RESUMO
Patients suffering an acute ischemic stroke can be treated with intravenous thrombolysis in the absence of contraindications. A known onset time is a prerequisite as treatment, according to guidelines, has to be started within 4.5 hours. In patients awakening with a stroke, the last time they were seen without a neurological deficit is assumed to be the time of onset. Thus, despite of lack of contraindications on initial brain imaging, these patients are largely excluded from therapy. This review discusses the underlying pathophysiological, clinical, and radiological evidence surrounding wake-up stroke and its consequences for making treatment decisions.
Assuntos
Isquemia Encefálica/tratamento farmacológico , Sono , Acidente Vascular Cerebral/tratamento farmacológico , Terapia Trombolítica/métodos , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/etiologia , Humanos , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/etiologia , Terapia Trombolítica/efeitos adversosRESUMO
Patients who suffer acute ischaemic stroke can be treated with thrombolysis if therapy is initiated early. Radiological evaluation of the intracranial tissue before such therapy can be given is mandatory. In this review current radiological diagnostic strategies are discussed for this patient group. Beyond non-enhanced computed tomography (CT), the standard imaging method for many years, more sophisticated CT stroke protocols including CT angiography and CT perfusion have been developed, and additionally an increasing number of patients are examined with magnetic resonance imaging as the first imaging method used. Advantages and challenges of the different methods are discussed.
Assuntos
Isquemia Encefálica/diagnóstico por imagem , Acidente Vascular Cerebral/diagnóstico por imagem , Humanos , RadiografiaRESUMO
BACKGROUND AND PURPOSE: The direct bridging concept in acute stroke treatment combines intravenous thrombolysis (IVT) and endovascular treatment (EVT). The frequency and extent of reperfusion obtained already due to IVT were evaluated. Additionally undesired events and the clinical outcome were analysed. METHODS: Fifty-seven acute stroke patients treated with direct bridging were analysed for this study. The response to IVT was evaluated according to the modified Thrombolysis in Cerebral Infarction scale (m-TICI). IVT responders (m-TICI ≥2B in digital subtraction angiography) were compared with IVT non-responders (m-TICI <2B in digital subtraction angiography) with respect to clinical outcome and occurrence of undesired events. RESULTS: Fourteen patients (25%) got a change from TICI 0 to ≥2B due to IVT alone. There were otherwise no differences between the IVT responders and IVT non-responders. CONCLUSIONS: Intravenous thrombolysis pretreatment in the context of the bridging approach contributes substantially to revascularization.
Assuntos
Isquemia Encefálica/tratamento farmacológico , Circulação Cerebrovascular , Fibrinolíticos/farmacologia , Avaliação de Resultados em Cuidados de Saúde , Acidente Vascular Cerebral/tratamento farmacológico , Terapia Trombolítica/métodos , Ativador de Plasminogênio Tecidual/farmacologia , Idoso , Idoso de 80 Anos ou mais , Circulação Cerebrovascular/efeitos dos fármacos , Terapia Combinada , Procedimentos Endovasculares/métodos , Feminino , Fibrinolíticos/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Ativador de Plasminogênio Tecidual/administração & dosagemRESUMO
In vitro affinity for vascular 5HT2 and alpha receptors was determined for several compounds (spiperone, ketanserin, mianserin, trazodone, mepiprazole, benzoctamine, m-trifluoro-methylphenylpiperazine, m-chlorophenylpiperazine, and 1-(1-naphthyl)piperazine) known to interact with serotonin receptors. All compounds competitively inhibited 5HT2 and alpha receptors with differing degrees of selectively. Based on these observations, ketanserin, benzoctamine, and 1(1-naphthyl)piperazine were evaluated as antihypertensive agents in spontaneously hypertensive rats (SHR). Of these compounds, 1-(1-naphthyl)piperazine was a highly selective 5HT2 receptor antagonist with a ratio of 5HT2 to alpha receptor affinity of greater than 2000. The ratio of 5HT2 to alpha receptor affinity for ketanserin and benzoctamine was 63 and 16, respectively. However, the order of affinity toward 5HT2 receptors was ketanserin greater than 1-(1-naphthyl)piperazine greater than benzoctamine whereas the order of affinity toward alpha receptors was ketanserin greater than benzoctamine greater than 1-(1-naphthyl)piperazine. A similar order of potency toward both 5HT2 and alpha receptors was found in pithed SHR based on antagonism of the pressor response to serotonin and methoxamine, respectively. In the SHR, maximum blood pressure reduction at a dose of 10 mg/kg i.p. was approximately 65 and 30 mm Hg for ketanserin and benzoctamine, respectively; 1-(1-naphthyl)piperazine did not affect blood pressure. Thus, blood pressure reduction more closely paralleled the in vitro and in vivo potency of these agents toward vascular alpha rather than 5HT2 receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Pressão Sanguínea/efeitos dos fármacos , Antagonistas da Serotonina/farmacologia , Animais , Antracenos/farmacologia , Ketanserina , Masculino , Metoxamina/farmacologia , Piperidinas/farmacologia , Ratos , Ratos Endogâmicos , Receptores Adrenérgicos alfa/efeitos dos fármacosRESUMO
Prehypertensive rabbits with renal artery stenosis of 3 days' duration (one-kidney, one clip) are known to have increased pressor responses to norepinephrine and vasopressin; this pressor hyperresponsiveness is restored to normal by the angiotensin II (AII) antagonist, [ Sar1, Ile8 ] AII, even though plasma renin activity (PRA) and plasma AII concentrations are not elevated. In the present study, the cross-circulation of blood between conscious one-kidney, 3-day renal artery stenosis rabbits and conscious normal rabbits resulted in the transfer of pressor hyperresponsiveness to the normal rabbits, although both groups of rabbits had normal values for PRA. A similar cross-circulation of blood between one-kidney rabbits without renal artery stenosis and normal rabbits did not alter the pressor responsiveness of the normal rabbits to norepinephrine. It was concluded that a circulating humoral factor is involved in mediating pressor hyperresponsiveness in 3-day renal artery stenosis rabbits. To evaluate the interrelationship between AII and the hormonal hyperresponsiveness factor, an additional experiment was performed in which blood was cross-circulated between one-kidney, 3-day renal artery stenosis rabbits and normal rabbits, with the normal rabbits receiving [ Sar1, Ile8 ] AII immediately following cross-circulation. Administration of this AII antagonist to the normal rabbits prevented them from showing pressor hyperresponsiveness following the cross-circulation of blood. It is concluded that in this prehypertensive renal artery stenosis model the humoral hyperresponsiveness factor exerts its effect through AII mechanisms, rather than AII acting to increase the release or secretion of the hyperresponsiveness factor.
Assuntos
Pressão Sanguínea , Obstrução da Artéria Renal/sangue , Renina/sangue , 1-Sarcosina-8-Isoleucina Angiotensina II/farmacologia , Angiotensina II/antagonistas & inibidores , Angiotensina II/farmacologia , Animais , Pressão Sanguínea/efeitos dos fármacos , Circulação Cruzada , Masculino , Nefrectomia , Norepinefrina/farmacologia , Coelhos , Obstrução da Artéria Renal/fisiopatologiaRESUMO
To enhance the potency of 1,2-dibenzamidobenzene-derived inhibitors of factor Xa (fXa), an amidine substituent was incorporated on one of the benzoyl side chains to interact with Asp189 in the S1 specificity pocket. Lead molecule 1 was docked into the active site of fXa to facilitate inhibitor design. Subsequently, iterative SAR studies and molecular modeling led to a 1000-fold increase in fXa affinity and a refined model of the new inhibitors in the fXa active site. Strong support for the computational model was achieved through the acquisition of an X-ray crystal structure using thrombin as a surrogate protein. The amidines in this series show high levels of selectivity for the inhibition of fXa relative to other trypsin-like serine proteases. Furthermore, the fXa affinity of compounds in this series (K(ass) = 50-500 x 10(6) L/mol) translates effectively into both anticoagulant activity in vitro and antithrombotic activity in vivo.
Assuntos
Amidinas/síntese química , Anticoagulantes/síntese química , Inibidores Enzimáticos/síntese química , Inibidores do Fator Xa , Fibrinolíticos/síntese química , Amidinas/química , Amidinas/metabolismo , Amidinas/farmacologia , Animais , Anticoagulantes/química , Anticoagulantes/metabolismo , Anticoagulantes/farmacologia , Sítios de Ligação , Cristalografia por Raios X , Cães , Desenho de Fármacos , Inibidores Enzimáticos/química , Inibidores Enzimáticos/metabolismo , Inibidores Enzimáticos/farmacologia , Fator Xa/química , Fator Xa/metabolismo , Fibrinolíticos/química , Fibrinolíticos/metabolismo , Fibrinolíticos/farmacologia , Humanos , Técnicas In Vitro , Masculino , Modelos Moleculares , Tempo de Protrombina , Coelhos , Ratos , Ratos Sprague-Dawley , Relação Estrutura-Atividade , Trombina/química , Trombina/metabolismo , Trombose/tratamento farmacológicoRESUMO
Xylamidine and BW501C67 (alpha-anilino-N-2-m-chlorophenoxypropylacetamidine), serotonin antagonists that have been reported not to cross the blood-brain barrier, were compared to other serotonin antagonists: mianserin, ketanserin, metergoline and LY 53857. All six compounds were potent inhibitors of the binding of tritiated spiperone to 5HT2 receptors in rat frontal cortex membranes in vitro and were less potent inhibitors of the binding of tritiated serotonin to 5HT1 receptors in rat brain membranes. All were potent antagonists of the 5HT2 receptor-mediated contractile response to serotonin in the rat jugular vein in vitro. At doses of 0.1 and 0.3 mg/kg i.p., xylamidine and BW501C67 antagonized the pressor response to intravenously injected serotonin in pithed rats. In contrast, neither xylamidine nor BW501C67 at doses of 1 or 3 mg/kg i.p. antagonized the elevation of serum corticosterone concentration by quipazine in rats, although the other compounds antagonized this effect with ED50 values between 0.03 and 0.9 mg/kg. These data corroborate the previously reported antiserotonin activity of xylamidine and BW501C67. Since xylamidine and BW501C67 were potent antagonists of a peripheral serotonergic response in vivo, their inability to antagonize the elevation of serum corticosterone concentration by quipazine suggests that this effect results from activation of central serotonin receptors.
Assuntos
Amidinas/farmacologia , Receptores de Serotonina/efeitos dos fármacos , Antagonistas da Serotonina/farmacologia , Animais , Pressão Sanguínea/efeitos dos fármacos , Córtex Cerebral/metabolismo , Corticosterona/sangue , Estado de Descerebração , Técnicas In Vitro , Masculino , Músculo Liso Vascular/efeitos dos fármacos , Quipazina/farmacologia , Ensaio Radioligante , Ratos , Ratos Endogâmicos SHR , Ratos EndogâmicosRESUMO
The purposes of these studies were to produce a small animal model of arterial thrombosis for study of novel antithrombotic agents, to validate a simple temperature index of occlusive thrombosis, and to describe the composition of the thrombus. Small thermocouple transducers were fabricated from readily available materials. A thermocouple was inserted under a carotid artery of the anesthetized rat and vessel temperature was recorded continuously. Arterial injury was induced by FeCl3 solution applied topically to the artery above the thermocouple. To validate the relationship between thrombotic occlusion and vessel temperature, blood flow velocity, proximal to the injury, and temperature were recorded simultaneously. Temperature decreased rapidly when velocity averaged 24 +/- 12 percent of control and velocity did not differ from zero within 20 sec. In normal vessels, average flow velocity did not decrease significantly from control until a fixed stenosis decreased diameter by 78 percent. Average time to occlusion (TTO), signaled by the abrupt temperature inflection, ranged from 56 +/- 4 min to 14 +/- 1 min after 10 and 65 percent FeCl3 application respectively. Vessel segments were fixed at various times after FeCl3 exposure and examined by scanning electron microscopy. Endothelial damage was observed and was associated with thrombus composed of activated platelets, fibrin strands and entrapped erythrocytes. The results demonstrate that FeCl3 dose-dependently induced formation of an occlusive mixed thrombus that was indexed by monitoring the time between FeCl3 application and a rapid temperature decrease in the carotid artery of the rat.
Assuntos
Trombose das Artérias Carótidas/induzido quimicamente , Compostos Férricos , Animais , Temperatura Corporal , Trombose das Artérias Carótidas/patologia , Trombose das Artérias Carótidas/fisiopatologia , Cloretos , Modelos Animais de Doenças , Masculino , Microscopia Eletrônica de Varredura , Ratos , Ratos EndogâmicosRESUMO
Amesergide is an orally active ergoline amide, 5-HT2-receptor antagonist with a long duration of action. Since a major metabolite of amesergide is 4-hydroxyamesergide, we questioned whether the formation of this metabolite might contribute to the pharmacological activity and long duration of action observed after oral administration of amesergide. 4-Hydroxyamesergide was a potent 5-HT2-receptor antagonist with an affinity equal to or greater than amesergide under in-vitro conditions as measured by blockade of vascular 5-HT2 receptors, and 5-hydroxytryptamine (5-HT)-amplified ADP-induced rabbit platelet aggregation. Furthermore, 4-hydroxyamesergide, like amesergide, inhibited the pressor response to 5-HT after its intravenous administration to rats and was about 3-fold more potent than amesergide in this regard. 4-Hydroxyamesergide was also a potent inhibitor of vascular 5-HT2 receptors after oral administration to rats. After oral administration, 4-hydroxyamesergide had a similar or slightly greater duration of activity than the parent molecule. 4-Hydroxyamesergide, again like amesergide, also blocked central 5-HT2 receptors after its in-vivo administration to rats as measured by its ability to inhibit quipazine-induced increases in serum corticosterone. Thus, the formation of 4-hydroxyamesergide after oral administration of amesergide to animals and man may contribute to the potency and long duration of action of amesergide as a 5-HT2-receptor antagonist.
Assuntos
Ergolinas/farmacologia , Antagonistas da Serotonina/farmacologia , Difosfato de Adenosina/farmacologia , Animais , Pressão Sanguínea/efeitos dos fármacos , Corticosterona/sangue , Técnicas In Vitro , Masculino , Músculo Liso Vascular/efeitos dos fármacos , Agregação Plaquetária/efeitos dos fármacos , Quipazina/antagonistas & inibidores , Quipazina/farmacologia , Coelhos , Ensaio Radioligante , Ratos , Ratos Sprague-Dawley , Ratos Wistar , Receptores de Superfície Celular/efeitos dos fármacosRESUMO
OBJECTIVES: The understanding of stroke has changed in the recent years from rehabilitation to an emergency approach. We review existing data from symptom recognition to thrombolysis and identify challenges in the different phases of patient treatment. RESULTS: Implementation of treatment in dedicated stroke units with a multidisciplinary team exclusively treating stroke patients has led to significant reduction of stroke morbidity and mortality. Yet, first the introduction of treatment with intravenous rtPA (IVT) has led to the 'time is brain' concept where stroke is conceived as an emergency. As neuronal death in stroke is time dependent, all effort should be laid on immediate symptom recognition, rapid transport to the nearest hospital with a stroke treatment facility and diagnosis and treatment as soon as possible. The main cause of prehospital delay is that patients do not recognize that they suffered a stroke or out of other reasons do not call the Emergency Medical Services immediately. Educational stroke awareness campaigns may have an impact in increasing the number of patients eligible for rtPA treatment and can decrease the prehospital times if they are directed both to the public and to the medical divisions treating stroke. Stroke transport times can be shortened by the use of helicopter and a stroke mobile--an ambulance equipped with a CT scanner--may be helpful to decrease time from onset to treatment start in the future. Yet, IVT has several limitations such as a narrow time window and a weak effect in ischemic strokes caused by large vessel occlusions. In these cases, interventional procedures and the concept of bridging therapy, a combined approach of IVT and intraarterial thrombolysis or mechanical thrombectomy, might improve recanalization rates and patient outcome. CONCLUSIONS: As neuronal death in stroke patients occurs in a time-dependent fashion, all effort should be made to decrease time from symptom onset to treatment start with rtPA: major challenges are stroke recognition in the public, transport times to hospital and an efficient stroke triage in the hospital.
Assuntos
Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/terapia , Terapia Trombolítica/métodos , HumanosRESUMO
OBJECTIVES: Treatment of acute, ischemic stroke has changed markedly during the last two decades. We review existing data for optimizing modern stroke care. RESULTS: Implementation of stroke units, giving systematic treatment and observation to stroke patients, has lead to a significant reduction in death and dependency. Introduction of intravenous rt-PA (IVT) within 3 h for selected stroke patients and recent extension of the time window to 4.5 h improved the outcome even further. Still, one must consider that IVT has several limitations, such as a narrow time window and several contraindications, and the effect is modest, particularly in strokes with a large vessel occlusion. Recanalization of the occluded vessel is a major predictor for good outcome and should be set as a goal. Intra-arterial rt-PA (IAT) and the concept of bridging therapy (IVT prior to IAT or thrombectomy with a mechanical device) may improve recanalization rates and outcome. Randomized controlled trials (RCT) are available for IAT, but not for thrombectomy with devices, and we mostly have retrospective non-controlled data. The Merci- and Penumbra system are the most studied devices, for which recent studies report acceptable safety and efficacy. CONCLUSIONS: Sufficiently powered RCTs to evaluate the effect of thrombectomy with mechanical devices are warranted, but as the natural course of a large vessel stroke carries a devastating prognosis, a proactive recanalization approach is justified based on today's knowledge.
Assuntos
Isquemia Encefálica/terapia , Acidente Vascular Cerebral/terapia , Terapia Trombolítica/métodos , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/cirurgia , Fibrinolíticos/uso terapêutico , Humanos , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/cirurgia , Trombectomia , Fatores de Tempo , Ativador de Plasminogênio Tecidual/uso terapêutico , Resultado do TratamentoAssuntos
Anticoagulantes/farmacologia , Benzamidas/farmacologia , Derivados de Benzeno/farmacologia , Inibidores do Fator Xa , Fibrinolíticos/farmacologia , Animais , Anticoagulantes/química , Anticoagulantes/uso terapêutico , Benzamidas/química , Benzamidas/uso terapêutico , Derivados de Benzeno/química , Derivados de Benzeno/uso terapêutico , Modelos Animais de Doenças , Fator Xa/metabolismo , Fibrinolíticos/química , Fibrinolíticos/uso terapêutico , Humanos , Piperidinas/química , Coelhos , Relação Estrutura-Atividade , Trombose/prevenção & controleAssuntos
Inibidores da Enzima Conversora de Angiotensina , Captopril/administração & dosagem , Dipeptídeos/administração & dosagem , Hipertensão/tratamento farmacológico , Prolina/análogos & derivados , Administração Oral , Animais , Vasos Sanguíneos/enzimologia , Enalapril , Hipertensão/enzimologia , Masculino , Ratos , Fatores de TempoAssuntos
Carcinoma de Células Renais/diagnóstico , Neoplasias Renais/diagnóstico , Veias Renais , Trombose Venosa/diagnóstico , Angiografia Digital , Diagnóstico Diferencial , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X , Trombose Venosa/diagnóstico por imagemAssuntos
Sistema Justaglomerular/enzimologia , Renina/metabolismo , Animais , Ácidos Araquidônicos/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Denervação , Cães , Furosemida/farmacologia , Frequência Cardíaca , Indometacina/farmacologia , Rim/inervação , Neurônios/fisiologia , Pressorreceptores/fisiologia , Propranolol/farmacologia , Prostaglandinas/metabolismo , Reflexo , Fluxo Sanguíneo Regional/efeitos dos fármacos , Renina/sangueRESUMO
PURPOSE: Postrenal reasons of renal transplant failure can be assessed by magnetic resonance urography. This study was designed to retrospectively compare the diagnostic accuracy of static fluid (T2-)MRU compared to contrast enhanced (CE-)MRU in patients with renal transplant failure. MATERIAL AND METHODS: Thirty-five consecutive patients (14 female, 21 men; mean age 48.6 years) with renal transplant failure and sonographically detected hydronephrosis were examined both with T2-MRU as well as CE-MRU resulting in 39 MRU examinations. MRU was performed both using T2-weighted HASTE-sequence (T2-MRU) as well as Gadolinium-enhanced 3D-FLASH-sequence (CE-MRU) on a 1.5-T clinical MRI scanner (Magnetom Vision, Siemens Medical Solutions). Subjective image quality of resulting maximum intensity projection was assessed in consensus by two readers blinded to the final diagnosis, using a five point scale. MRU findings were correlated to sonography, operative results or clinical follow up. RESULTS: CE-MRU yielded a sensitivity of 85.7% (T2-MRU 76.2%), and a specificity of 83.3% (T2-MRU: 73.7%), however statistical significance was not reached. The subjective image quality was significantly better in CE-MRU. CONCLUSIONS: Only concerning subjective image quality CE-MRU proved superior to T2-MRU. Yet, there was no significant difference in diagnostic accuracy between T2- and CE-MRU. Thinking of incipient nephrogenic systemic fibrosis, T2-MRU can be used as reliable alternative in patients with decreased renal transplant function due to urological complications.
Assuntos
Gadolínio DTPA , Hidronefrose/diagnóstico , Hidronefrose/etiologia , Aumento da Imagem/métodos , Transplante de Rim/efeitos adversos , Transplante de Rim/patologia , Imageamento por Ressonância Magnética/métodos , Meios de Contraste , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Urografia/métodosRESUMO
OBJECTIVE: The aim was to compare the diagnostic performance and handling of dynamic contrast-enhanced MRI of the breast with two commercial software solutions ("CADstream" and "3TP") and one self-developed software system ("Mammatool"). MATERIALS AND METHODS: Identical data sets of dynamic breast MRI from 21 patients were evaluated retrospectively with all three software systems. The exams were classified according to the BI-RADS classification. The number of lesions in the parametric mapping was compared to histology or follow-up of more than 2 years. In addition, 25 quality criteria were judged by 3 independent investigators with a score from 0 to 5. Statistical analysis was performed to document the quality ranking of the different software systems. RESULTS: There were 9 invasive carcinomas, one pure DCIS, one papilloma, one radial scar, three histologically proven changes due to mastopathy, one adenosis and two fibroadenomas. Additionally two patients with enhancing parenchyma followed with MRI for more than 3 years and one scar after breast conserving therapy were included. All malignant lesions were classified as BI-RADS 4 or 5 using all software systems and showed significant enhancement in the parametric mapping. "CADstream" showed the best score on subjective quality criteria. "3TP" showed the lowest number of false-positive results. "Mammatool" produced the lowest number of benign tissues indicated with parametric overlay. CONCLUSION: All three software programs tested were adequate for sensitive and efficient assessment of dynamic MRI of the breast. Improvements in specificity may be achievable.
Assuntos
Algoritmos , Neoplasias da Mama/diagnóstico , Mama/patologia , Aumento da Imagem/métodos , Interpretação de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Validação de Programas de Computador , Software , Adulto , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
Pinacidil is a potent antihypertensive agent in animals and humans. In conscious spontaneously hypertensive rats after oral administration, pinacidil was approximately 3- and 10-fold more potent than hydralazine and minoxidil, respectively. Likewise, under in vitro conditions, pinacidil (ED50 = 0.3 microM) was more potent in relaxing serotonin-contracted rat aortic strips than either minoxidil (ED50 = 0.1 mM) or hydralazine (ED50 = 0.2 mM). These data are consistent with the contention that pinacidil is a direct-acting vasodilator whereas minoxidil and hydralazine may be converted in vivo to active moieties and/or exert indirect effects more apparent under in vivo than in vitro conditions. The pharmacology of pinacidil appears unrelated to classical mechanism of vasodilation. Pinacidil does not interact with alpha, beta, cholinergic, or histaminergic receptors. Pinacidil does not produce vasodilation via an indirect effect mediated by adenosine, prostaglandin, or endothelial-derived relaxant factor (EDRF) release. Pinacidil does not alter cAMP or cGMP levels and, based on numerous approaches, does not resemble conventional calcium channel antagonists in its vasodilating activity. Thus, a review of the literature presented herein supports the contention that pinacidil-induced vascular relaxation is a direct effect mediated by a novel mechanism.
Assuntos
Guanidinas/farmacologia , Músculo Liso Vascular/efeitos dos fármacos , Vasodilatação/efeitos dos fármacos , Vasodilatadores/farmacologia , Animais , Anti-Hipertensivos/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Técnicas In Vitro , Masculino , Relaxamento Muscular/efeitos dos fármacos , Pinacidil , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos , Serotonina/farmacologiaRESUMO
We studied the effect of brief periods of left atrial-pulmonary vein distention on the rate of renin secretion in sodium-restricted dogs anesthetized with chloralose and breathing spontaneously. Series 1 consisted of 32 trials in seven dogs with intact renal nerves and intact vagi. Renin secretion, calculated as the product of renal venous minus arterial renin activity (radioimmunoassay) times renal plasma flow (electromagnetic flowmeter), was depressed to 56% of control during atrial distention despite no change in arterial pressure, central venous pressure, or renal blood flow. Series 2 consisted of 58 trials in 12 dogs which had undergone unilateral renal denervation several days prior to the studies. Simultaneous, bilateral determinations indicated that renin secretion from the innervated kidney was depressed to 58% of control during atrial distention; secretion from the denervated kidney was unchanged. Series 3 consisted of 30 trials in six dogs with bilateral cervical vagotomy. Atrial distention evoked no changes in renin secretion. We conclude that left atrial distention reflexly reduces the rates of renin secretion via vagal afferent and renal sympathetic efferent pathways.