal tumors, or retroperitoneal neoplasms are the most frequent indications for caval replacement. Since auto genous veins, which represent the most satisfactory venous substitute, have not been applicable to caval replacement, because of the lack of suitable length and caliber, many types of materials have been tested in the venous system. The present study was planned to compare the potential of expanded polytetrafluoroethylene (e-PTFE) and glutaraldehyde-tanned human umbilical vein (HUV) grafts as caval substitutes. Patch (4 x 5 cm) reconstruction of the SVC was carried out in 10 dogs, tubu lar (3 x 10 mm) reconstruction of the SVC in 5 dogs, and patch (1 x 2 cm) recon struction of the IVC in 8 dogs. In the patch reconstruction groups, HUV grafts were used in half of the cases and 30 μm pore sizes e-PTFE grafts in the other half, while in the tubular SVC replacement group, only e-PTFE grafts were employed. The grafts were removed fifteen to thirty days after IVC patch re construction, thirty to two hundred seventy days after SVC patch reconstruc tion, and thirty-three to forty-one months after SVC tubular replacement. In every instance, specimens were obtained for light microscopy (LM) and scan ning electron microscopy (SEM). HUV patches implanted in the SVC showed hemorrhagic foci at their central portion and marked constriction at the anastomotic regions. On the contrary, the inner surface of e-PTFE patch grafts was covered with a uniform and glis tening neointima. By LM, e-PTFE patches showed a smooth and regular lumi nal surface, while the inner surface of HUV patches was irregular, with hemorrhagic areas in the underlying layers. By SEM, e-PTFE patches revealed a more rapid and orderly endothelialization of their inner surface than HUV patches did. Tubular SVC reconstruction showed the good long-term viability of the e-PTFE neointima (as long as forty-one months after grafting). Only spotty areas revealed neointima alterations, such as fibrinoid degeneration, fo cal necrosis, or minor thrombotic foci. In the IVC patch reconstruction model, HUV grafts showed an exuberant fibrin deposition on their inner surface and delayed endothelialization patterns, as compared with e-PTFE grafts. Since rapid healing with rapid endothelialization is accepted as the most important factor providing the graft luminal surface with the best antithrombotic proper ties, the present study demonstrated that e-PTFE is a more suitable material than HUV for SVC and IVC reconstruction.

Supraglottic contribution to voice quality

Summary Although there has been continuing interest in voice quality, much of this research has focused on the vocal folds rather than the supraglottal structures. This paper reports the use of videoendoscopy for studying supraglottal participation in various singing tasks. In a preliminary study presented last year by the present authors, CT scanning was used to corroborate videoendoscopic observation. Vocal tract activities observed included variation of laryngeal height with pitch, variation of pharyngeal wall dimension with pitch and vowel, and marked supraglottic constriction with certain vocal imitations. In order to gain a better understanding of vocal training, and its effect upon vocal tract physiology, a study was designed using videoendoscopy to observe singers with significant experience and training while performing various vocal tasks. The tasks focused on the following: (1) vocal tract activity associated with pitch changes; (2) the physiology involved in the production of “cover”; (3) the structures involved in the production of vibrato; and (4) the physiology of the singer's “ring.” It would appear that videoendoscopy will become increasingly more valuable to the voice community as our understanding of vocal tract physiology improves.

Renovascular effects of adenosine receptor agonists.

The purpose of the present experiments was to determine the renovascular effects of the adenosine agonists N-ethyl-carboxamide adenosine (NECA), N6-cyclohexyl adenosine (CHA) and 2-chloro adenosine (2-CLA). The diameter of pre- and postglomerular vessels in the split hydronephrotic kidney of Inactin-anesthetized rats was measured by in vivo television microscopy. All metabolically stable adenosine agonists were topically applied into the renal tissue bath. NECA, a preferential A2 adenosine receptor agonist, induced dose-dependent marked pre- and slight postglomerular vasodilation except for a small constrictory effect on the afferent arteriole near the glomerulus. Application of CHA, a selective A1 adenosine receptor agonist, led to a vasoconstriction of all preglomerular vessels, the extent of which was greatest at the most distal segment of the afferent arteriole. 2-CLA, a nonselective agonist, produced a small decrease in diameter in all preglomerular vessels, a marked constriction of the afferent arteriole at sites near the glomerulus, and a slight dilation of postglomerular vessels. Glomerular blood flow (GBF) was increased by NECA, and decreased by CHA and 2-CLA. The effects of CHA in reducing GBF were greater than those of 2-CLA. From these experiments it is concluded that vascular A1 and A2 adenosine receptors are present in the kidney and that activation of A1 receptors is associated with preglomerular vasoconstriction only, whereas activation of A2 receptors mediates pre- and postglomerular vasodilation with a lack of vasodilatory response of the distal afferent arteriole. Furthermore, these data indicate that nonselective occupation of both receptor subclasses is associated with marked vasoconstriction of the afferent arteriole and little vasodilation of the efferent arteriole.

Acute toxic blindness: Unrecognized quinine poisoning

Two cases of acute blindness due to quinine poisoning are presented. In both cases, the diagnosis was initially unsuspected. In addition, tinnitus, decreased hearing, vomiting, abdominal pain, and confusion were noted in one patient, and the other experienced decreased hearing, headache, confusion, tachycardia, later bradycardia, and first-degree atrioventricular block. The onset of blindness was delayed more than 12 hours after ingestion in both cases. Quinine levels of 13.6 micrograms/mL and 18.6 micrograms/mL were demonstrated (therapeutic = 1 to 3 micrograms/mL). One patient developed marked constriction of visual fields and some residual decreased acuity, while the other regained normal visual acuity.

MRI of the Budd-Chiari syndrome

Five of six patients with angiographically proved Budd-Chiari syndrome (hepatic venous outflow obstruction) showed multiple specific MRI abnormalities: striking reduction in caliber or complete absence of the hepatic veins, "comma-shaped" intrahepatic collateral vessels, and/or marked constriction of the intrahepatic inferior vena cava. The sixth patient had angiographically proven sinusoidal hepatic venous obstruction and patent central hepatic veins; MRI showed ascites but revealed no specific features of the Budd-Chiari syndrome. Patients with end-stage cirrhosis also showed compressed, distorted hepatic veins; however, these cirrhotic livers were distinguished by their small size, nodular surface, and extrahepatic collateral varices. In patients without cirrhosis or the Budd-Chiari syndrome, normal hepatic, portal, and inferior caval veins were routinely seen when technically adequate MRI examinations were obtained (94 of 100 cases). Four of the six patients with Budd-Chiari syndrome had been treated surgically. In three, MRI identified patent portocaval shunts. In the fourth, angiographically confirmed shunt stenosis was demonstrated by MRI.

Propalorchestes novaculacephalus gen. e tet sp.nov., a new palorchestid (Diprotodontoidea: Marsupialia) from the Middle Miocene Camfield Beds, Northern Territory, Australia

Propalorchestes novaculacephalus gen. et sp.nov. is a comparatively small Ngapakaldia Stirton-like diprotodontoid marsupial represented by an edentulous, extremely narrow, high braincase fragment with a marked postorbital constriction n. Details of its cranial base, glenoid fossa morphology and auditory region indicate that it is aligned with the Palorchestinae. The overall morphology of P. novaculacephalus braincase morphology emphasizes the uniqueness of this evolutionary lineage of marsupials.