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[Diagnosis of endolymphatic hydrops using low frequency modulated distortion product otoacoustic emissions].

BACKGROUND: The low frequency modulation of distortion product otoacoustic emissions (DPOAEs) is an objective audiometric method that appears to be a useful tool for the diagnosis of endolymphatic hydrops (EH), e.g. in patients with Menière's disease, or in those who present only some of the symptoms of the disease. METHOD: Low-frequency modulated DPOAEs were registered in 20 patients with unilateral Menière's disease (13 women and 7 men, aged 40-66 years) and were compared to a control group matched in age and gender. As a diagnostic parameter, the 'modulation index' MI=1/2 MS/DM was used (MS or modulation span, being the difference between the maximal and the minimal DPOAE-amplitude, and DM, being the mean of the suppressed stationary DPOAE-amplitude). RESULTS: In the patients with unilateral Menière's disease, MI was lower than in the control group. This difference was highly significant. In 56% of the patients' contralateral ears MI was lower than the cut off-value and significantly lower than in the control group, but did not differ significantly from the patients' ipsilateral ears. CONCLUSION: The registration of low-frequency modulated DPOAEs is comparable to the generally applied transtympanic electrocochleography in its diagnostic validity. The method is fast and non-invasive and could be applied to monitor the course of the disease.

Acoustic Stimulation↗

[Dependence of "amplitude modulation following response" on attention].

BACKGROUND AND OBJECTIVE: Amplitude modulation following responses (AMFR) allows good estimation of the hearing threshold due to the very narrow band excitation of the cochlea. Audiological use of AMFR requires knowledge of the relationship of these responses to the state of vigilance. The few studies published compared only qualitatively the amplitude of AMFR recorded in awake subjects to that recorded in sleeping subjects. A quantitative determination of the level of vigilance on the basis of recorded physiological parameters has not yet been carried out. In the present study, the relationship between the amplitude of AMFR and the level of vigilance was investigated quantitatively. PATIENTS/METHODS: In eight adults with normal hearing, the relationship between the AMFR amplitude and EEG amplitude in the delta- and theta-band was determined. The amplitude in both frequency bands was used to indicate the state of vigilance. The subjects were studied during natural and drug-induced sleep. A 1-kHz carrier tone with a sinusoidally modulated amplitude of 40 Hz or 80 Hz was used as stimulus. RESULTS: At 40-Hz modulation frequency, the AMFR amplitude correlates with the EEG amplitude both in natural and drug-induced sleep. An increase in EEG activity is paralleled by a significant reduction of AMFR amplitude. At 80-Hz modulation frequency, no relationship between AMFR amplitude and EEG activity could be detected. Under all conditions, the amplitudes of AMFR evoked by a modulation frequency of 80 Hz were significantly lower than those evoked by 40 Hz. CONCLUSIONS: These results suggest that for an audiological use of the 40-Hz AMFR the state of vigilance should be stabilised at a constantly high level. In spite of the lower influence of vigilance on the 80-Hz AMFR, this response appears less ideal for threshold estimation in adults due to the significantly smaller amplitudes.

Adult↗

Role of basolateral amygdala dopamine in modulating prepulse inhibition and latent inhibition in the rat.

RATIONALE: The dopamine (DA) projection to the basolateral amygdala (BLA) modulates nucleus accumbens (NAc) and medial prefrontal cortex (mPFC) DA transmission. Given the involvement of the BLA, and of NAc and mPFC DA, in select forms of information processing, we sought to determine the role of BLA DA in modulating prepulse inhibition (PPI) and latent inhibition (LI). OBJECTIVE: The effects of BLA D1 (SCH 23390) and D2/D3 (raclopride) receptor blockade on PPI and LI were examined. METHODS: Separate groups of male Long-Evans rats received bilateral intra-BLA infusions of SCH 23390 (3.2 or 6.4 microg/0.5 microl per side), raclopride (2.5 or 5.0 microg/0.5 microl per side) or saline prior to testing. In two experiments, the effects of BLA DA receptor antagonism on PPI of the acoustic startle response (ASR) and LI of conditioned taste aversion were determined. A control group received bilateral intra-striatal infusions of SCH 23390 or raclopride prior to PPI testing. RESULTS: Intra-BLA SCH 23390 or raclopride had no effect on the ASR. Intra-BLA SCH 23390 enhanced and raclopride disrupted PPI, both in a dose-related manner. Intra-striatal SCH 23390 or raclopride had no effect on PPI or ASR magnitude. Finally, BLA DA receptor blockade had no effect on LI. CONCLUSIONS: These results indicate that PPI is modulated by BLA DA and suggest that this modulation occurs independently of changes in NAc and/or mPFC DA transmission. They also suggest that BLA DA is not involved in modulating LI and add to evidence indicating that PPI and LI are mediated by different neural substrates.

Amygdala↗

Modulation techniques and applications in comprehensive two-dimensional gas chromatography (GC x GC).

More than a decade after Phillips' first published work this article reviews recent developments in comprehensive two-dimensional gas chromatography (GC x GC). Special attention is devoted to the further development and diversity of modulation devices. These include heated sweepers, cryofocused modulators, and a variety of diaphragm valve-switching strategies. It is demonstrated that all modulation approaches can be very well suited to GC x GC, depending on the particular application. Diaphragm-valve modulation is very powerful for volatile organic compounds. Slotted heater and cryofocused modulation are preferred for samples that contain non-volatile components. Applications ranging from petroleum to environmental and biological samples are illustrated. Extension of the technique to GC x GC-mass spectrometry (MS) is also discussed and trends for future research activity are pointed out.

Chromatography, Gas↗

Coordinated modulation of locomotor muscle synergies constructs straight-ahead and curvilinear walking in humans.

We describe the muscle synergies accompanying steering of walking along curved trajectories, in order to analyze the simultaneous control of progression and balance-threatening emerging forces. For this purpose, we bilaterally recorded in ten subjects the electromyograms (EMGs) of a representative sample of leg and trunk muscles (n=16) during continuous walking along one straight and two curved trajectories at natural speed. Curvilinear locomotion involved a graded, limb-dependent modulation of amplitude and timing of activity of the muscles of the legs and trunk. The turn-related modulation of the motor pattern was highly coordinated amongst muscles and body sides. For all muscles, linear relationships were detected between the spatial and temporal features of muscle EMG activity. The largest modulation of EMG was observed in gastrocnemius medialis and lateralis muscles, which showed opposite changes in timing and amplitude during curve-walking. Moreover, amplitude and timing characteristics of muscle activities were significantly correlated with the spatial and temporal gait adaptations that are associated with curvilinear locomotion. The present results reveal that fine-modulation of the muscle synergies underlying straight-ahead locomotion is enough to generate the adequate propulsive forces to steer walking and maintain balance. These findings suggest that the turn-related command operates by modulation of the phase relationships between the tightly coupled neuronal assemblies that drive motor neuron activity during walking. This would produce the invariant templates for locomotion kinematics that are at the base of human navigation in space.

Adult↗

Balancing bilateral sensory activity: callosal processing modulates sensory transmission through the contralateral thalamus by altering the response threshold.

Rats tactually explore a nearly spherical space field around their heads with their whiskers. The information sampled by the two sets of whiskers is integrated bilaterally at the cortical level in an activity dependent manner via the corpus callosum. We have recently shown that sensory activity in one barrel field cortex (BFC) modulates the processing of incoming sensory information to the other BFC. Whether interhemispheric integration is dynamically linked with corticothalamic modulation of incoming sensory activity is an important hypothesis to test, since subcortical relay neurons are directly modulated by cortical neurons through top-down processes. In the present study, we compared the direct sensory responses of single thalamic relay neurons under urethane anesthesia before and after inactivating the BFC contralateral to a thalamic neuron. The data show that silencing one BFC reduces response magnitude in contralateral thalamic relay neurons, significantly and reversibly, in response to test stimuli applied to the principal whisker at two times response threshold (2T) intensity for each unit. Neurons in the ventral posterior medial (VPM) nucleus and the medial division of the posterior nucleus (POm) react in a similar manner, although POm neurons are more profoundly depressed by inactivation of the contralateral BFC than VPM neurons. The results support the novel idea that the subcortical relay of sensory information to one hemisphere is strongly modulated by activity levels in the contralateral as well as in the ipsilateral SI cortex. The mechanism of the modulation appears to be based on shifting the stimulus-response curves of thalamic neurons, thereby rendering them more or less sensitive to sensory stimuli. We conclude that global sensory processing is created by combining activity in each cerebral hemisphere and continually balancing the flow of information to cortex by adjusting the responsiveness of ascending sensory pathways.

Action Potentials↗

Low-frequency common modulation of soleus motor unit discharge is enhanced during postural control in humans.

The maintenance of quiet stance requires the activation of muscles bilaterally. The soleus muscles in each leg share a common function in standing; that is, each muscle acts to control antero-posterior (AP) sway on its own side. We sought to determine the extent to which oscillations in motor unit discharge were related in motor unit pairs of the soleus muscles during postural and voluntary isometric tasks, both within and between legs. Subjects stood quietly for 5 min or performed a voluntary isometric plantarflexion contraction in a seated position. During the postural tasks, the excursions of AP sway between legs were highly correlated (rho = 0.86 +/- 0.06). The strength of common modulation of motor unit discharge rates was assessed using time- and frequency-domain analyses. The time-domain common drive analysis revealed that the strongest correlation in motor unit discharge modulation occurred in the postural task with unilateral pairs (rho = 0.71 +/- 0.13) being more strongly correlated than bilateral pairs (rho = 0.50 +/- 0.16). Common modulation of motor unit discharge was lowest for the voluntary tasks, with rho = 0.38 +/- 0.11 and 0.16 +/- 0.08 for unilateral and bilateral pairs, respectively. Similarly, the frequency-domain coherence analysis demonstrated an identical ordering effect, with the largest maximum pooled coherence occurring during standing posture in unilateral (0.070 at 1.6 Hz) and bilateral (0.055 at 1.6 Hz) recordings, whereas minimal coherence was observed in the voluntary task in both unilateral and bilateral recordings within the 0-5 Hz range. These results indicate that in the soleus muscle, common modulation of motor unit discharge is greater during postural tasks than during voluntary isometric tasks and can be observed in both bilateral and unilateral motor unit pairs. Differences in the extent of co-modulation of motor unit discharge between tasks may be attributed to either differences in the descending control or differences in the proprioceptive input between postural and isometric tasks.

Action Potentials↗

Basic response determinants of single neurons to amplitude modulation in the auditory midbrain.

Amplitude-modulated (AM) signals represent important components of environmental sounds. While single-cell responses to AM tones in the central auditory system were often studied using repetitive modulation, owing to its presence in vocalization signals, the AM response has not been fully depicted in terms of receptive field in the stimulus domain. This study was aimed to characterize the receptive field of AM response with respect to nonrepetitive AM stimuli and to understand how complex acoustic signals may be coded in the brain. A novel AM stimulus was implemented with a random envelope and a systemic change in intensity across trials. From 393 single units recorded in the inferior colliculus (IC) of urethane-anesthetized rats, responses to the AM stimulus were first characterized in terms of dot-raster pattern. Three types of response were identified: type I showing a monotonic response to mainly the steady states of the AM envelope and type II to rising phases of the AM envelope with a clear intensity preference. Type III showed a mixed response of both type I and type II. A small number of units, called type IV, responded to both rising and falling phases of the modulation. Using perispike averaging, the AM receptive field, or "level temporal receptive field" (LTRF), was displayed in a "stimulus level versus perispike time" plane. The LTRF, particularly of the type II response, clearly revealed triggering features of the cell. The triggering features are consistent with the representation of the cell's response in a receptive space formed by the Cartesian axes of the velocity of amplitude modulation, the intensity of the sound, and the range of modulation. We therefore considered these stimulus parameters as the three basic determinants of the AM response in the auditory midbrain.

Acoustic Stimulation↗

Modulation of human cutaneous reflexes during rhythmic cyclical arm movement.

The organization and pattern of cutaneous reflex modulation is unknown during rhythmic cyclical movements of the human upper limbs. On the assumption that these cyclic arm movements are central pattern generator (CPG) driven as has been suggested for leg movements such as walking, we hypothesized that cutaneous reflex amplitude would be independent of electromyographic (EMG) muscle activation level during rhythmic arm movement (phase-dependent modulation, as is often the case in the lower limb during locomotion). EMG was recorded from eight muscles crossing the human shoulder, elbow, and wrist joints while whole arm rhythmic cyclical movements were performed. Cutaneous reflexes were evoked with trains of electrical stimulation delivered at non-noxious intensities (approximately 2 x threshold for radiating paresthesia) to the superficial radial nerve innervating the lateral portion of the back of the hand. Phasic bursts of rhythmic muscle activity occurred throughout the movement cycle. Rhythmic EMG and kinematic patterns were similar to what has been seen in the human lower limb during locomotor activities such as cycling or walking: there were extensive periods of reciprocal activation of antagonist muscles. For most muscles, cutaneous reflexes were modulated with the movement cycle and were strongly correlated with the movement-related background EMG amplitude. It is concluded that cutaneous reflexes are primarily modulated by the background muscle activity during rhythmic human upper limb movements, with only some muscles showing phase-dependent modulation.

Adult↗

Tumor size and origin determine the antitumor activity of cisplatin or 5-fluorouracil and its modulation by leucovorin in murine colon carcinomas.

5-Fluorouracil (FUra) is one of the few effective agents in the treatment of patients with colorectal cancer. Its effects on the target enzyme thymidylate synthase (TS) can be modulated by leucovorin (LV) or cisplatin (CDDP). Tumor size and differentiation of tumor characteristics can influence therapeutic efficacy. We therefore studied the relationship between tumor size (cutoff point 200 mm3) and the antitumor activity of FUra and its modulation by LV in murine Colon 26 and Colon 38 tumors. The doubling time of tumors measuring > 200 mm3 was about 160% longer. The antitumor effect of FUra in these large tumors was decreased and could not be modulated by LV. In addition, three subtypes of Colon 26 (Colon 26-A, Colon 26-B, and Colon 26-10) were identified and characterized for tumor-induced weight loss, TS activity, response to chemotherapy, and histological features. Mice bearing Colon 38 and Colon 26-10 did not lose weight as a result of tumor growth. Colon 26-A caused a weight loss of up to 19%, whereas mice with Colon 26-B tumors remained within 10% of their initial weight and tolerated at least 2.5 times more tumor load than did mice bearing Colon 26-A, which induces cachexia. Among untreated tumors, TS catalytic activity was highest in Colon 26-B (5536 pmol mg protein(-1) h(-1)) and lowest in Colon 38 (799 pmol mg protein(-1) h(-1)); Colon 26-A and Colon 26-10 had intermediate activities (about 2500 pmol mg protein(-1) h(-1)). 5-Fluoro-2'-deoxyuridine monophosphate (FdUMP) binding was comparable in the three Colon 26 subtypes but was lower in Colon 38. The antitumor activity of FUra could be modulated by LV in Colon 38, Colon 26-10, and Colon 26-A but could not in Colon 26-B, with complete responses (CR) being obtained in Colon 26-10 and Colon 38. The latter two were highly sensitive to CDDP, followed by Colon 26-A and Colon 26-B (CRs: 50%, 40%, 25%, and 0, respectively). Furthermore, necrosis was noted in Colon 26-B and Colon 38 but not in Colon 26-A. In conclusion, (1) the antitumor activity of FUra in large tumors is decreased and cannot be modulated by LV and (2) characteristics and sensitivity to chemotherapeutics can vary substantially in closely related tumors of the same origin.

Adenocarcinoma↗

Temporal modulation transfer functions in the barn owl (Tyto alba).

Barn owls (Tyto alba) have evolved several specializations in their auditory system to achieve the high sensory acuity required for prey capture, including superior processing of interaural time differences and phase coding in the auditory periphery. Here, we tested whether barn owls are capable of high temporal resolution that may be a prerequisite for the accuracy in binaural processing. Temporal resolution was measured psychoacoustically and demonstrated in temporal modulation transfer functions. Four barn owls were trained in an operant task with food reward to detect sinusoidal amplitude modulations within an 800-ms gated white-noise burst or 800-ms periods of modulation in continuous white noise (spectrum levels of -5 dB and 15 dB SPL). Within the range of tested amplitude modulation frequencies from 5 Hz to 1280 Hz, barn owls' detection thresholds were lowest at 10-20 Hz. This sensitivity corresponds to an intensity-difference limen of between 0.9 dB and 1.4 dB. For all conditions, temporal modulation transfer functions showed band-pass characteristics with a high-frequency cutoff in the range of 37 Hz to 92 Hz, corresponding to minimum integration times of 4.3 ms and 1.7 ms, respectively. In summary, these data indicate a temporal resolution in the owl's auditory system that is good, but not unusual, compared to other vertebrates.

Animals↗

Field-specific responses in the auditory cortex of the unanaesthetized Mongolian gerbil to tones and slow frequency modulations.

Responses of multi-units in the auditory cortex (AC) of unanaesthetized Mongolian gerbils to pure tones and to linearly frequency modulated (FM) sounds were analysed. Three types of responses to pure tones could be clearly distinguished on the basis of spectral tuning properties, response latencies and overall temporal response pattern. In response to FM sweeps these three types discharged in a temporal pattern similar to tone responses. However, for all type-1 units the latencies of some phasic response components shifted systematically as a function of range and/or speed of modulation. Measurements of response latencies to FMs revealed that such responses were evoked whenever the modulation reached a particular instantaneous frequency (Fi). Effective Fi was: (1) independent of modulation range and speed, (2) always reached before the modulation arrived at a local maximum of the frequency response function (FRF) and consequently differed for downward and upward sweeps, and (3) was correlated with the steepest slope of that FRF maximum. The three different types of units were found in discrete and separate fields or regions of the AC. It is concluded that gross temporal response properties are one of the key features distinguishing auditory cortical regions in the Mongolian gerbil.

Acoustic Stimulation↗

[Long-term outcome of AV node modulation in 387 consecutive patients with AV nodal reentrant tachycardia].

UNLABELLED: Aim of this study was to assess the long-term results of AV-node modulation in patients with AV nodal reetrant tachycardia. METHODS: From December 1991 until September 1999, AV node modulation (ablation of the fast pathway or ablation/modification of the slow pathway) was performed in 387 consecutive patients with clinically apparent AV nodal reentrant tachycardia. Follow-up data was available in 95% of patients with a mean of 41 +/- 26 months after ablation. RESULTS: Acute success rate was 97%. During long-term follow-up recurrence rate was 7.4% without any difference between fast and slow pathway ablation. Recurrence occurred in 23% of patients with persistent dual AV node physiology after ablation (modification of the slow pathway) in contrast to 3% without dual AV node physiology (ablation of the slow pathway) (p = 0.002). The presence of a dual AV node physiology after slow pathway modulation was the only predictor of recurrence during long-term follow-up. The complication rate was 5.7%. The incidence of complete heart block was 1% without any difference between fast and slow pathway ablation. CONCLUSIONS: Catheter modulation of the AV node for the treatment of AV nodal reentrant tachycardia is effective and safe. During long-term follow-up, the recurrence rate was low. Modulation of the slow pathway is associated with a significantly higher recurrence rate than ablation of the slow pathway.

Adult↗

An explanation of contextual modulation by short-range isotropic connections and orientation map geometry in the primary visual cortex.

Recent experimental studies on the primary visual cortex have revealed complicated nonclassical neuronal activities. Contextual modulation on orientation-contrast is one typical example of nonclassical neuronal behavior. This modulation by surrounding stimuli in a nonclassical receptive field is mainly thought to be mediated by short- and long-range horizontal connections within the primary visual cortex. Short-range connections are circularly symmetrical and relatively independent of orientation preferences, while long-range connections are patchy, asymmetrical, and orientation specific. Although this modulation can be explained by long-range specific connections qualitatively, recent studies suggest that long-range connections alone may be insufficient with respect to the balance between two types of connections. Here, in order to clarify the role of short-range connections in the process of contextual modulation, we propose a model of the primary visual cortex with isotropic short-range connections and a geometric orientation map. Computational simulations using the model have demonstrated that contextual modulation can be explained by short-range connections alone. This is due to the interaction between the spatial periodicity of orientation domains and the excitatory-inhibitory regions arising from the propagation of activities.

Action Potentials↗

Cholinergic modulation of the cortical neuronal network.

Acetylcholine (ACh) is an important neurotransmitter of the CNS that binds both nicotinic and muscarinic receptors to exert its action. However, the mechanisms underlying the effects of cholinergic receptors have still not been completely elucidated. Central cholinergic neurons, mainly located in basal forebrain, send their projections to different structures including the cortex. The cortical innervation is diffuse and roughly topographic, which has prompted some authors to suspect a modulating role of ACh on the activity of the cortical network rather than a direct synaptic role. The cholinergic system is implicated in functional, behavioural and pathological states including cognitive function, nicotine addiction, Alzheimer's disease, Tourette's syndrome, epilepsies and schizophrenia. As these processes depend on the activation of glutamatergic and GABAergic systems, the cholinergic terminals must exert their effects via the modulation of excitatory and/or inhibitory neurotransmission. However, the understanding of cholinergic modulation is complex because it is the result of a mixture of positive and negative modulation, implying that there are various types, or even subtypes, of cholinergic receptors. In this review, we summarize the current knowledge on central cholinergic systems (projections and receptors) and then aim to focus on the implications for ACh in the modulation of cortical neuronal activity.

Acetylcholine↗

Modulation of fetal and adult acetylcholine receptors by Ca2+ and Mg2+ at developing mouse end-plates.

It has long been known that extracellular Ca2+ and Mg2+ modulate synaptic transmission at the neuromuscular junction, acting both pre- and post-synaptically. Relevant questions concerning the modulation of acetylcholine (ACh) receptors (AChRs) are however still open: are the fetal (gamma-AChR) and adult (epsilon-AChR) receptors modulated differently? Does the ACh concentration influence the effect of divalent cations? Is the effect on channel open duration dependent on type and concentration of divalent cation? These questions were addressed by studying the modulation of the single-channel behaviour of gamma- and epsilon-AChRs by Ca2+ and Mg2+ at the endplate of muscle fibres acutely dissociated from 12- to 14-day-old mice. Ca2+ reduced the conductances of the two receptor channels comparably. Mg2+ had a stronger effect than Ca2+ and reduced the conductance of epsilon-AChR significantly more than that of gamma-AChR. With 0.1 microM ACh, Ca2+ and Mg2+ increased the mean open duration of gamma- and epsilon-AChR channels comparably. At 100 microM ACh, gamma- and epsilon-AChR channels opened in bursts of strikingly similar duration, which was unaffected by divalent cations. These findings indicate that Ca2+, and even more so Mg2+, may regulate synaptic transmission by modulating the function of AChRs in addition to the well-established effects on transmitter release.

Animals↗

Differential modulation of Bordetella pertussis virulence genes as evidenced by DNA microarray analysis.

The production of most factors involved in Bordetella pertussis virulence is controlled by a two-component regulatory system termed BvgA/S. In the Bvg+ phase virulence-activated genes (vags) are expressed, and virulence-repressed genes (vrgs) are down-regulated. The expression of these genes can also be modulated by MgSO(4) or nicotinic acid. In this study we used microarrays to analyse the influence of BvgA/S or modulation on the expression of nearly 200 selected genes. With the exception of one vrg, all previously known vags and vrgs were correctly assigned as such, and the microarray analyses identified several new vags and vrgs, including genes coding for putative autotransporters, two-component systems, extracellular sigma factors, the adenylate cyclase accessory genes cyaBDE, and two genes coding for components of a type III secretion system. For most of the new vrgs and vags the results of the microarray analyses were confirmed by RT-PCR analysis and/or lacZfusions. The degree of regulation and modulation varied between genes, and showed a continuum from strongly BvgA/S-activated genes to strongly BvgA/S-repressed genes. The microarray analyses also led to the identification of a subset of vags and vrgs that are differentially regulated and modulated by MgSO(4) or nicotinic acid, indicating that these genes may be targets for multiple regulatory circuits. For example, the expression of bilA, a gene predicted to encode an intimin-like protein, was found to be activated by BvgA/S and up-modulated by nicotinic acid. Furthermore, surprisingly, in the strain analysed here, which produces only type 2 fimbriae, the fim3 gene was identified as a vrg, while fim2 was confirmed to be a vag.

Bordetella pertussis↗

Are non-modulating patients with essential hypertension a distinct subgroup? Implications for therapy.

In 40 to 50 percent of the essential hypertensive population, a high intake of sodium does not increase renal blood flow. These patients have been called "non-modulators" since their adrenal and renal vascular responses to angiotensin II are not modified by changes in sodium intake. To determine if these patients form a distinct subgroup, the frequency distribution of four characteristics that have been reported to be abnormal in non-modulators were analyzed: aldosterone secretory response to acute volume depletion, plasma aldosterone response to angiotensin II infusion, plasma renin activity response to saline infusion, and renal blood flow response to salt loading. All four characteristics had a bimodal distribution in patients with hypertension. The effect of angiotensin converting enzyme inhibition on two of these abnormalities was also reviewed. In both cases--aldosterone secretory response to angiotensin II and renal blood flow response to salt loading--converting enzyme inhibition restored the abnormal responses towards normal values in non-modulators without altering the responses in normotensives or modulators. Indeed, the correction of the abnormal renal blood flow response to salt loading through converting enzyme inhibition may explain how converting enzyme inhibitors normalize blood pressure in 50 percent of the patients in whom the renin-angiotensin system is suppressed by an unrestricted, typically high, intake of salt. In summary, non-modulators are a distinct subset of the hypertensive population. Converting enzyme inhibition corrects the abnormalities that may be responsible for their hypertensive condition and, therefore, may be a specific form of therapy for these patients.

Adrenal Glands↗