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1.
Br J Surg ; 108(12): 1438-1447, 2021 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-34535796

RESUMO

BACKGROUND: Few surgical studies have provided adjusted comparative postoperative outcome data among contemporary patients with and without COVID-19 infection and patients treated before the pandemic. The aim of this study was to determine the impact of performing emergency surgery in patients with concomitant COVID-19 infection. METHODS: Patients who underwent emergency general and gastrointestinal surgery from March to June 2020, and from March to June 2019 in 25 Spanish hospitals were included in a retrospective study (COVID-CIR). The main outcome was 30-day mortality. Secondary outcomes included postoperative complications and failure to rescue (mortality among patients who developed complications). Propensity score-matched comparisons were performed between patients who were positive and those who were negative for COVID-19; and between COVID-19-negative cohorts before and during the pandemic. RESULTS: Some 5307 patients were included in the study (183 COVID-19-positive and 2132 COVID-19-negative during pandemic; 2992 treated before pandemic). During the pandemic, patients with COVID-19 infection had greater 30-day mortality than those without (12.6 versus 4.6 per cent), but this difference was not statistically significant after propensity score matching (odds ratio (OR) 1.58, 95 per cent c.i. 0.88 to 2.74). Those positive for COVID-19 had more complications (41.5 versus 23.9 per cent; OR 1.61, 1.11 to 2.33) and a higher likelihood of failure to rescue (30.3 versus 19.3 per cent; OR 1.10, 0.57 to 2.12). Patients who were negative for COVID-19 during the pandemic had similar rates of 30-day mortality (4.6 versus 3.2 per cent; OR 1.35, 0.98 to 1.86) and complications (23.9 versus 25.2 per cent; OR 0.89, 0.77 to 1.02), but a greater likelihood of failure to rescue (19.3 versus 12.9 per cent; OR 1.56, 95 per cent 1.10 to 2.19) than prepandemic controls. CONCLUSION: Patients with COVID-19 infection undergoing emergency general and gastrointestinal surgery had worse postoperative outcomes than contemporary patients without COVID-19. COVID-19-negative patients operated on during the COVID-19 pandemic had a likelihood of greater failure-to-rescue than prepandemic controls.


Assuntos
Procedimentos Cirúrgicos do Sistema Digestório/mortalidade , Pandemias , Complicações Pós-Operatórias/epidemiologia , Procedimentos Cirúrgicos Operatórios/mortalidade , Adulto , Idoso , COVID-19/epidemiologia , Estudos de Coortes , Emergências , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Espanha/epidemiologia
2.
Transplant Proc ; 43(5): 1871-6, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21693292

RESUMO

BACKGROUND: We analyzed the results of combined heart-kidney transplantation (CHKTx) over a 10-year period. METHODS: Between September 1996 and May 2007 at Mayo Clinic, 12 patients (age 52 ± 12.2 years) underwent CHKTx as a simultaneous procedure in 10 recipients and as a staged procedure in two recipients with unstable hemodynamics after heart transplantation. RESULTS: There was no operative mortality. Patient survival rates for the CHKTx recipients at 1 and 3 months and 6 years were 91%, 83%, and 83% and did not differ from isolated heart transplantation (IHTx) recipients (97%, 95%, and 79%, P = 0.61). The freedom from cardiac allograft rejection (≥ grade 2) at 3 months was 73% for CHKTx and had not changed during further follow-up; for IHTx, freedom from rejection at 3 months and 1 and 6 years was 61%, 56%, and 42% (P = .08). Heart and renal allograft survival was 100% with and left ventricular ejection fraction 66% ± 8.4% and glomerular filtration rate 61 ± 25 at last follow-up. There were no signs of cardiac allograft vasculopathy in the CHKTx recipients. CONCLUSION: CHKTx yields favorable long-term outcome, with a low incidence of cardiac rejection and vasculopathy. Simultaneous CHKTx appears feasible, if hemodynamics is satisfactory. This approach expands the selection criteria for transplantation in patients with coexisting end-stage cardiac and renal disease.


Assuntos
Vasos Coronários/transplante , Rejeição de Enxerto , Transplante de Coração , Transplante de Rim , Adulto , Vasos Coronários/patologia , Feminino , Humanos , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida
3.
Am J Transplant ; 9(1): 132-9, 2009 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19067662

RESUMO

The aim of this study was to assess the patterns, predictors and outcomes of left ventricular remodeling after heart transplantation (HTX). Routine echocardiographic studies were performed and analyzed at 1 week, 1 year and 3-5 years after HTX in 134 recipients. At each study point the total cohort was divided into three subgroups based on determination of left ventricle mass and relative wall thickness: (1) NG-normal geometry (2) CR-concentric remodeling and (3) CH-concentric hypertrophy. Abnormal left ventricular geometry was found as early as 1 week after HTX in 85% of patients. Explosive mode of donor brain death was the most significant determinant of CH (OR 2.9, p = 0.01) at 1 week. CH at 1 week (OR 2.72, p = 0.01), increased body mass index (OR 1.1, p = 0.01) and cytomegalovirus viremia (OR - 4.06, p = 0.02) were predictors of CH at 1 year. CH of the cardiac allograft at 1 year was associated with increased mortality as compared to NG (RR 1.87, p = 0.03). CR (RR 1.73, p = 0.027) and CH (RR 2.04, p = 0.008) of the cardiac allograft at 1 year is associated with increased subsequent graft arteriosclerosis as compared to NG.


Assuntos
Vasos Coronários/fisiopatologia , Transplante de Coração , Taxa de Sobrevida , Remodelação Ventricular , Adulto , Estudos de Coortes , Eletrocardiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transplante Homólogo
4.
Am J Med ; 108(2): 127-35, 2000 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-11126306

RESUMO

PURPOSE: Patients who develop recurrent myocardial ischemia after coronary artery bypass graft (CABG) surgery are often referred for percutaneous coronary interventions. The objective of this study was to evaluate the changing demographic and clinical characteristics, and procedural and long-term outcomes, in patients with prior CABG referred for percutaneous coronary interventions during a 20-year period. METHODS: We prospectively collected data on patients who underwent coronary interventional procedures following CABG surgery. We compared angiographic and procedural success, and long-term event-free survival, among patients who had procedures from 1979 to 1989 (n = 393), from 1990 to 1994 (n = 811), and from 1995 to 1998 (n = 937). RESULTS: Patients in the 1995 to 1998 cohort were older, had a lower mean left ventricular ejection fraction, and were more likely to have diabetes, hypertension, and hyperlipidemia, but less likely to smoke. They were more likely to have treatment of complex lesions, including vein graft lesions, and had more prior CABG surgeries. More patients received intracoronary stents in 1995 to 1998. Both angiographic success rates (78% from 1979 to 1989, 88% from 1990 to 1994, and 91% from 1995 to 1998, P < 0.0001) and procedural success rates (78%, 86%, and 91%, P < 0.0001) improved with time. Long-term mortality was greater in the pre-1990 group (relative risk = 1.8, 95% confidence interval: 1.3 to 2.4) and 1990 to 1994 group (relative risk = 1.7, 95% confidence interval: 1.3 to 2.2) compared with the 1995 to 1998 group, as were the likelihoods of repeat revascularization and recurrent severe angina. CONCLUSION: Although the demographic and clinical characteristics of patients who underwent percutaneous intervention following CABG surgery indicate that they are at increasingly greater risk of adverse cardiac events, success rates and long-term survival have improved with time. The rates of recurrent severe angina as well as of subsequent revascularization have also decreased, probably as a result of improvements in technique and greater use of stents and adjunctive medications.


Assuntos
Angina Instável/terapia , Angioplastia Coronária com Balão , Ponte de Artéria Coronária , Idoso , Angina Instável/diagnóstico por imagem , Angina Instável/tratamento farmacológico , Angina Instável/etiologia , Angina Instável/mortalidade , Angina Instável/cirurgia , Anticoagulantes/uso terapêutico , Angiografia Coronária , Complicações do Diabetes , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Hiperlipidemias/complicações , Hipertensão/complicações , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Recidiva , Reoperação , Fatores de Risco , Índice de Gravidade de Doença , Fumar/efeitos adversos , Stents , Volume Sistólico , Fatores de Tempo , Resultado do Tratamento
5.
Am J Physiol ; 273(2 Pt 2): R838-44, 1997 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-9277577

RESUMO

Chronic thoracic inferior vena caval constriction (TIVCC) is a model of low-cardiac output congestive heart failure (CHF), in which pulmonary and atrial as well as circulating endothelin (ET) are increased. ET is a potent vasoconstrictor and mitogenic peptide whose circulating concentrations are increased in severe human and experimental CHF. To date, an increase in ET production at key sites in CHF remains controversial. Therefore, the current study was designed to determine cardiac and pulmonary ET-1 mRNA in an experimental model of CHF produced by TIVCC in which avid sodium retention, intense vasoconstriction, and elevation of circulating ET-1 occur as in human CHF. Experiments were conducted in normal dogs and dogs with 7 days of TIVCC. Cardiac and pulmonary ET-1 mRNA were measured by quantified densitometry of Northern blots. Plasma and tissue (cardiac and pulmonary) ET-1 immunoreactivity were determined by radioimmunoassay. Cardiac and pulmonary tissue localization of ET-1 were determined by immunohistochemical staining. Plasma ET-1 was significantly increased in TIVCC compared with normal dogs. ET-1 mRNA was detectable in normal canine atria, ventricle, and lung. ET-1 mRNA was significantly increased in TIVCC compared with normal dogs in both atrial and pulmonary tissues without alternations in ventricular ET mRNA. Atrial and pulmonary tissue concentrations of ET-1 also were markedly elevated in TIVCC compared with normal dogs. Immunohistochemical staining of atrial and pulmonary tissues for ET-1 demonstrated that the increased ET immunoreactivity was localized to atrial myocytes and pulmonary epithelial cells. These studies support a role for the heart and lung in the increased production of ET-1 in CHF. The current studies also suggest that ET-1 may have important autocrine and paracrine actions in cardiopulmonary regulation in experimental CHF.


Assuntos
Baixo Débito Cardíaco/metabolismo , Endotelinas/genética , Pulmão/metabolismo , Miocárdio/metabolismo , RNA Mensageiro/metabolismo , Animais , Northern Blotting , Fenômenos Fisiológicos Cardiovasculares , Doença Crônica , Cães , Endotelinas/metabolismo , Átrios do Coração , Hemodinâmica , Imuno-Histoquímica/métodos , Masculino , Concentração Osmolar , Coloração e Rotulagem
6.
Hypertension ; 30(2 Pt 1): 184-90, 1997 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-9260978

RESUMO

C-type natriuretic peptide (CNP) is a newly described 22-amino acid peptide of endothelial and renal cell origin with selective cardiovascular actions. Recent in vitro studies have reported that CNP is the most susceptible of all natriuretic peptides to enzymatic degradation by neutral endopeptidase 24.11 (NEP). The present study was undertaken to define the role of NEP in total and regional CNP metabolism and the modulatory actions of NEP inhibition on the biological actions of CNP. CNP (10 ng x kg(-1) x min(-1)) followed by candoxatrilat (240 microg x kg(-1) bolus and 8 microg x kg(-1) x min(-1)), a potent and selective NEP inhibitor, was administered intravenously to a group of anesthetized mongrel dogs (group 1) to permit calculation of total metabolic clearance rate (MCR); results were compared with those in a group receiving vehicle infusion followed by candoxatrilat (group 2; both groups, n=7). NEP inhibition increased circulating CNP achieved by exogenous infusion and reduced total MCR in group 1. The regional CNP MCRs increased after CNP administration. While the pulmonary MCR did not change during concomitant candoxatrilat infusion, renal MCR was suppressed. Hemodynamic changes were not different between groups. A mild natriuretic and diuretic effect in association with an increase in circulating and urinary ANP levels was not different between groups. Urinary CNP excretion did not change with CNP infusion but markedly increased after NEP inhibition. We conclude that (1) circulating CNP achieved by exogenous CNP infusion is regulated by NEP in vivo, (2) regional MCRs are heterogeneous with NEP inhibition, (3) NEP inhibition does not potentiate acute cardiovascular actions of CNP, and (4) a mild natriuretic and diuretic effect observed with CNP and NEP inhibition may be ANP dependent.


Assuntos
Neprilisina/fisiologia , Proteínas/metabolismo , Animais , Diurese , Cães , Hemodinâmica , Hormônios/sangue , Masculino , Natriurese , Peptídeo Natriurético Tipo C , Proteínas/antagonistas & inibidores , Circulação Renal
7.
J Clin Invest ; 97(5): 1286-92, 1996 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-8636441

RESUMO

Endothelin (ET) is a potent vasoconstrictor peptide which is elevated in plasma in congestive heart failure. Recent studies suggest an important role for angiotensin II (AII) in the activation of ET in cultured cardiomyocytes. Chronic thoracic inferior vena caval constriction (TIVCC) is a model of reduced cardiac output that mimics the neurohumoral activation observed in congestive heart failure. We hypothesized that activation of the renin-angiotensin system in TIVCC plays a role in the activation of ET and that the elevation of endogenous ET contributes to the systemic and renal vasoconstriction that characterizes this model of venous congestion. We studied conscious dogs after 7 d of TIVCC in the presence or absence of chronic angiotensin converting enzyme inhibition with enalapril. TIVCC resulted in marked activation of plasma AII and ET in plasma, right atrium, lung, and renal medulla which was further localized to cardiomyocytes, pulmonary, and renal epithelial cells. Chronic angiotensin converting enzyme inhibition abolished the increases in plasma AII and ET during TIVCC. Acute endothelin A receptor blockade with FR-139317 resulted in significant decreases in mean arterial pressure and systemic vascular resistance in TIVCC. We conclude that activation of the renin-angiotensin system contributes to the activation of circulating and local ET in TIVCC and that this activation plays an important role in the regulation of arterial pressure and systemic vascular resistance in this model of congestive failure.


Assuntos
Inibidores da Enzima Conversora de Angiotensina/farmacologia , Endotelinas/metabolismo , Insuficiência Cardíaca/metabolismo , Animais , Azepinas/farmacologia , Modelos Animais de Doenças , Cães , Hemodinâmica/efeitos dos fármacos , Indóis/farmacologia , Masculino , Veia Cava Inferior
8.
Am J Physiol ; 268(3 Pt 2): F455-60, 1995 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-7900845

RESUMO

Endothelin (ET) is a potent vasoconstrictor peptide of endothelial origin, which at low doses results in renal vasoconstriction and diuresis with variable actions on sodium excretion. The current study conducted in four groups of anesthetized dogs was designed to define the role of the ETA and ETB receptor subtypes in the renal actions of low-dose exogenous ET. Group 1 (n = 4) animals served as time controls. In group 2 (n = 6) a systemic ET-1 (5 ng.kg-1.min-1) infusion mediated renal vasoconstriction, antinatriuresis with increases in proximal fractional reabsorption of sodium, and diuresis with a decrease in urine osmolality. In group 3 (n = 6) intrarenal BQ-123 (4 micrograms.kg-1.min-1), a selective ETA antagonist, abolished the systemic ET-1-mediated changes in renal hemodynamics and unmasked a natriuretic action at the level of the proximal tubule. In contrast, the diuretic response of ET was not altered by BQ-123. In group 4 (n = 6) intrarenal sarafotoxin 6-c, a selective ETB receptor agonist, resulted in a diuretic response without a change in sodium excretion. These studies suggest that the ETA receptor contributes to the renal vasoconstriction, whereas the ETB receptor is largely responsible for the diuretic response during exogenous ET. This study also suggests that at low doses ET is natriuretic in vivo by decreasing proximal tubular reabsorption of sodium independent of ETA or ETB receptor activation.


Assuntos
Rim/fisiologia , Receptores de Endotelina/classificação , Receptores de Endotelina/fisiologia , Animais , Fenômenos Fisiológicos Cardiovasculares , Sistema Cardiovascular/efeitos dos fármacos , Diurese/efeitos dos fármacos , Diurese/fisiologia , Cães , Endotelinas/farmacologia , Rim/efeitos dos fármacos , Masculino , Natriurese/efeitos dos fármacos , Natriurese/fisiologia , Peptídeos Cíclicos/farmacologia , Receptores de Endotelina/efeitos dos fármacos , Circulação Renal/efeitos dos fármacos , Circulação Renal/fisiologia , Vasoconstrição/efeitos dos fármacos , Vasoconstrição/fisiologia , Venenos de Víboras/farmacologia
9.
Am J Physiol ; 267(6 Pt 2): R1653-7, 1994 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-7810777

RESUMO

C-type natriuretic peptide (CNP) is a vasoactive and antimitogenic peptide that is structurally similar but genetically distinct from atrial natriuretic peptide. While first discovered in the brain, CNP has been shown to be produced by endothelial cells and may function in a paracrine and autocrine fashion in the control of vascular tone. Recently, CNP immunoreactivity and B-type natriuretic peptide receptors (NPR-B), for which CNP is a specific ligand, have been identified in the kidney. The present study was designed to determine whether renal epithelial cells produce and secrete CNP and whether CNP immunoreactivity is present in canine kidney. Opossum kidney (OK) cells that express proximal tubular cell characteristics were incubated for 6 h in fetal calf serum-free Dulbecco's modified Eagle's medium (DMEM). CNP immunoreactivity was measured in the preincubation and 6-h conditioned media by radioimmunoassay (RIA) using a specific antibody to CNP-22. Furthermore the molecular form of this CNP-like protein was determined by reverse-phase high-performance liquid chromatography (HPLC), and intracellular localization of the CNP immunoreactivity was determined by immunohistochemical staining. CNP immunoreactivity was also determined in renal tissue from dogs subjected to saline or endothelin infusion. Six-hour incubation in DMEM resulted in accumulation of CNP immunoreactivity (baseline below detection level vs. 6 h = 117.3 +/- 8.3 pg/ml, P < 0.001). Intracellular CNP concentration determined after sonication was 1.9 +/- 0.2 micrograms/g protein, and immunohistochemical staining for CNP was markedly positive in the cytoplasm.(ABSTRACT TRUNCATED AT 250 WORDS)


Assuntos
Túbulos Renais/química , Rim/metabolismo , Proteínas/análise , Proteínas/metabolismo , Animais , Células Cultivadas , Cromatografia Líquida de Alta Pressão , Meios de Cultivo Condicionados , Citoplasma/química , Cães , Endotelinas/farmacologia , Epitélio/metabolismo , Imuno-Histoquímica , Peptídeo Natriurético Tipo C , Gambás
10.
J Hypertens Suppl ; 12(4): S43-9, 1994 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-7965274

RESUMO

PURPOSE: Experiments were designed to determine whether angiotensin converting enzyme inhibition with quinaprilat can prevent endothelin-mediated decreases in renal blood flow and the glomerular filtration rate in the anesthetized dog. METHODS: To mimic the activation of the renal endothelin system that occurs in a number of cardiorenal disease states, endothelin was administered intrarenally in a group of mongrel dogs. Quinaprilat, the major active metabolite of quinapril, was infused in a separate group. One kidney (group 1) or both kidneys (group 2) were exposed in order to measure renal blood flow by an electromagnetic flow probe. Mean arterial blood pressure was measured through a catheter in a femoral vein. Blood samples were taken to determine plasma renin activity. Urine was collected. RESULTS: The infusion of endothelin decreased renal blood flow and the glomerular filtration rate and increased renal vascular resistance. These renal vascular responses were associated with increased plasma renin activity, indicating activation of the renal renin-angiotensin system. Quinaprilat attenuated the renal vascular responses. CONCLUSIONS: These studies provide further evidence of the importance of the renal renin-angiotensin system in mediating the renal vasoconstrictor actions of endothelin and indicate the therapeutic potential for quinapril in opposing the actions of endothelin in states of excessive endothelin activation.


Assuntos
Endotelinas/farmacologia , Circulação Renal/efeitos dos fármacos , Sistema Renina-Angiotensina , Tetra-Hidroisoquinolinas , Vasoconstrição , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Animais , Cães , Endotelinas/uso terapêutico , Hemodinâmica/efeitos dos fármacos , Isoquinolinas/farmacologia
11.
J Am Soc Nephrol ; 4(11): 1920-4, 1994 May.
Artigo em Inglês | MEDLINE | ID: mdl-7919145

RESUMO

Endothelin (ET) is a potent vasoconstrictor peptide of endothelial cell origin. Recent studies have suggested a nonvascular paracrine and/or autocrine role for endothelin in the kidney. This study was designed to elucidate the renal ET response to acute moderate hypoxia, as reflected by urinary ET excretory rate and renal tissue ET immunoreactivity, and to correlate these responses to the hemodynamic and excretory changes during hypoxia. Experiments were conducted in two groups of anesthetized dogs: hypoxic group (10% O2 ventilation: PO2, 44 mm Hg; N = 7) and time control group (room air ventilation: PO2, 111 mm Hg; N = 6). After 60 min of hypoxia or room air ventilation, kidneys were harvested and stained immunohistochemically for ET. Acute moderate hypoxia was associated with significant increases in urinary ET excretion, urine flow, urinary sodium excretion, and fractional excretion of sodium (P < 0.05). There was no significant change in GFR, RBF, renal vascular resistance, or mean arterial pressure. Renal immunohistochemistry for ET revealed increased staining in the proximal and distal tubules in the hypoxic group as compared with controls. This study demonstrates that acute moderate hypoxia results in increased urinary ET excretion and renal tubular ET immunoreactivity, in association with diuresis and natriuresis, and suggests a nonvascular role of endogenously produced renal ET in the regulation of sodium homeostasis during hypoxia.


Assuntos
Endotelinas/metabolismo , Hipóxia/metabolismo , Rim/metabolismo , Animais , Modelos Animais de Doenças , Cães , Endotelinas/sangue , Endotelinas/urina , Homeostase , Hipóxia/sangue , Hipóxia/urina , Imuno-Histoquímica , Córtex Renal/metabolismo , Córtex Renal/patologia , Medula Renal/metabolismo , Medula Renal/patologia , Sódio/metabolismo
12.
Curr Opin Nephrol Hypertens ; 3(1): 66-72, 1994 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-7850414

RESUMO

Endothelin is an important modulator of renal function via its binding to abundant receptors in renal tissue and by the ability of renal endothelial and epithelial cells to synthesize and release endothelin. In the kidney, endothelin may function as a paracrine-autocrine factor in the regulation of renal blood flow, glomerular hemodynamics, and sodium and water homeostasis. Recent evidence suggests that circulating endothelin may play an important role in renal regulation in cardiorenal states of endothelin activation. Endothelin is a potent renal vasconstrictor that has dual actions on glomerular filtration rate due to its ability to preferentially constrict efferent arterioles preserving glomerular filtration. Furthermore, endothelin modulates sodium excretion and water balance at the level of the proximal tubule and medullary collecting ducts, respectively, by mechanisms that are still unclear. In addition, endothelin stimulates the renin-angiotensin-aldosterone system and atrial natriuretic peptide release and inhibits arginine vasopressin-mediated water reabsorption in the inner medullary collecting duct. Recent studies using specific receptor antagonists have demonstrated a pathophysiologic role for endothelin during renal ischemia, cyclosporine-induced toxicity, and chronic renal failure. This review highlights recent research that supports an important role for endothelin as a locally produced vasoactive and natriuretic peptide in the regulation of renal hemodynamic and excretory functions.


Assuntos
Endotelinas/fisiologia , Nefropatias/fisiopatologia , Rim/fisiologia , Rim/fisiopatologia , Injúria Renal Aguda/fisiopatologia , Animais , Água Corporal/metabolismo , Ciclosporina/toxicidade , Endotelinas/biossíntese , Taxa de Filtração Glomerular , Insuficiência Cardíaca/fisiopatologia , Hemodinâmica , Homeostase , Humanos , Rim/efeitos dos fármacos , Falência Renal Crônica/fisiopatologia , Glomérulos Renais/fisiologia , Lesões por Radiação/fisiopatologia , Receptores de Endotelina/fisiologia , Circulação Renal , Sódio/metabolismo
13.
Am J Physiol ; 265(6 Pt 2): R1416-22, 1993 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-8285286

RESUMO

Brain natriuretic peptide (BNP) shares structural and functional similarities to atrial natriuretic peptide (ANP). Although BNP and ANP interact with the same biologically active guanylate cyclase-coupled receptor, recent reports conflict with regard to the biological actions of exogenous BNP in sodium-retaining and edematous states. We studied the biological actions of BNP in normal dogs (n = 5) and sodium-avid dogs with chronic thoracic inferior vena caval constriction (TIVCC) (n = 6). In normal dogs BNP increased glomerular filtration rate, renal blood flow, and urinary sodium excretion and decreased proximal and distal fractional reabsorption of sodium with activation of urinary guanosine 3',5'-cyclic monophosphate (cGMP). These renal actions occurred in association with marked hypotensive actions and activation of systemic cGMP. In TIVCC, a state characterized by chronic reductions of cardiac output, avid sodium retention, edema, and activation of the renin-angiotensin-aldosterone system (RAAS), the renal actions of BNP were absent in association with marked attenuation of the urinary cGMP response. In contrast, an enhanced hypotensive response with preserved activation of systemic cGMP was observed. In neither normal dogs nor TIVCC dogs did BNP inhibit the RAAS. These studies report that BNP is a potent vasoactive and natriuretic peptide with potent proximal and distal tubular actions in normal dogs. These studies also demonstrate that in TIVCC, a model of low cardiac output and congestive failure that results in marked sodium retention with edema in which there is activation of the RAAS, the renal actions of BNP are attenuated while the vasoactive actions are enhanced.


Assuntos
Baixo Débito Cardíaco/fisiopatologia , Insuficiência Cardíaca/fisiopatologia , Proteínas do Tecido Nervoso/farmacologia , Absorção , Animais , Sistema Cardiovascular/efeitos dos fármacos , Constrição , GMP Cíclico/metabolismo , Cães , Taxa de Filtração Glomerular/efeitos dos fármacos , Túbulos Renais/metabolismo , Masculino , Natriurese/efeitos dos fármacos , Peptídeo Natriurético Encefálico , Circulação Renal/efeitos dos fármacos , Sódio/farmacocinética , Tórax , Veia Cava Inferior/fisiologia
14.
Hypertension ; 22(1): 62-6, 1993 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-8319993

RESUMO

The current study was undertaken to define a biological role for the endothelin-A receptor in a clinically relevant model of altered systemic and renal function produced by suprarenal aortic cross-clamping. This model is associated with profound systemic and renal vasoconstriction, acute renal failure, and a significant increase in circulating endothelin. Studies were performed in three groups of anesthetized mongrel dogs. Group 1 (n = 5) underwent aortic cross-clamping for 1 hour; group 2 (n = 5) underwent aortic cross-clamping for 1 hour in the presence of BQ-123, a specific antagonist of the endothelin-A receptor; group 3 (n = 4) received BQ-123 alone. The marked systemic and renal vasoconstriction associated with aortic cross-clamping in group 1 was markedly attenuated in group 2 in the presence of BQ-123. Unlike the vasoconstrictor response, BQ-123 did not attenuate the decrease in glomerular filtration rate associated with this model. Under unstimulated conditions in group 3, BQ-123 had no actions on systemic or renal hemodynamics. In conclusion, the current study demonstrates that the systemic and renal vasoconstriction associated with aortic cross-clamping are in part mediated through the interaction of endothelin and the endothelin-A receptor. This study demonstrates the functional importance of increased endogenous endothelin in the regulation of vascular tone in this pathophysiological state.


Assuntos
Aorta/fisiologia , Rim/irrigação sanguínea , Receptores de Endotelina/fisiologia , Vasoconstrição/fisiologia , Animais , Pressão Sanguínea/efeitos dos fármacos , Débito Cardíaco , Modelos Animais de Doenças , Cães , Endotelinas/sangue , Frequência Cardíaca , Hemodinâmica/efeitos dos fármacos , Isquemia/fisiopatologia , Rim/efeitos dos fármacos , Rim/fisiologia , Isquemia Miocárdica/fisiopatologia , Peptídeos Cíclicos/farmacologia , Receptor de Endotelina A , Resistência Vascular
15.
Am J Physiol ; 264(2 Pt 2): R290-5, 1993 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-8383462

RESUMO

Studies were performed in three groups of anesthetized dogs to compare the structurally related peptides atrial natriuretic peptide (ANP) and C-type natriuretic peptide (CNP). Group 1 (n = 5) and group 2 (n = 4) received intravenous infusions of CNP or ANP respectively at doses of 10 ng.kg-1.min-1 and 100 ng.kg-1.min-1. Group 3 (n = 5) received CNP intrarenally at doses of 1 ng.kg-1.min-1 and 5 ng.kg-1.min-1. Intravenous infusion of CNP resulted in a greater decrease in blood pressure when compared with ANP. This marked decrease in blood pressure observed with CNP was associated with a significantly smaller increase in guanosine 3',5'-cyclic monophosphate (cGMP). In contrast, neither intravenous nor intrarenal administration of CNP was associated with natriuresis as observed with ANP. The current study also demonstrates the presence of CNP immunoreactivity in canine plasma at low picomolar concentrations. Further characterization by gel permeation chromatography demonstrated that circulating CNP immunoreactivity corresponds to the 22-amino acid form of the peptide. In conclusion, this study demonstrates that CNP circulates in low picomolar concentrations and is potently vasoactive in vivo, suggesting a potential role in the regulation of vascular tone.


Assuntos
Fenômenos Fisiológicos Cardiovasculares , Proteínas do Tecido Nervoso/fisiologia , Animais , Fator Natriurético Atrial/farmacologia , Fator Natriurético Atrial/fisiologia , Sangue/metabolismo , Pressão Sanguínea/efeitos dos fármacos , Sistema Cardiovascular/efeitos dos fármacos , Cromatografia em Gel , GMP Cíclico/sangue , GMP Cíclico/metabolismo , Cães , Hemodinâmica/efeitos dos fármacos , Hormônios/sangue , Rim/metabolismo , Masculino , Natriurese/efeitos dos fármacos , Peptídeo Natriurético Tipo C , Proteínas do Tecido Nervoso/farmacologia , Circulação Renal/efeitos dos fármacos
16.
Am J Physiol ; 263(4 Pt 2): H1318-21, 1992 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-1384363

RESUMO

The present study was undertaken to investigate the presence of C-type natriuretic peptide (CNP) immunoreactivity in cultured human vascular endothelial cells and in human plasma. CNP immunoreactivity was present in cultured human aortic endothelial cells by both immunohistochemical staining and by radioimmunoassay. With the utilization of gel permeation chromatography, this immunoreactivity proved to be consistent with the higher molecular weight CNP-53. CNP immunoreactivity was also present in human plasma (n = 22) at low picogram concentrations (6.5 +/- 0.2 pg/ml) by specific radioimmunoassay. This immunoreactivity was consistent with the lower molecular weight CNP-22 by gel permeation chromatography. These findings suggest that the vascular endothelium may be the site of CNP production. The isolation of different molecular forms of CNP in tissue and plasma may be consistent with a storage form of the peptide in endothelial cells CNP-53, while CNP-22 circulates in plasma. In summary, the present study is consistent with CNP being a peptide of endothelial cell origin.


Assuntos
Endotélio Vascular/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Aorta/citologia , Aorta/metabolismo , Fator Natriurético Atrial/sangue , Fator Natriurético Atrial/metabolismo , Células Cultivadas , Cromatografia em Gel , Endotélio Vascular/citologia , Humanos , Imuno-Histoquímica/métodos , Peptídeo Natriurético Tipo C , Proteínas do Tecido Nervoso/sangue , Radioimunoensaio , Coloração e Rotulagem
17.
Peptides ; 13(5): 1017-9, 1992.
Artigo em Inglês | MEDLINE | ID: mdl-1480508

RESUMO

The present study was undertaken to determine the presence of CNP immunoreactivity in human breast tissue (n = 9). Immunohistochemical staining of breast tissue revealed the presence of CNP immunoreactivity localized to vascular endothelial cells. This study demonstrates for the first time that CNP immunoreactivity is present in humans. Based upon the knows biological actions of CNP, these findings suggest that CNP may function as part of an endothelium-derived vasoregulatory system.


Assuntos
Fator Natriurético Atrial/metabolismo , Mama/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Mama/irrigação sanguínea , Endotélio Vascular/metabolismo , Feminino , Humanos , Imuno-Histoquímica , Peptídeo Natriurético Tipo C
18.
Am J Physiol ; 262(1 Pt 2): H308-12, 1992 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-1310235

RESUMO

Studies were performed in two groups of anesthetized dogs (n = 5 per group) to determine the cardiovascular and renal actions of synthetic C-type natriuretic peptide (CNP). Systemic infusion of CNP (group 1; 10 and 50 ng.kg-1.min-1 iv) resulted in marked cardiovascular hemodynamic effects characterized by a decrease in mean arterial pressure, cardiac output, and atrial pressures in association with a decrease in sodium excretion. Bolus administration of CNP (group 2; 5 micrograms/kg iv) to minimize cardiovascular hemodynamic changes resulted in only a transient decrease in arterial pressure. Sodium excretion decreased despite a return of arterial pressure to baseline. These biological responses were associated with increases in plasma guanosine 3',5'-cyclic monophosphate (cGMP) in both groups but with no change in urinary cGMP. With both systemic infusion or bolus administration of CNP, significant increases in plasma aldosterone were observed in association with increases in distal nephron sodium reabsorption. This study demonstrates that CNP exhibits profound systemic hemodynamic actions and is indirectly, or perhaps directly, antinatriuretic.


Assuntos
Sistema Cardiovascular/efeitos dos fármacos , Rim/efeitos dos fármacos , Proteínas do Tecido Nervoso/farmacologia , Absorção , Animais , Pressão Sanguínea/efeitos dos fármacos , Débito Cardíaco/efeitos dos fármacos , GMP Cíclico/sangue , Cães , Taxa de Filtração Glomerular/efeitos dos fármacos , Túbulos Renais Proximais/metabolismo , Masculino , Peptídeo Natriurético Tipo C , Circulação Renal/efeitos dos fármacos , Sódio/metabolismo , Resistência Vascular/efeitos dos fármacos
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