RESUMEN

BACKGROUND: Secondary prevention of coronary artery disease is effective in reducing morbitiy and mortality. Our aim was to assess lipid management following non-attendance to a hospital based secondary prevention clinic. METHODS: Data were collected over 5 years on statin usage and total cholesterol levels for patients with coronary artery disease following attendance at a cardiac nurse led outpatient clinic. Lipid levels were taken from a central laboratory database, for both patients discharged from clinic and non-attenders. RESULTS: From 935 inpatients discharged from hospital, 248 (29%) defaulted from outpatient follow up. Lipid lowering drug usage was similar (72% vs. 74% for non-attenders, p=NS). Attenders at the nurse led outpatient clinic were more likely to achieve a total cholesterol <5 mmol/L at discharge than non-attenders (70% vs. 43%; p < 0.001), with a lower mean total cholesterol (4.75 +/- 0.06 mmol/L vs. 5.33 +/- 0.08 mmol/L; p < 0.001). Non-attenders subsequently had a greater number of cholesterol measurements than those who were discharged from the hospital based clinic (range 0-12, c2 23.8 on 12 df p < 0.005). Lipid profiles in hospital non-attenders remained inferior with fewer achieving a total cholesterol <5 mmol/L (61% vs. 78%; p < 0.001), and having greater mean total cholesterol levels (4.85 +/- 0.06 mmol/L vs. 4.52 +/- 0.05 mmol/L; p < 0.001). CONCLUSIONS: Patients defaulting from hospital follow up have higher total cholesterols with fewer at target level compared to attenders. Though non-attenders receive subsequent lipid measurement, inferior lipid profiles persist compared to patients who completed hospital follow up to be discharged. Further implementation strategies are needed with regard to lipid management in this patient group.

Asunto(s)

Colesterol/sangre , Enfermedad de la Arteria Coronaria/tratamiento farmacológico , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Hiperlipidemias/prevención & control , Hipolipemiantes/uso terapéutico , Servicio Ambulatorio en Hospital/estadística & datos numéricos , Negativa del Paciente al Tratamiento/estadística & datos numéricos , Adulto , Anciano , Anciano de 80 o más Años , Enfermedad de la Arteria Coronaria/fisiopatología , Utilización de Medicamentos , Femenino , Humanos , Hiperlipidemias/tratamiento farmacológico , Entrevistas como Asunto , Lípidos/sangre , Masculino , Persona de Mediana Edad , Enfermeras Practicantes , Educación del Paciente como Asunto

RESUMEN

BACKGROUND: Secondary prevention of coronary artery disease is effective in reducing morbidity and mortality, but deficiencies in implementation and prescription bias have been identified. AIM: To assess progress in secondary prevention measures for coronary heart disease and whether there was a difference between patient subgroups with angina, post myocardial infarction or revascularization. DESIGN: Retrospective analysis. METHODS: Between 1997 and 2001, data were collected on prophylactic prescribing, demographic and lifestyle information, at baseline and 1 year following attendance at a hospital-based, cardiac-nurse-led out-patient clinic. RESULTS: Patients (n = 945) were entered into the database at hospital discharge and 619 (72%) attended at 1 year. Aspirin and statin prescribing increased, though ACE inhibitor use was less. Mean total cholesterol at baseline reduced to 4.92 +/- 0.11 mmol/l (p < 0.001) in 2000, with a further reduction to 4.59 +/- 0.08 mmol/l at the 1-year visit in 2001 (p < 0.001). The proportion of patients with total cholesterol < 5 mmol/l increased to 38% in 2000, reaching 70% in 2001. Smokers at baseline were similar at around 30%, although this had reduced to 10% in 2001 (p < 0.001). No change in weight was seen for patients with BMI >or=30 (p = NS). No significant differences were seen between patient subgroups (p = NS). DISCUSSION: Secondary prevention measures are improving, especially in prophylactic prescribing, lipid management and smoking cessation, although scope for further improvement remains. No difference was seen between the patient subgroups. Lifestyle measures need to be addressed to gain maximum benefit in addressing overall cardiovascular risk.

Asunto(s)

Enfermedad de la Arteria Coronaria/prevención & control , Anciano , Inhibidores de la Enzima Convertidora de Angiotensina/administración & dosificación , Aspirina/administración & dosificación , Colesterol/sangre , Utilización de Medicamentos , Estudios de Seguimiento , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/administración & dosificación , Persona de Mediana Edad , Servicio Ambulatorio en Hospital , Inhibidores de Agregación Plaquetaria/administración & dosificación , Estudios Retrospectivos , Cese del Hábito de Fumar/estadística & datos numéricos

RESUMEN

Pericardial cysts are rare mediastinal cysts, which are commonly asymptomatic. We report the case of a middle-aged lady, with a previous short history of chest pain, who was found to have a focal pericardial density, felt to have been a consequence of haemorrhage into such a cyst.

Asunto(s)

Dolor en el Pecho/etiología , Quiste Mediastínico/complicaciones , Femenino , Humanos , Quiste Mediastínico/diagnóstico por imagen , Persona de Mediana Edad , Tomografía Computarizada por Rayos X

RESUMEN

Sildenafil citrate (Viagra, Pfizer, Inc., New York, N.Y.) is widely prescribed as a treatment for male erectile dysfunction. It is metabolized predominantly by the cytochrome P450 3A4 hepatic microsomal isoenzyme and effects can, therefore, be potentiated by such inhibitors. The vasodilatory effects of Viagra necessitate caution in its use in patients with cardiovascular disease and it is contraindicated in patients receiving nitrates. Previous literature has drawn attention to Viagra use and myocardial infarction. This paper reports the case of a young man who presented with a myocardial infarction after taking Viagra in combination with cannabis, a known inhibitor of the cytochrome P450 3A4 isoenzyme.

Asunto(s)

Fumar Marihuana/efectos adversos , Infarto del Miocardio/inducido químicamente , Inhibidores de Fosfodiesterasa/efectos adversos , Piperazinas/efectos adversos , Adulto , Humanos , Masculino , Infarto del Miocardio/diagnóstico , Purinas , Citrato de Sildenafil , Sulfonas

Asunto(s)

Angioplastia Coronaria con Balón/métodos , Enfermedad Coronaria/terapia , Endosonografía , Stents , Angiografía Coronaria , Enfermedad Coronaria/diagnóstico por imagen , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto , Recurrencia

RESUMEN

BACKGROUND: The aim of the study was to establish the influence of proximal coronary artery atheroma and smoking habit on the stimulated release of tissue plasminogen activator (tPA) from the heart. METHODS AND RESULTS: After diagnostic coronary angiography in 25 patients, the left anterior descending coronary artery (LAD) was instrumented, and the proximal LAD plaque volume was determined by use of intravascular ultrasound (IVUS). Blood flow and fibrinolytic responses to selective LAD infusion of saline, substance P (10 to 40 pmol/min; endothelium-dependent), and sodium nitroprusside (5 to 20 microgram/min; endothelium-independent) were measured by intracoronary IVUS and Doppler, combined with arterial and coronary sinus blood sampling. Mean plaque burden was 5.5+/-0.8 mm(3)/mm vessel (range 0.6 to 13.7 mm(3)/mm vessel). LAD blood flow increased with both substance P and sodium nitroprusside (P<0.001), although coronary sinus plasma tPA antigen and activity concentrations increased only during substance P infusion (P<0.006 for both). There was a strong inverse correlation between the LAD plaque burden and release of active tPA (r=-0.61, P=0.003). Cigarette smoking was associated with impaired coronary release of active tPA (current smokers, 31+/-23 IU/min; ex-smokers, 50+/-33 IU/min; nonsmokers 202+/-73 IU/min; P<0.05). CONCLUSIONS: We found that both the coronary atheromatous plaque burden and smoking habit are associated with a reduced acute local fibrinolytic capacity of the heart. These important findings provide evidence of a direct link between endogenous fibrinolysis, endothelial dysfunction, and atherothrombosis in the coronary circulation and may explain the greater efficacy of thrombolytic therapy for myocardial infarction in cigarette smokers.

Asunto(s)

Enfermedad de la Arteria Coronaria/metabolismo , Trombosis Coronaria/etiología , Vasos Coronarios/enzimología , Endotelio Vascular/enzimología , Fumar/efectos adversos , Activador de Tejido Plasminógeno/metabolismo , Área Bajo la Curva , Velocidad del Flujo Sanguíneo/efectos de los fármacos , Cateterismo Cardíaco , Enfermedad de la Arteria Coronaria/complicaciones , Enfermedad de la Arteria Coronaria/diagnóstico , Enfermedad de la Arteria Coronaria/fisiopatología , Circulación Coronaria/efectos de los fármacos , Endosonografía , Endotelio Vascular/efectos de los fármacos , Endotelio Vascular/fisiopatología , Femenino , Humanos , Infusiones Intraarteriales , Masculino , Persona de Mediana Edad , Nitroprusiato/administración & dosificación , Inhibidor 1 de Activador Plasminogénico/sangre , Análisis de Regresión , Factores de Riesgo , Sustancia P/administración & dosificación , Vasodilatadores/administración & dosificación

RESUMEN

In transgenic mice expressing ectopic substance P fibres in the spinal white matter, a normally innocuous mechanical stimulus induces hyperalgesia and allodynia which are reversed by substance P and N-methyl-D-aspartate receptor antagonists. This period of enhanced excitation is followed by a rebound overshoot in these animals. As previous evidence indicates opioid mechanisms in a similar rebound in normal animals, the present study was done to determine the effects of systemic administration of morphine and the opiate receptor antagonist, naloxone, on the stimulus-induced responses in the tail withdrawal reflex. Once baseline reaction times had been taken, different combinations of saline, naloxone and morphine were administered intraperitoneally to transgenic and control mice of either sex. A mechanical conditioning stimulus of 450g was then applied to the tip of the tail for 2s. This stimulus was innocuous in control mice given saline or naloxone, but provoked a nociceptive response in transgenic mice given these compounds. In control and transgenic mice, following morphine administration there was an antinociceptive effect. In control mice the subsequent mechanical stimulus had no effect. However, in transgenic mice the mechanical stimulus produced a further antinociception. Naloxone blocked the effect of morphine and the subsequent conditioning stimulus in both control and transgenic mice. The results indicate that while morphine is equally effective on the withdrawal reflex in both types of animal, in the transgenic mice morphine reveals an intrinsic, naloxone-sensitive antinociceptive mechanism. The data are interpreted to suggest that over-expression of substance P or some other factor in the spinal cord of transgenic mice is associated with the up-regulation or facilitation of an opiate-mediated intrinsic antinociceptive mechanism. This is a novel observation because the genetic manipulation in this transgenic mouse results in a transient over-expression of nerve growth factor during development that leads to the formation of ectopic primary afferent fibres in the spinal cord containing substance P. These fibres persist indefinitely after the nerve growth factor levels return to normal. Opioid mechanisms, which are likely of dorsal horn origin, do not fall under the direct influence of nerve growth factor mechanisms and therefore the intriguing possibility is raised that opioid mechanisms in the spinal cord are regulated at least in part by substance P-related mechanisms.

Asunto(s)

Regulación de la Expresión Génica/efectos de los fármacos , Regulación de la Expresión Génica/fisiología , Nociceptores/efectos de los fármacos , Nociceptores/metabolismo , Péptidos Opioides/efectos de los fármacos , Péptidos Opioides/metabolismo , Dolor/tratamiento farmacológico , Dolor/fisiopatología , Médula Espinal/efectos de los fármacos , Médula Espinal/metabolismo , Sustancia P/efectos de los fármacos , Sustancia P/metabolismo , Regulación hacia Arriba/efectos de los fármacos , Regulación hacia Arriba/fisiología , Analgésicos Opioides/farmacología , Animales , Interacciones Farmacológicas , Femenino , Masculino , Ratones , Ratones Transgénicos , Morfina/farmacología , Naloxona/farmacología , Antagonistas de Narcóticos/farmacología , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Nociceptores/citología , Dimensión del Dolor/efectos de los fármacos , Tiempo de Reacción/efectos de los fármacos , Tiempo de Reacción/fisiología , Médula Espinal/citología

RESUMEN

Substance P and neurokinin B are tachykinins that derive from different precursors. Both tachykinins are known to be involved in the processing of pain-related information. Initial studies suggested an antinociceptive effect for neurokinin B, but more recent data indicate that neurokinin B facilitates nociception. Unfortunately, morphologic correlates are lacking, as little is known about the distribution of neurokinin B, especially at the ultrastructural level. Because of its potentially important role in the processing of pain-related information, we decided to investigate the synaptic interactions of neurokinin B-immunoreactive profiles in laminae I-III of the rat cervical spinal dorsal horn and their relation to substance P-immunoreactive structures. An antibody raised against a portion of the neurokinin B precursor peptide was used for the detection of neurokinin B. Neurokinin B-like immunoreactivity occurred in all superficial laminae, with the highest density in inner lamina II and the lowest in lamina III. Neurokinin B-like immunoreactive axonal boutons were mainly dome-shaped and established symmetric synaptic contacts with dendrites or cell bodies. Neurokinin B-like immunoreactivity was also detected in dendritic profiles in all superficial laminae. Some of these dendritic profiles were part of synaptic glomeruli in inner lamina II and lamina III. Double-labeling for neurokinin B and substance P showed a lack of appositions and synapses between neurokinin B and substance P-positive profiles. Furthermore, very few profiles double-labeled for the two peptides were observed. Double-labeling for gamma-aminobutyric acid (GABA) and neurokinin B showed a complete absence of neurokinin B/GABA co-localization. Furthermore, neurokinin B-positive profiles were never presynaptic to GABA-immunoreactive profiles, but frequently neurokinin B-positive dendrites were postsynaptic to GABA-immunoreactive boutons. These results suggest that neurokinin B participates in circuits separate from those involving substance P, as virtually no anatomic correlation was found between the two neuropeptides.

Asunto(s)

Neuroquinina B/análisis , Células del Asta Posterior/metabolismo , Sustancia P/análisis , Ácido gamma-Aminobutírico/análisis , Animales , Axones/metabolismo , Axones/ultraestructura , Inmunohistoquímica , Masculino , Microscopía Electrónica , Nociceptores/metabolismo , Nociceptores/ultraestructura , Dolor/metabolismo , Células del Asta Posterior/ultraestructura , Ratas , Ratas Wistar

RESUMEN

A recent immunocytochemical study has shown that substance P (SP) preferentially innervates targets expressing the neurokinin-1 receptor (NK-1r) in the superficial spinal dorsal horn of the rat. Based on these findings, we decided to further investigate the relationship between SP and the NK-1r in a transgenic mouse model in which SP fibres are ectopically located. Double-labelling immunocytochemistry at both the light and electron microscopic levels was performed to study the association between SP and the NK-1r in the spinal white matter of both control and transgenic mice. Light microscopy revealed NK-1r-immunoreactive (IR) dendrites in the white matter of the dorsolateral funiculus in both control and transgenic mice. In transgenic mice, but not in controls, SP-IR fibres were observed in close proximity to the NK-1r-IR dendrites in the white matter. At the ultrastructural level, SP-IR boutons were apposed to NK-1r-IR dendrites in the dorsolateral funiculus of transgenic mice, and a synapse was frequently observed as well. These results indicate that, even in conditions in which SP fibres are ectopically located, they still preferentially innervate targets expressing the NK-1r.

Asunto(s)

Dendritas/química , Receptores de Neuroquinina-2/análisis , Receptores Presinapticos/análisis , Médula Espinal/química , Sustancia P/análisis , Animales , Inmunohistoquímica , Masculino , Ratones , Ratones Transgénicos , Microscopía Electrónica , Fibras Nerviosas/química , Médula Espinal/ultraestructura

RESUMEN

A transgenic mouse has been developed which, during development, over-expresses nerve growth factor under the control of a myelin basic protein promoter. These animals display an ectopic network of substance P-containing sensory fibers in the white matter of the spinal cord. To study the functional significance of this model to nociception, these mice were studied in a test measuring the latency to tail withdrawal from a noxious radiant heat stimulus. Baseline reaction times were significantly less in transgenic mice, suggesting thermal allodynia. A mechanical stimulus was then applied to the tip of the tail at either 450 g or 1400 g for 2 s and tail withdrawal readings were taken for another 10 min. In control mice, the 450 g stimulus was without effect, suggesting that it is normally innocuous. In transgenic mice, this stimulus induced a transient decrease in withdrawal latency at 1 min. Thus, transgenic mice exhibited mechanical allodynia. The 1400 g stimulus decreased withdrawal latency in both transgenic and control mice. However, the response was greater in transgenic mice, indicating that they exhibited mechanical hyperalgesia. The neurokinin-1 receptor antagonist CP-96,345, but not the inactive stereoisomer CP-96,344, administered subcutaneously 30 min before the 450 g stimulus, blocked the stimulation-induced allodynia in transgenic mice, and revealed a transient antinociception in transgenic and control mice. Ketamine, an N-methyl-D-aspartate receptor antagonist, given intraperitoneally 10 min before 450 g stimulation, blocked the allodynia in transgenic mice. These results indicate that these transgenic mice display hyperalgesia and allodynia, and that these nociceptive responses are reversed by substance P and N-methyl-D-aspartate receptor antagonists.

Asunto(s)

Analgésicos/uso terapéutico , Compuestos de Bifenilo/uso terapéutico , Antagonistas de Aminoácidos Excitadores/uso terapéutico , Hiperalgesia/etiología , Ketamina/uso terapéutico , Antagonistas del Receptor de Neuroquinina-1 , Nociceptores/efectos de los fármacos , Receptores de N-Metil-D-Aspartato/antagonistas & inhibidores , Sustancia P/fisiología , Analgésicos/farmacología , Animales , Compuestos de Bifenilo/farmacología , Antagonistas de Aminoácidos Excitadores/farmacología , Regulación de la Expresión Génica , Calor/efectos adversos , Hiperalgesia/tratamiento farmacológico , Ketamina/farmacología , Masculino , Ratones , Ratones Transgénicos , Proteína Básica de Mielina/genética , Nociceptores/fisiología , Regiones Promotoras Genéticas , Tiempo de Reacción/efectos de los fármacos , Proteínas Recombinantes de Fusión/fisiología , Médula Espinal/metabolismo , Médula Espinal/fisiopatología , Estrés Mecánico , Sustancia P/biosíntesis , Sustancia P/genética

RESUMEN

Substance P plays an important role in the transmission of pain-related information in the dorsal horn of the spinal cord. Recent immunocytochemical studies have shown a mismatch between the distribution of substance P and its receptor in the superficial laminae of the dorsal horn. Because such a mismatch was not observed by using classical radioligand binding studies, we decided to investigate further the issue of the relationship between substance P and its receptor by using an antibody raised against a portion of the carboxyl terminal of the neurokinin 1 receptor and a bispecific monoclonal antibodies against substance P and horseradish peroxidase. Light microscopy revealed a good correlation between the distributions of substance P and the neurokinin 1 receptor, both being localized with highest densities in lamina I and outer lamina II of the spinal dorsal horn. An ultrastructural double-labeling study, combining preembedding immunogold with enzyme-based immunocytochemistry, showed that most neurokinin 1 receptor immunoreactive dendrites were apposed by substance P containing boutons. A detailed quantitative analysis revealed that neurokinin 1 receptor immunoreactive dendrites received more appositions and synapses from substance P immunoreactive terminals than those not expressing the neurokinin 1 receptor. Such preferential innervation by substance P occurred in all superficial dorsal horn laminae even though neurokinin 1 receptor immunoreactive dendrites were a minority of the total number of dendritic profiles in the above laminae. These results suggest that, contrary to the belief that neuropeptides act in a diffuse manner at a considerable distance from their sites of release, substance P should act on profiles expressing the neurokinin 1 receptor at a short distance from its site of release.

Asunto(s)

Axones/fisiología , Dendritas/fisiología , Neuronas/fisiología , Receptores de Neuroquinina-1/fisiología , Médula Espinal/fisiología , Sustancia P/fisiología , Sinapsis/fisiología , Vías Aferentes , Animales , Axones/ultraestructura , Dendritas/ultraestructura , Inmunohistoquímica , Masculino , Microscopía Electrónica , Modelos Neurológicos , Neuronas/citología , Ratas , Ratas Wistar , Receptores de Neuroquinina-1/análisis , Médula Espinal/citología , Sustancia P/análisis , Sinapsis/ultraestructura , Tálamo/fisiología

RESUMEN

The benefits of continuous positive airway pressure (CPAP) therapy in patients with the sleep apnea/hypopnea syndrome (SAHS) are poorly documented and patients use CPAP less than physicians recommend. To establish patients' perceptions of benefit from CPAP and to identify determinants of CPAP use, 204 CPAP users completed a questionnaire relating to use of CPAP therapy, sleepiness, and road traffic incident rate before and after CPAP, perceived change in daytime function and nocturnal symptoms with treatment, and problems with CPAP. Variables from these domains of interest were examined, reduced through principal components analysis and correlated to assess associations between these and polysomnographic measures of illness severity. Self-reported CPAP use averaged 5.8 +/- SD 2 h a night. Subjective sleepiness rated by the Epworth sleepiness scale and road traffic incident rate were significantly reduced by CPAP (p<0.0001). A broad range of function and symptom items were highly significantly improved with CPAP (p<0.0001), corroborating the cost to community and industry from SAHS and the preventive value of CPAP. Road traffic incident rate before treatment was correlated with pre-CPAP sleepiness and SAHS severity. Subjective CPAP use correlated with sleepiness before treatment but not with SAHS severity. CPAP mask problems and side effects were not associated with reduced CPAP use, but "nuisance" complaints of awakenings, noise, and sore eyes from CPAP correlated negatively with reported use. Greater reported CPAP use was associated with better resolution of sleepiness and greater improvement in daytime function and nocturnal symptoms.

Asunto(s)

Cooperación del Paciente , Respiración con Presión Positiva , Síndromes de la Apnea del Sueño/terapia , Accidentes de Tránsito , Femenino , Humanos , Masculino , Persona de Mediana Edad , Polisomnografía , Síndromes de la Apnea del Sueño/fisiopatología , Fases del Sueño , Encuestas y Cuestionarios

RESUMEN

The present study describes a novel renal hypertensive guinea pig model for comparing different inhibitors of the renin-angiotensin system (RAS). Renal hypertension was induced by a two-step procedure consisting of ligation of the left caudal renal artery and right nephrectomy. Sham-operated animals were used as controls. Arterial blood pressure and heart rate were monitored in conscious animals. Left caudal renal artery ligation and subsequent right nephrectomy led to a significant increase (32% over sham-operated controls, p < .05) in mean arterial blood pressure (MABP), 3 to 4 weeks following surgery. Renal hypertensive animals had increased urine production (from 63 +/- 8 mL/kg per day to 143 +/- 29 mL/kg per day, p < .05) and an increased incidence of proteinuria (11/13 animals had urine protein levels higher than 20 mg/kg per day). Five of the 13 renal hypertensive animals also had hematuria. On autopsy, an 83% increase in the left kidney/body weight ratio and a 37% increase in the heart/body weight ratio were observed in the renal hypertensive animals, compared to the sham-operated controls. Changes in blood pressure and heart rate were assessed before and after an intravenous bolus injection of the drug to be tested. Captopril reduced MABP in both sham-operated and renal hypertensive animals with equal efficacy (up to a maximum of 42%). In contrast, BILA 2157 BS, one of our human renin inhibitors, produced a similar maximum MABP decrease but only in renal hypertensive animals. This selective antihypertensive effect was also observed with enalkiren, another renin inhibitor. These results indicate that the renal hypertensive guinea pig is an useful model for comparing and contrasting different RAS inhibitors.

Asunto(s)

Modelos Animales de Enfermedad , Hipertensión Renal , Sistema Renina-Angiotensina/efectos de los fármacos , Animales , Antihipertensivos/farmacología , Presión Sanguínea/efectos de los fármacos , Captopril/farmacología , Dipéptidos/farmacología , Cobayas , Frecuencia Cardíaca/efectos de los fármacos , Hipertensión Renal/tratamiento farmacológico , Hipertensión Renal/etiología , Masculino , Piridinas/farmacología , Renina/antagonistas & inhibidores , Renina/farmacología , Tiazoles/farmacología

RESUMEN

The present study compares the hemodynamic effects and mechanisms of action of angiotensin II (AngII) antagonists, angiotensin converting enzyme (ACE) inhibitors, and renin inhibitors in the guinea pig, an animal with high similarity to primates in terms of in vitro and in vivo responses to several human renin inhibitors. Animals were anesthetized with urethane and ketamine. The carotid artery was catheterized for monitoring blood pressure and heart rate. After 30 min stabilization, drug (or vehicle) effects were monitored for 1 h following each increasing dose (i.v. bolus injection). Drugs tested include losartan, an AngII receptor antagonist; two renin inhibitors, BILA 2157 BS and PD-134672; and captopril, an ACE inhibitor. All drugs dose dependently decreased blood pressure. Diastolic blood pressure was reduced more than systolic blood pressure, suggestive of vasodilation. The maximum decrease (32 +/- 6%, p < 0.05 vs. vehicle) in mean arterial blood pressure (MABP) by losartan was achieved with a dose of 1 mg/kg. A similar decrease in MABP was observed with renin inhibitors at a dose of 3 mg/kg, without affecting heart rate. A further increase in the dose of renin inhibitors (6 mg/kg) decreased not only blood pressure but also heart rate. Captopril decreased MABP with a maximum of 48 +/- 3% (p < 0.05 vs. vehicle, losartan, and PD-134672). In the presence of HOE-140, a bradykinin antagonist, the MABP decrease by captopril was only 35 +/- 4%, (p < 0.05 vs. captopril alone). Bilateral nephrectomy reduced the peak MABP effect of PD-134672 by 67%, while the effects of captopril on MABP were affected to a lesser degree (57%). Therefore, captopril remains more effective in reducing MABP (p < 0.05 vs. that of PD-134672). These results suggest that renin inhibitors and AngII antagonists act more specifically on the renin - angiotensin system cascade, while captopril acts partially by a bradykinin-dependent mechanism. The small animal model described provides a novel tool for the comparative pharmacologic assessment of different renin - angiotensin system inhibitors.

Asunto(s)

Antagonistas de Receptores de Angiotensina , Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Compuestos de Bifenilo/farmacología , Presión Sanguínea/efectos de los fármacos , Bradiquinina/antagonistas & inhibidores , Captopril/farmacología , Imidazoles/farmacología , Sistema Renina-Angiotensina/efectos de los fármacos , Tetrazoles/farmacología , Alanina/análogos & derivados , Alanina/farmacología , Animales , Bradiquinina/análogos & derivados , Bradiquinina/farmacología , Cobayas , Losartán , Masculino , Nefrectomía , Piridinas/farmacología , Renina/antagonistas & inhibidores , Tiazoles/farmacología