Triple-deck analysis of transonic high Reynolds number flow through slender channels.

In this work, laminar transonic weakly three-dimensional flows at high Reynolds numbers in slender channels, as found in microsupersonic nozzles and turbomachines of micro-electro-mechanical systems, are considered. The channel height is taken so small that the viscous wall layers forming at the channel walls start to interact strongly rather than weakly with the inviscid core flow and, therefore, the classical boundary layer approach fails. The resulting viscous-inviscid interaction problem is formulated using matched asymptotic expansions and found to be governed by a triple-deck structure. As a consequence, the properties of the predominantly inviscid core region and the viscous wall layers have to be calculated simultaneously in the interaction region. Weakly three-dimensional effects caused by surface roughness, upstream propagating flow perturbations, boundary layer separation as well as bifurcating solutions are discussed. Representative results for subsonic as well as supersonic conditions are presented, and the importance of these flow phenomena in technical applications as, for example, a means to reduce shock losses through the use of deformed geometry is addressed.

Evaluation of robotic assistance in neurosurgical applications.

An analysis of usability aspects and accuracy for three different methods of neurosurgical intervention-stereotaxy, neuro-navigation, and robotic assistance-was accomplished in a detailed study including clinicians with different experience levels. Accuracy tests with a specially designed phantom were performed under clinical conditions according to EN ISO 9283. Test scenarios were designed according to a realistic clinical work-flow for the brain biopsy process. This paper presents the results of the accuracy evaluation as well as a discussion of the results and further steps.

Neuropathology of chronic GM2 gangliosidosis due to hexosaminidase A deficiency.

Autopsy studies of late-onset GM2 gangliosidosis are sparse and only one adult case is on record. The case of partial Hex A deficiency presented here started in childhood as spinal muscular atrophy which progressed slowly over 4 decades. Cognitive function remained intact throughout the entire course, but during the last few years of life allodynia supervened. The patient died at 44 years of age. In good correlation with clinical observations the autopsy findings showed the most severe accumulation of lipid and consequent regressive change in the anterior horns of the spinal cord. Extensive but less severe storage was found in other spinal cord neurons, brain stem and selected basal ganglia. Cerebral cortex was virtually spared by storage but was the site of excessive formation of lipofuscin which was also present in many other neurons in the CNS. Marked storage and ganglionic loss was also found in the dorsal root ganglia, and the fasciculus gracilis was severely depleted of myelinated fibers. Electron microscopy showed accumulated gangliosides almost exclusively in the form of single and coalescing zebra bodies. In conclusion, the pathology in this case of chronic GM2 gangliosidosis, though in part conforming with previous observations, differed in several aspects. First, the cerebral cortex was--with only a few exceptions--free of ganglioside storage. Also spared was the cerebellum. In addition, homogeneous accumulation of zebra bodies contrasted with heterogeneity of neuronal inclusions found in other chronic cases. Finally, the involvement of sensory neurons was prominent and potentially related to allodynia. Molecular study of HEXA gene in this patient showed an TATC1278/? genotype.

Risk analysis and safety assessment in surgical robotics: a case study on a biopsy robot.

One of the most important issues in medical robotics is safety and integration into the clinical workflow. If a robot is not safe and its use is complicated by difficult handling and complex user interfaces physicians would not use a robotic system during clinical patient trials, whatever the other advantages are. However, there are only few publications on this topic, in particular on risk management in developing a robotic prototype (for clinical trials). In this paper risk management and the safety of using robot-assisted surgery equipment are discussed and demonstrated exemplarily in the process of developing a prototype biopsy robot.

Cerebral phaeohyphomycosis caused by a dematiaceous scopulariopsis species.

This report describes a rapidly fatal case of cerebral phaeohyphomycosis in a 33-year-old immunocompetent male. The infection presented as a single large lesion in the deep white matter of one temporal lobe, which was then removed surgically. Histologic features observed in the lobectomy specimen were characterized by perivascular sleeves of mononuclear cells accompanied by hemorrhages. These were reminiscent of acute hemorrhagic leukoencephalitis except for the presence of rare fungal organisms and sparse multinucleated giant cells similar to those occurring in AIDS. During the four days following surgery, a large focus of cerebritis with massive invasion of fungi developed in each centrum semiovale around the ventriculostomy sites. Fungal culture of the brain obtained at autopsy grew an organism consistent with a Scopulariopsis species.

Experimental influenza B viral myositis.

To investigate the pathogenesis of influenza myositis in animals, juvenile BALB/c mice were inoculated with influenza B/Lee virus intramuscularly into the right quadriceps muscle. Chicken normal allantoic fluid (NAF) or phosphate-buffered saline (PBS) was injected into the left quadriceps of control mice and in some virus-infected mice. Serum creatinine phosphokinase (CPK) levels rose significantly on days 1 and 2 post-inoculation (PI) in only virus-inoculated mice. On days 2 and 3 PI, right quadriceps muscles developed scattered foci of a predominantly mononuclear inflammation in the perimysial connective tissue often adjacent to degenerating or necrotic muscle fibers. Immunofluorescent staining with specific anti-influenza B virus antisera showed muscle fibers that contained specific staining in nuclei and adjacent cytoplasm. Skip areas of staining within muscle fibers suggested that not all muscle nuclei within an individual muscle fiber were infected. A continuous fall in infectious virus titer in the right quadriceps muscles suggested the initial virus inoculum became inactivated and progeny virions were not produced. Left quadriceps muscle never had muscle necrosis or endomysial inflammation, specific staining of viral antigen, virus isolation, or viral RNA detected by the reverse transcriptase polymerase chain reaction assay. These findings support the hypothesis that a non-permissive influenza viral infection can develop in murine skeletal muscle that can damage specific nuclear domains of muscle fibers producing muscle degeneration or necrosis. A similar type of muscle infection may develop in humans that occasionally develop focal myositis during influenza.

Lung cancer in a nonsmoking underground uranium miner.

Working in mines is associated with acute and chronic occupational disorders. Most of the uranium mining in the United States took place in the Four Corners region of the Southwest (Arizona, Colorado, New Mexico, and Utah) and on Native American lands. Although the uranium industry collapsed in the late 1980s, the industry employed several thousand individuals who continue to be at increased risk for developing lung cancers. We present the case of a 72-year-old Navajo male who worked for 17 years as an underground uranium miner and who developed lung cancer 22 years after leaving the industry. His total occupational exposure to radon progeny was estimated at 506 working level months. The miner was a life-long nonsmoker and had no other significant occupational or environmental exposures. On the chest X-ray taken at admission into the hospital, a right lower lung zone infiltrate was detected. The patient was treated for community-acquired pneumonia and developed respiratory failure requiring mechanical ventilation. Respiratory failure worsened and the patient died 19 days after presenting. On autopsy, a 2.5 cm squamous cell carcinoma of the right lung arising from the lower lobe bronchus, a right broncho-esophageal fistula, and a right lower lung abscess were found. Malignant respiratory disease in uranium miners may be from several occupational exposures; for example, radon decay products, silica, and possibly diesel exhaust are respiratory carcinogens that were commonly encountered. In response to a growing number of affected uranium miners, the Radiation Exposure Compensation Act (RECA) was passed by the U.S. Congress in 1990 to make partial restitution to individuals harmed by radiation exposure resulting from underground uranium mining and above-ground nuclear tests in Nevada.

The influence of beta-adrenergic activation on noradrenergic alpha1 activation of rabbit afferent arterioles.

The aim of the present investigation was to examine the effect of beta-adrenergic stimulation on smooth muscle calcium concentration ([Ca2+]i) in resting conditions and after administration of norepinephrine (NE) to stimulate alpha-adrenoceptors in isolated rabbit afferent arterioles loaded with the calcium-sensitive fluorescent probe fura-2. [Ca2+]i was evaluated in the proximal and distal parts of the arterioles. NE (4x10(-7) M) increased [Ca2+]i in both these regions. The alpha1-adrenoceptor antagonist prazosin (10(-7) M) totally abolished the NE-induced increase in [Ca2+]i, while the alpha2-adrenoceptor antagonist yohimbine (5x10(-7) M) had no influence on the response to NE. When beta-adrenoceptors were stimulated, using isoproterenol (10(-7) M), the NE-induced increase in [Ca2+]i was significantly lower in both regions. Activation of beta-adrenoceptors with isoproterenol did not affect the [Ca2+]i increase in response to depolarization with K+. Since beta-adrenoceptor stimulation raises the smooth muscle cell levels of cAMP, an adenylate cyclase stimulator, forskolin (10(-5) M) was administered prior to NE application. This maneuver also blunted the increase in [Ca2+]i in both regions. We conclude that the calcium response to NE in the isolated rabbit afferent arteriole is mediated by an alpha1-adrenoceptor. beta-Adrenoceptor stimulation and forskolin blunt the increase in [Ca2+]i induced by NE stimulation, indicating that cAMP counteracts the NE-induced activation of alpha1-adrenoceptors.

Experimental influenza causes a non-permissive viral infection of brain, liver and muscle.

To determine whether some constitutional symptoms of influenza, such as headache, myalgia and nausea, could represent a viral infection of brain, muscle, and liver, we inoculated juvenile Balb/c mice intranasally with 103 plaque forming units of influenza B/Lee virus. Blood, brain, liver, skeletal muscle, and lung tissues were removed aseptically and assayed for infectivity by a plaque assay, viral RNA by reverse transcriptase-polymerase chain reaction (RT - PCR), viral antigen by immunoperoxidase staining, and histologic changes by light microscopy. Mice became ill 2 - 3 days post inoculation (PI). A productive viral infection of the lungs developed from days 1 - 8 with maxima of virus titers, pneumonia, and the number of immunoperoxidase staining lung cells occurring on days 2 - 6 PI. Virus isolation from blood was rare and viral RNA was detected intermittently in blood by RT - PCR. In many animals, a non-permissive or abortive infection of brain occurred from days 1 - 8 and peaked on days 3 - 4 PI. Viral RNA was detected in brain tissue and viral antigen was seen in cerebral endothelial cells but infectious virus was rarely isolated from brain. In liver, viral RNA was detected and viral antigen was seen occasionally in hepatocytes. In skeletal muscle, viral RNA was detected but neither infectious virus nor viral antigen was seen. A correlation existed between the severity of the illness, pneumonia, lung virus titer, viral antigen in lung cells, and extent of a non-permissive viral infection of brain and liver but not muscle. These studies demonstrate that following intranasal infection of influenza virus in mice, a viral pneumonia develops with subsequent intermittent viremia and non-permissive or abortive infection of brain, liver and muscle.

Calcium response to adenosine and ATP in rabbit afferent arterioles.

The effects of purine compounds in the renal vasculature are almost exclusively restricted to pre-glomerular vessels. Although their physiological role as extracellular messengers is not clear, there are extensive data indicating the importance of adenosine and ATP in the regulation of renal haemodynamics. This study was undertaken to characterize the calcium response of rabbit afferent arteriole to adenosine, ATP and other nucleotides. Experiments were performed in isolated afferent arterioles, microdissected from rabbit kidneys and loaded with fura-2. Intracellular calcium concentration ([Ca2+]i) was measured by video in proximal and distal parts of the afferent arteriole. Application of 100 microM adenosine or ATP increased [Ca2+]i in both arteriolar regions. In all cases the response had two well distinguishable phases: a quick peak increase and a plateau phase that equilibrated at a [Ca2+]i significantly higher than the basal level. UTP (100 microM) had no effect on the arteriole. Removal of extracellular calcium (2.5 mM EGTA) abolished only the plateau phase in response to adenosine, without significantly changing the peak increase. In contrast, the response to ATP was completely abolished in both arteriolar regions, where [Ca2+]i decreased upon application of the agonist and rapidly increased after restoration of calcium concentration to plasma level. We conclude that P1 and P2X receptors are present along the rabbit afferent arteriole and mediate calcium mobilization, with the same distribution in the proximal and distal segments.

Nitric oxide/cAMP interactions in the control of rat renal vascular resistance.

This study aimed to characterize the interaction between nitric oxide (NO)- and cAMP-related pathways in the control of renal blood flow. Using the isolated perfused rat kidney model, we determined the effects of inhibition of NO formation by Nomega-nitro-L-arginine methyl ester (L-NAME; 1 mmol/L) and of NO administration by sodium nitroprusside (SNP, 10 micromol/L) on renal vascular resistance under conditions of elevated vascular cAMP levels. cAMP levels were increased either by adenylate cyclase activation via isoproterenol or by inhibition of cAMP phosphodiesterases (PDEs) 1, 3, and 4. We found that L-NAME markedly increased vascular resistance and that this effect was completely reversed by SNP. Both isoproterenol and inhibitors of the cAMP PDEs lowered basal vascular resistance. In the presence of isoproterenol (3 nmol/L) and inhibitors of PDE-1 [8-methoxymethyl-l-methyl-3-(2-methylpropyl)-xanthine; 8-MM-IBMX, 20 micromol/L] and PDE-4 (rolipram, 20 micromol/L), L-NAME again substantially increased vascular resistance, and this effect of L-NAME was completely reversed by SNP. In the presence of the PDE-3 inhibitors milrinone (20 micromol/L) and trequinsin (200 nmol/L), however, both L-NAME and SNP failed to exert any additional effects. Because PDE-3 is a cGMP-inhibited cAMP PDE and because the vasodilatory effect of SNP was abrogated by the guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one (ODQ) (20 micromol/L), our findings are compatible with the idea that an action of NO on PDE-3 could account for the vasodilatory properties of NO on the renal vasculature. Moreover, our findings suggest that PDE-3 activity is an important determinant of renal vascular resistance.

AT1 receptor inhibition blunts angiotensin II-stimulated nitric oxide release in renal arteries.

Nitric oxide (NO) is known to modulate the vascular effects of angiotensin II (AngII) in the kidney. To investigate the effect of AngII on NO release, a new technique was used that employs an NO-sensitive microelectrode to measure NO release from the vascular endothelium of perfused renal resistance arteries (tertiary branches of the renal artery or primary arcuate arteries) in vitro. The vessels were microdissected from isolated perfused rat kidneys, cannulated, and perfused at constant flow and pressure with Krebs-Ringer bicarbonate solution. The electrode was placed inside the glass collection cannula to measure vessel effluent NO concentration. Addition of AngII to the perfusate stimulated NO release in a dose-dependent manner; 0.1, 10, and 1000 nM AngII increased NO oxidation current by 85+/-18 pA (n=11), 148+/-22 pA (n=11), and 193+/-29 pA (n=11), respectively. These currents correspond to changes in effluent NO concentration of 3.4+/-0.5, 6.1+/-1.1, and 8.2+/-1.3 nM, respectively. The presence of 0.1 mM N(G)-nitro-L-arginine methyl ester in the perfusate significantly reduced the response to 10 nM AngII by 90.5+/-3.4% (n=5). Neither losartan (1 microM) nor candesartan (1 nM) significantly affected basal NO production, but both of these AT1-receptor blockers markedly blunted NO release in response to AngII (10 nM): 77+/-6% inhibition with losartan (n=8) and 63+/-9% with candesartan (n=8). These results demonstrate that AngII stimulates N(G)-nitro-L-arginine methyl ester-inhibitable NO release in isolated renal resistance arteries. Because the response was significantly blunted by AT1 receptor blockade, the findings suggest that endothelium-dependent modulation of AngII-induced vasoconstriction in renal resistance arteries is mediated, at least in part, by AT1 receptor-dependent NO release.

Radiation-induced blood-brain barrier damage in astrocytoma: relation to elevated gelatinase B and urokinase.

Successful management of brain tumors prolongs life, raising the risk of delayed injury secondary to the treatment. Radiation therapy, a mainstay of brain tumor treatment, can damage the cerebral blood vessels. Acutely a breakdown of the blood-brain barrier (BBB) may be seen, but fibrosis complicates radiation injury in the chronic phase. Matrix metalloproteinases (MMPs) and plasminogen activators are two matrix-degrading proteolytic enzymes, which are induced by radiation. They disrupt the basal lamina around cerebral capillaries and open the BBB. We report a patient with an astrocytoma managed by partial resection and external beam irradiation to maximal tolerable doses. The patient later developed malignant brain edema shortly after stereotactic radiosurgery. Tissue obtained during surgical debulking to control the edema showed very high levels of gelatinase B (92 kDa type IV collagenase) and urokinase-type plasminogen activator (uPA). Tumor cells were absent from the biopsy and subsequent autopsy specimens, but necrosis with fibrosis of the blood vessels was seen. If abnormal matrix enzyme function participates in the expression of radiation injury, then inhibitors to such enzymes may provide one strategy for controlling cerebrovascular damage after therapeutic brain radiation.

Medición del riesgo funcional en adultos mayores pobres, con un instrumento validado en Canadá / Functional risk assessment of poor Chilean elders using an instrument validated in Canada

Background: Information about medical and social situation of elders is limited in Chile. Aim: To assess the functional risk of Chilean elders using an instrument validated in Canada. Subjects and methods: As part of a project aimed to help poor elders, 2,116 subjects living in Santiago, aged 65 to 99 years old (1,334 female, and 625 older than 75 years old), were interviewed. Results: Thirty percent of these elders were using more than three medications and 13 percent lived alone. Visual problems were detected in 75 percent, memory problems were found in 62 percent, 63 percent felt depressed, 46 percent had hearing problems, 42 percent suffered a fall during the last year, 35 percent had a health problem that forced them to stay at home, 32 percent did not count with help in a case of need, 33 percent referred some type of nutritional problem, 26 percent needed help for daily living activities and 25 percent considered to have a worst health than counterparts of the same age. Among subjects older than 75 years old, the frequency of memory problems, auditory impairment, number of falls, health problems that precluded leaving the house, limitation for daily activities and the use of walking aids, was significantly higher. Although men and women had similar ages, men were in worst functional conditions, and had required more admissions to hospitals. There was a higher proportion of women living alone. Females also had a higher frequency of depression, memory disturbances, falls and use of more than three medications. Conclusions: Women elders tend to be in better functional conditions than men and people older than 75 years old have a higher functional risk. The applied instrument allowed a better focalization of our geriatric program

Valoración geriátrica ambulatoria de 2116 adultos mayores pobres / Geriatric assessment of 2116 free living elders

Background: Geriatric assessment quantifies medical, functional, mental and social capabilities and alterations of elders and is the first step to initiate specific intervention programs. Aim: To report the initial geriatric assessment of a program aimed to help poor elders living in Metropolitan Santiago. Subjects and methods: Two thousand one hundred sixteen free living subjects aged 65 to 99 years old (711 males) were subjected to an assessment using a simple geriatric score validated abroad and used previously in Chile. The resulting score ranges from 0 (better) to 5 (worst). Results: Eighty eight percent of elders did not have problems in the functional evaluation. Subjects over 75 years old needed occasional support for the daily activities with higher frequency than younger subjects (12 and 5.4 per cent respectively, p< 0.001) and had a higher frequency of major functional limitations (7.8 and 3.2 per cent respectively, p< 0.001). Mental assessment was considered normal in 89.4 per cent of subjects. Those over 75 years old had a higher frequency of memory disturbances (11.4 and 6.5 per cent respectively) and cognitive alterations (4.6 and 1.8 per cent respectively). Indefinite social support could be received by 84 per cent of subjects, but 7.4 per cent did not have access to this resource. Conclusions: Geriatric assessment of poor elders gives useful information to identify those subjects that require community help

Autosomal dominant cerebral arteriopathy: neuropsychiatric syndrome in a family.

Though familial vascular leukoencephalopathy was described two decades ago, recent studies focus on a disorder termed Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL), a dominantly inherited disorder causing recurrent strokes and eventual dementia. The phenotypic boundaries of CADASIL remain indistinct and novel clinical features continue to arise in the literature. However, the associated histopathology is fairly consistent, typically demonstrating granular thickening of cerebral arterioles. The authors evaluated a 38-year-old man who suffered from progressive change in personality and intellect. His father, paternal aunt, and older sister had succumbed to a similar disorder. The authors examined relatives from three generations, including another sister with transient focal symptoms followed by persisting psychiatric disorder, and reviewed the radiographic studies from the propositus and his siblings. All the siblings showed diffuse white matter signal change on magnetic resonance imaging. Brain biopsy from the propositus revealed normal cortex and white matter but granular sclerosis of leptomeningeal arterioles. While the family's illness likely represents another instance of CADASIL, their presentation is unique because neuropsychiatric disorders predominate over focal ischemic symptoms.

Angiotensin-II stimulates nitric oxide release in isolated perfused renal resistance arteries.

Nitric oxide (NO) has been implicated as a modulator of the vascular effects of angiotensin II (ANG II) in the kidney. We used a NO-sensitive microelectrode to study the effect of ANG II on NO release, and to determine the effect of selective inhibition of the ANG II subtype I receptor (AT1) with losartan (LOS) and candesartan (CAN). NO release from isolated and perfused renal resistance arteries was measured with a porphyrin-electroplated, carbon fiber. The vessels were microdissected from isolated perfused rat kidneys and perfused at constant flow and pressure in vitro. The NO-electrode was placed inside the glass collection cannula to measure vessel effluent NO concentration. ANG II stimulated NO release in a dose-dependent fashion: 0.1 nM, 10 nM and 1000 nM ANG II increased NO-oxidation current by 85+/-18 pA (n = 11), 148+/-22 pA (n = 11), and 193+/-29 pA (n = 11), respectively. These currents correspond to changes in effluent NO concentration of 3.4+/-0.5 nM, 6.1+/-1.1 nM, and 8.2+/-1.3 nM, respectively. Neither LOS (1 muM) nor CAN (1 nM) significantly affected basal NO production, but both AT1-receptor blockers markedly blunted NO release in response to ANG II (10 nM): 77+/-6% inhibition with LOS (n = 8) and 63+/-9% with CAN (n = 8). These results are the first to demonstrate that ANG II stimulates NO release in isolated renal resistance arteries, and that ANG II-induced NO release is blunted by simultaneous AT1-receptor blockade. Our findings suggest that endothelium-dependent modulation of ANG II-induced vasoconstriction in renal resistance arteries is mediated, at least in part, by AT1-receptor-dependent NO release.

Fibrocartilagenous embolism: an unusual cause of spinal cord infarction.

A 14-year-old girl experienced sudden onset of weakness progressing rapidly to paralysis. She died 7 days later from a massive pulmonary thromboembolus. Autopsy revealed extensive infarction of the spinal cord with a fibrocartilaginous embolus of the corresponding segment of the anterior spinal artery.

Giant cell arteritis in association with cerebral amyloid angiopathy: immunohistochemical and molecular studies.

Giant cell arteritis (GCA) usually manifests as a transmural vascular infiltrate of mononuclear and multinucleated giant cells (MNGC). We describe six patients with GCA associated with severe cerebral amyloid angiopathy (CAA), all with cerebral hemorrhage or varying degrees of cerebral infarct, and histological evidence of Alzheimer's disease (cortical CAA often predominating over senile plaques and neurofibrillary tangles). One case showed mostly cortical involvement (with old microhemorrhages), and the others were primarily leptomeningeal (with involvement of the underlying cortex and extensive encephalomalacia of adjacent brain). Many vessels with CAA exhibited a pronounced adventitial and perivascular infiltrate of lymphocytes, histiocytes, and MNGC. Immunohistochemical staining showed deposition of beta/A4 peptide primarily in the thickened media of CAA vessels, and within the cytoplasm of MNGC--suggesting phagocytosis of insoluble peptide. Cystatin C antibody stained vascular amyloid and diffusely highlighted astrocytic and MNGC cytoplasm. HAM56-positive macrophages were frequently seen around amyloid-laden vessels. Anti-smooth muscle actin immunohistochemistry suggests the occurrence of medial destruction by amyloid, with relative preservation of intimal cells. Ultrastructural studies performed in one case confirmed the presence of intracytoplasmic amyloid in MNGC. The GCA seen in these cases of CAA most likely represents a foreign body response to amyloid proteins, causing secondary destruction of the vessel wall. DNA from brain tissues of five affected patients was examined to assess whether mutations were present in exon 17 of the APP gene or exon 2 of the cystatin C gene, a finding that might explain the foreign body giant cell response to amyloid proteins in these cases. However, restriction fragment mapping of amplified gene segments showed that previously described mutations were not present in these cases.

Effects of stimulation and inhibition of protein kinase C on the cytosolic calcium concentration in rabbit afferent arterioles.

The effect of the protein kinase C (PKC) inhibitor chelerytrine (Ch) and the PKC activator 12-0-tetradecanoyl-phorbol-13-acetate (TPA) on the cytosolic calcium concentration ([Ca2+]i) in isolated intact rabbit afferent arterioles was investigated. [Ca2+]i was measured in the proximal and distal parts of the arteriole. Administration of 1 microM Ch gave rise to a peak followed by an elevated level of [Ca2+]i in both these parts. Neither the peak nor the elevated level of [Ca2+]i was significantly reduced by 1 microM nifedipine. The relative peak increase in [Ca2+]i in response to 1 microM noradrenaline (NA) or to 10 nM angiotensin II (AII) was significantly blunted in both parts after preincubation with 1 microM Ch. Depolarization with 25 mM K+ increased [Ca2+]i in both parts. Preincubation with Ch did not affect the increase in [Ca2+]i induced by 25 mM K+. TPA (10 and 100 nM) did not significantly affect the basal [Ca2+]i in the afferent arteriole. The [Ca2+]i response to NA or 25 mM K+ was not affected by TPA. We conclude that blockade of PKC increases [Ca2+]i in afferent arteriolar smooth muscle by a mechanism independent of L-type voltage-sensitive calcium channels. Inhibition of PKC blunts the relative increase in [Ca2+]i in response to AII and, to a lesser extent, that induced by NA. We conclude that PKC might be important in modulating the calcium changes that occur in response to these vasoconstrictors.